A Study to Characterize the Abuse Liability of ALO-02 in Healthy, Non-Dependent, Recreational Opioid Abusers

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01746901
• Collaborator: Syneos Health (Other)
• Enrollment: 81
• Location: 1
• Arms: 6
• Actual Duration (Months): 6.2
• Patients Per Site Per Month: 13

Study Details

Study Description

Brief Summary

The main purpose of this study is to determine if oxycodone and naltrexone combination capsules (ALO-02) have the potential to be abused.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Placebo; Drug: intact ALO-02 60 mg/7.2 mg; Drug: crushed ALO-02 60 mg/7.2 mg; Drug: crushed oxycodone IR 60 mg; Drug: crushed ALO-02 40 mg/4.8 mg; Drug: crushed oxycodone IR 40 mg	Phase 1

Detailed Description

Abuse Liability Study

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: A Randomized, Double-blind, Double-dummy, Placebo Controlled, Single-dose, 6-way Crossover Study To Determine The Relative Abuse Potential Of Alo-02 (Oxycodone Hydrochloride And Naltrexone Hydrochloride Extended-release Capsules) Compared To Oxycodone Immediate Release And Placebo When Administered Orally To Nondependent,Recreational Opioid Users.
• Actual Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Aug 9, 2013
• Actual Study Completion Date: Aug 9, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Treatment A	Drug: Placebo; Placebo solution + Placebo ALO-02 (intact)
Experimental: Treatment B	Drug: intact ALO-02 60 mg/7.2 mg; Placebo solution + ALO-02 60 mg/7.2 mg (intact)
Experimental: Treatment C	Drug: crushed ALO-02 60 mg/7.2 mg; crushed ALO-02 60 mg/7.2 mg in solution + placebo ALO-02 (intact)
Active Comparator: Treatment D	Drug: crushed oxycodone IR 60 mg; crushed oxycodone immediate-release (IR) 60 mg in solution + placebo ALO-02 (intact)
Experimental: Treatment E	Drug: crushed ALO-02 40 mg/4.8 mg; crushed ALO-02 40 mg/4.8 mg in solution + placebo ALO-02 (intact)
Active Comparator: Treatment F	Drug: crushed oxycodone IR 40 mg; crushed oxycodone immediate-release (IR) 40 mg in solution + placebo ALO-02 (intact)

Outcome Measures

Primary Outcome Measures

1. Drug Liking: Peak Effect (Emax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase]

   Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the extreme left with "strong disliking" (score of 0 mm) and on the extreme right with "strong liking" (score of 100 mm). Peak Effect (Emax) = Maximum observed score.

2. Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour [0.25, 0.5, 1, 1.5, 2 hours post-dose]

   Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the extreme left with "strong disliking" (score of 0 mm) and on the extreme right with "strong liking" (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.

3. High: Peak Effect (Emax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase]

   High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

4. High: Area Under Effect Curve (AUE) From 0-2 Hour [pre-dose, 0.25, 0.5, 1, 1.5, 2 hours post-dose]

   High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.

Secondary Outcome Measures

1. Take Drug Again: Peak Effect (Emax) [12, 24, 36 hours post-dose]

   Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

2. Take Drug Again: Mean Effect (Emean) [12, 24, 36 hours post-dose]

   Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

3. Take Drug Again: Minimum Effect (Emin) [12, 24, 36 hours post-dose]

   Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

4. Take Drug Again Effect at Hours 12, 24 and 36 [12, 24, 36 hours post-dose]

   Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.

5. Overall Drug Liking: Peak Effect (Emax) [12, 24, 36 hours post-dose]

   Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emax = Maximum observed score.

6. Overall Drug Liking: Mean Effect (Emean) [12, 24, 36 hours post-dose]

   Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emean = Average observed score.

7. Overall Drug Liking: Minimum Effect (Emin) [12, 24, 36 hours post-dose]

   Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emin= Average observed score.

8. Overall Drug Liking Effect at Hours 12, 24 and 36 [12, 24, 36 hours post-dose]

   Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking").

9. Any Drug Effects: Peak Effect (Emax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

10. Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

11. Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

12. Good Drug Effects: Peak Effect (Emax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

13. Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

14. Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

15. Bad Drug Effects: Peak Effect (Emax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

16. Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

17. Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

18. Feel Sick: Peak Effect (Emax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

19. Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

20. Feel Sick: Time to Maximum (Peak) Effect (TEmax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

21. Nausea: Peak Effect (Emax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

22. Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

23. Nausea: Time to Maximum (Peak) Effect (TEmax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

24. Sleepy: Peak Effect (Emax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

25. Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

26. Sleepy: Time to Maximum (Peak) Effect (TEmax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm)to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

27. Dizzy: Peak Effect (Emax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.

28. Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

29. Dizzy: Time to Maximum (Peak) Effect (TEmax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

30. Pupillometry: Peak Effect (Emax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. Emax = Maximum observed score.

31. Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).

32. Pupillometry: Time to Maximum (Peak) Effect (TEmax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. TEmax = Time to maximum observed score.

33. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.

Other Outcome Measures

1. Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).

2. Drug Liking: Time to Maximum (Peak) Effect (TEmax) [0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). TEmax = Time to maximum observed score.

3. High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).

4. High: Time to Maximum (Peak) Effect (TEmax) [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.

5. Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   Cmax[dn]=Dose normalized maximum observed plasma concentration of participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.

6. Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.

7. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.

8. Plasma Terminal Half-Life (t1/2) of Oxycodone [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.

9. Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

   AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Participants who received oxycodone were reported.

10. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    Area under the plasma concentration time-curve from zero to the last quantifiable concentration (AUClast). Participants who received oxycodone were reported.

11. Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone [pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose]

    [AUC (0 - ∞)dn]= Dose normalized area under the plasma concentration versus time curve [AUC(dn)] from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0- t) plus AUC (t - ∞). Participants who received oxycodone were reported. Participants who received oxycodone were reported.

12. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Screening up to 28 days after last study drug administration (Day 29)]

    An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 3 - 7 days following last study drug administration. Symptoms of withdrawal following naloxone administration (naloxone challenge phase) were not collected as adverse events unless they met the criteria for an SAE. AEs included SAEs as well as non-serious AEs which occurred during the trial.

13. Number of Participants With Clinically Significant Change in Vital Sign Examinations [Screening up to 7 days following last study drug administration (Day 8)]

    Vital signs assessment included measurement of heart rate, systolic and diastolic blood pressures, respiratory rate and oral temperature. Criteria for clinically significant change in any vital sign examination was based on investigator's discretion.

14. Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2) [pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5 hours post-dose in drug discrimination phase; pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in intervention period]

    End-tidal carbon dioxide concentration in the expired air (EtCO2) was monitored using capnography in a sitting position. Criteria for clinically significant change in EtCO2 was based on investigator's discretion.

15. Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2) [pre-dose up to 5 hours in drug discrimination phase; pre-dose up to 12 hours in intervention period]

    Oxygen saturation of hemoglobin in blood (SpO2) was monitored using pulse oximetry continuously for 5 hours following dosing in the drug discrimination phase and continuously for 12 hours following dosing in the treatment phase, or longer at the discretion of the investigator. Individual measurements was collected in a sitting position. If SpO2 fall below 90 percent (%), the investigator might had administered oxygen via nasal cannula at a flow rate sufficient to maintain the SpO2 greater than or equal to 90%. Participants with fall in SpO2 below 90% were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy subjects.

• Non-dependent, recreational opioid users. (Must use opioid for non-therapeutic purposes on at least 10 occassions within the last year before Screening Visit, and at least once in 8 weeks before the Screening Visit.

Exclusion Criteria:

• Diagnosis of substance and/or alcohol dependence.

• Subject has participated in, is currently participating in, or is seeking treatment for substance and/or alcohol related disorder.

• History of sleep apnea.

• Positive urine drug screen (UDS) for other that marijuana.

• Positive for Hepatitis B or C and HIV on Screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	INC Research Toronto, Inc.	Toronto	Ontario	Canada	M5V 2T3

Sponsors and Collaborators

• Pfizer
• Syneos Health

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01746901
• Other Study ID Numbers: B4531008
• First Posted: Dec 11, 2012
• Last Update Posted: Oct 19, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Pfizer: Relative abuse potential study; oxycodone; nalteone; Opioid-related disorders; drug abusers; Chronic pain
• Additional relevant MeSH terms: Naltrexone; Oxycodone

Study Results

Participant Flow

Recruitment Details	Recreational opioid users who were not dependent on opioids based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria, were recruited in this study.
Pre-assignment Detail	After successful naloxone challenge test, all participants underwent training sessions involving complete pharmacodynamics test battery before the drug discrimination phase, to ensure that participants fully understood how to perform the tests, were comfortable, and attained a stable level of performance on the various performance-based measures.

Arm/Group Title	Naloxone	Oxycodone HCl 40 mg Then PBO	PBO Then Oxycodone HCl 40 mg	ALO-02 60 Mg-I,ALO-02 60 Mg-C,PBO,OXY 60,40 mg,ALO-02 40 Mg-C	ALO-02 40 Mg-C,OXY 40,60 mg,PBO,ALO-02 60 Mg-C,ALO-02 60 Mg-I	ALO-02 60 Mg-C,OXY 60 mg,ALO-02 60 Mg-I,40 Mg-C,PBO,OXY40 mg	OXY 40 mg,PBO,ALO-02 40 Mg-C,60 Mg-I,OXY 60 mg,ALO-02 60 Mg-C	OXY 60 mg,ALO-02 40, 60 Mg-C,OXY 40 mg,ALO-02 60 Mg-I,PBO	PBO,ALO-02 60 Mg-I,OXY 40 mg, ALO-02 60, 40 Mg-C,OXY 60 mg
Arm/Group Description	Naloxone hydrochloride (HCl) 0.2 milligram (mg) intravenously followed by additional 0.6 mg naloxone hydrochloride intravenously on Day 0, each dose followed by an assessment for signs and symptoms of opioid withdrawal. Participants who did not display signs and symptoms of opioid withdrawal, were assigned to either oxycodone HCl 40 mg then placebo or placebo then oxycodone HCl 40 mg group in the drug discrimination phase of the study.	Single dose of oxycodone HCl 40 mg crushed tablet in solution, orally on Day 1 followed by single dose of placebo matched to oxycodone HCl crushed tablet orally on Day 2. Participants were assigned to receive oxycodone HCl 60 mg and naltrexone HCl 7.2 mg extended-release (ALO-02) 60 mg/7.2 mg intact capsule, ALO-02 60 mg/7.2 mg and ALO-02 40 mg/4.8 mg crushed capsule in solution, oxycodone HCl 40 mg (OXY 40 mg) and 60 mg crushed tablet (OXY 60 mg) in solution, placebo matched to either ALO-02 intact (PBO) and crushed capsule or oxycodone crushed tablet (PBO), orally, in either of the 6 sequences in the treatment phase of the study.	Single dose of placebo matched to oxycodone HCl crushed tablet orally on Day 1 followed by single dose of oxycodone HCl 40 mg crushed tablet in solution, orally on Day 2. Participants were assigned to receive oxycodone HCl 60 mg and naltrexone HCl 7.2 mg extended-release (ALO-02) 60 mg/7.2 mg intact capsule, ALO-02 60 mg/7.2 mg and ALO-02 40 mg/4.8 mg crushed capsule in solution, oxycodone HCl 40 mg (OXY 40 mg) and 60 mg crushed tablet (OXY 60 mg) in solution, placebo matched to either ALO-02 intact (PBO) and crushed capsule or oxycodone crushed tablet (PBO), orally, in either of the 6 sequences in the treatment phase of the study.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally on Day 1 in first intervention period; followed by single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally on Day 1 in second intervention period; then single dose of matching placebo (PBO) orally on Day 1 in third intervention period; then single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally on Day 1 in fourth intervention period; then single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally on Day 1 in fifth intervention period; then single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally on Day 1 in sixth intervention period. A washout period of at least 5 days (not exceeding 14 days) was maintained between each intervention period.	Single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally on Day 1 in first intervention period; followed by single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally on orally on Day 1 in second intervention period; then single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally on Day 1 in third intervention period; then single dose of matching placebo (PBO) orally on Day 1 in fourth intervention period; then single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally on Day 1 in fifth intervention period; then single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally on Day 1 in sixth intervention period. A washout period of at least 5 days (not exceeding 14 days) was maintained between each intervention period.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally on Day 1 in first intervention period; followed by single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally on Day 1 in second intervention period; then single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally on Day 1 in third intervention period; then single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally on Day 1 in fourth intervention period; then single dose of matching placebo (PBO) orally on Day 1 in fifth intervention period; then single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally on Day 1 in sixth intervention period. A washout period of at least 5 days (not exceeding 14 days) was maintained between each intervention period.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally on Day 1 in first intervention period; followed by single dose of matching placebo (PBO) orally on Day 1 in second intervention period; then single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally on Day 1 in third intervention period; then single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally on Day 1 in fourth intervention period; then single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally on Day 1 in fifth intervention period; then single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally on Day 1 in sixth intervention period. A washout period of at least 5 days (not exceeding 14 days) was maintained between each intervention period.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally on Day 1 in first intervention period; followed by single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally on Day 1 in second intervention period; then single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally on Day 1 in third intervention period; then single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally on Day 1 in fourth intervention period; then single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally on Day 1 in fifth intervention period; then by single dose of matching placebo (PBO) orally on Day 1 in sixth intervention period. A washout period of at least 5 days (not exceeding 14 days) was maintained between each intervention period.	Single dose of matching placebo (PBO) orally on Day 1 in first intervention period; followed by single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally on Day 1 in second intervention period; then single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally on Day 1 in third intervention period; then single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally on Day 1 in fourth intervention period; then single dose of ALO-02 40 mg/4.8 mg crushed capsule (ALO-02 40 mg-I) solution orally on Day 1 in fifth intervention period; then single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally on Day 1 in sixth intervention period. A washout period of at least 5 days (not exceeding 14 days) was maintained between each intervention period.
Period Title: Naloxone Challenge Phase
STARTED	75	0	0	0	0	0	0	0	0
COMPLETED	72	0	0	0	0	0	0	0	0
NOT COMPLETED	3	0	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	36	36	0	0	0	0	0	0
COMPLETED	0	33	36	0	0	0	0	0	0
NOT COMPLETED	0	3	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	33	36	0	0	0	0	0	0
COMPLETED	0	19	22	0	0	0	0	0	0
NOT COMPLETED	0	14	14	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	6	6	7	8	7	7
COMPLETED	0	0	0	6	6	7	7	7	7
NOT COMPLETED	0	0	0	0	0	0	1	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	6	6	7	7	7	7
COMPLETED	0	0	0	6	6	7	7	7	7
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	6	6	7	7	7	7
COMPLETED	0	0	0	6	6	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0	0	1	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	6	6	7	7	6	7
COMPLETED	0	0	0	6	6	7	7	6	7
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	6	6	7	7	6	7
COMPLETED	0	0	0	6	6	6	6	6	7
NOT COMPLETED	0	0	0	0	0	1	1	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	6	6	6	6	6	7
COMPLETED	0	0	0	6	6	6	6	6	7
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	6	6	6	6	6	7
COMPLETED	0	0	0	5	6	5	5	6	5
NOT COMPLETED	0	0	0	1	0	1	1	0	2
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	5	6	5	5	6	5
COMPLETED	0	0	0	5	6	5	5	6	5
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	5	6	5	5	6	5
COMPLETED	0	0	0	5	6	5	5	6	5
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	5	6	5	5	6	5
COMPLETED	0	0	0	5	6	5	5	6	5
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Naloxone Challenge Phase
STARTED	0	0	0	5	6	5	5	6	5
COMPLETED	0	0	0	5	6	5	5	6	5
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	Included all participants enrolled in the study.
Overall Participants	75
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.6 (9.1)
Sex: Female, Male (Count of Participants)
Female	18 24%
Male	57 76%

Outcome Measures

1. Primary Outcome

Title	Drug Liking: Peak Effect (Emax)
Description	Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the extreme left with "strong disliking" (score of 0 mm) and on the extreme right with "strong liking" (score of 100 mm). Peak Effect (Emax) = Maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose Pharmacodynamic (PD) data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	51.6 (3.74)	70.1 (19.23)	85.5 (16.11)	59.3 (15.09)	74.4 (18.10)	89.7 (13.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	30.5
	Confidence Interval	(2-Sided) 95%; 24.4 to 36.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0132
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; 1.6 to 13.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.3
	Confidence Interval	(2-Sided) 95%; 9.3 to 21.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.9
	Confidence Interval	(2-Sided) 95%; 16.8 to 28.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.3
	Confidence Interval	(2-Sided) 95%; 9.3 to 21.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	18.5
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	18.5
	Confidence Interval	(2-Sided) 95%; 12.5 to 24.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour
Description	Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the extreme left with "strong disliking" (score of 0 mm) and on the extreme right with "strong liking" (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.
Time Frame	0.25, 0.5, 1, 1.5, 2 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [hours*mm]	100.004 (5.1468)	118.480 (28.7707)	141.305 (32.9203)	100.188 (10.6437)	127.320 (31.2906)	149.484 (24.1907)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	49.3
	Confidence Interval	(2-Sided) 95%; 39.2 to 59.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9994
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -10.1 to 10.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.2
	Confidence Interval	(2-Sided) 95%; 12.1 to 32.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	27.1
	Confidence Interval	(2-Sided) 95%; 17.0 to 37.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	23.0
	Confidence Interval	(2-Sided) 95%; 12.8 to 33.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	18.2
	Confidence Interval	(2-Sided) 95%; 8.1 to 28.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	High: Peak Effect (Emax)
Description	High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in treatment phase

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	10.9 (20.60)	47.3 (36.88)	77.9 (25.46)	21.7 (35.36)	53.4 (34.68)	84.7 (23.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	63.2
	Confidence Interval	(2-Sided) 95%; 51.5 to 74.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0402
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.3
	Confidence Interval	(2-Sided) 95%; 0.6 to 24.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.9
	Confidence Interval	(2-Sided) 95%; 21.1 to 44.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	42.6
	Confidence Interval	(2-Sided) 95%; 30.9 to 54.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.1
	Confidence Interval	(2-Sided) 95%; 20.3 to 43.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	36.3
	Confidence Interval	(2-Sided) 95%; 24.6 to 48.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	High: Area Under Effect Curve (AUE) From 0-2 Hour
Description	High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [hours*mm]	2.496 (8.3003)	55.250 (54.1280)	112.082 (43.7000)	9.902 (21.1911)	71.254 (55.9812)	117.578 (42.2152)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	108.0
	Confidence Interval	(2-Sided) 95%; 91.6 to 124.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4125
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95%; -9.6 to 23.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	46.1
	Confidence Interval	(2-Sided) 95%; 29.6 to 62.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	68.8
	Confidence Interval	(2-Sided) 95%; 52.4 to 85.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	56.7
	Confidence Interval	(2-Sided) 95%; 40.3 to 73.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	52.6
	Confidence Interval	(2-Sided) 95%; 36.2 to 69.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Take Drug Again: Peak Effect (Emax)
Description	Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	45.7 (19.05)	57.9 (33.58)	83.4 (20.26)	48.1 (28.14)	72.0 (28.31)	81.3 (25.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 21.8 to 43.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6434
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -8.4 to 13.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1072
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.0
	Confidence Interval	(2-Sided) 95%; -2.0 to 20.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	26.3
	Confidence Interval	(2-Sided) 95%; 15.4 to 37.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25.7
	Confidence Interval	(2-Sided) 95%; 14.7 to 36.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0335
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.9
	Confidence Interval	(2-Sided) 95%; 0.9 to 22.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Take Drug Again: Mean Effect (Emean)
Description	Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	42.90 (20.002)	54.71 (32.635)	77.80 (22.880)	42.63 (26.293)	68.78 (29.883)	78.02 (24.868)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	35.0
	Confidence Interval	(2-Sided) 95%; 24.0 to 46.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9811
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -11.1 to 10.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1083
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.0
	Confidence Interval	(2-Sided) 95%; -2.0 to 19.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25.9
	Confidence Interval	(2-Sided) 95%; 14.9 to 36.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	23.2
	Confidence Interval	(2-Sided) 95%; 12.3 to 34.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0408
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.5
	Confidence Interval	(2-Sided) 95%; 0.5 to 22.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Take Drug Again: Minimum Effect (Emin)
Description	Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	41.1 (21.60)	50.9 (32.46)	73.2 (26.92)	37.8 (28.72)	66.3 (31.57)	75.2 (24.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	36.9
	Confidence Interval	(2-Sided) 95%; 25.2 to 48.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5968
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; -14.9 to 8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1471
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.7
	Confidence Interval	(2-Sided) 95%; -3.1 to 20.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1136
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; -2.3 to 21.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.4
	Confidence Interval	(2-Sided) 95%; 10.6 to 34.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1136
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; -2.3 to 21.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Take Drug Again Effect at Hours 12, 24 and 36
Description	Take drug again VAS is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm VAS with score ranging from 0 mm to 100 mm (score of 0 mm = "definitely would not", 50 mm = "do not care", and 100 mm = "definitely would"). Emax = Maximum observed score.
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Hour 12	44.0 (20.63)	54.7 (33.56)	79.7 (22.37)	45.8 (27.53)	68.7 (30.31)	78.9 (25.21)
Hour 24	41.8 (21.79)	55.5 (32.73)	76.9 (26.77)	41.0 (28.73)	69.6 (28.34)	78.3 (25.17)
Hour 36	42.9 (20.40)	53.9 (32.84)	76.8 (25.12)	41.1 (28.95)	68.1 (31.99)	76.8 (25.17)

9. Secondary Outcome

Title	Overall Drug Liking: Peak Effect (Emax)
Description	Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emax = Maximum observed score.
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	50.8 (12.80)	64.3 (24.00)	80.8 (19.51)	52.9 (21.33)	74.0 (22.44)	81.6 (23.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	28.5
	Confidence Interval	(2-Sided) 95%; 19.6 to 37.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6209
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -6.7 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0997
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.5
	Confidence Interval	(2-Sided) 95%; -1.4 to 16.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	23.2
	Confidence Interval	(2-Sided) 95%; 14.4 to 32.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	16.6
	Confidence Interval	(2-Sided) 95%; 7.7 to 25.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	13.3
	Confidence Interval	(2-Sided) 95%; 4.4 to 22.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Overall Drug Liking: Mean Effect (Emean)
Description	Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emean = Average observed score.
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	50.19 (11.962)	61.26 (24.489)	75.70 (21.304)	47.72 (20.715)	69.94 (23.370)	77.90 (23.077)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	29.9
	Confidence Interval	(2-Sided) 95%; 21.1 to 38.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5951
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -11.2 to 6.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0841
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.8
	Confidence Interval	(2-Sided) 95%; -1.1 to 16.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	19.8
	Confidence Interval	(2-Sided) 95%; 11.0 to 28.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.5
	Confidence Interval	(2-Sided) 95%; 5.7 to 23.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0172
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.8
	Confidence Interval	(2-Sided) 95%; 1.9 to 19.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Overall Drug Liking: Minimum Effect (Emin)
Description	Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking"). Emin= Average observed score.
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	49.6 (11.40)	58.5 (24.82)	71.1 (25.28)	43.6 (23.55)	65.6 (25.87)	74.3 (23.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	30.4
	Confidence Interval	(2-Sided) 95%; 21.0 to 39.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2166
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) 95%; -15.4 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0777
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95%; -1.0 to 18.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	16.0
	Confidence Interval	(2-Sided) 95%; 6.5 to 25.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0086
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.7
	Confidence Interval	(2-Sided) 95%; 3.3 to 22.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0775
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95%; -0.9 to 18.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Overall Drug Liking Effect at Hours 12, 24 and 36
Description	Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = "strong disliking", 50 mm = "neither like nor dislike", and 100 mm= "strong liking").
Time Frame	12, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Hour 12	50.6 (12.78)	61.2 (26.16)	78.5 (20.86)	51.8 (21.57)	69.8 (23.19)	78.1 (23.99)
Hour 24	50.3 (11.84)	62.7 (23.25)	75.5 (24.26)	44.8 (23.62)	70.1 (24.53)	78.1 (22.95)
Hour 36	49.7 (11.41)	59.9 (25.20)	73.2 (25.03)	46.6 (23.35)	69.9 (25.43)	77.6 (23.79)

13. Secondary Outcome

Title	Any Drug Effects: Peak Effect (Emax)
Description	Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	8.8 (19.43)	47.2 (38.45)	82.4 (25.27)	27.7 (35.77)	56.0 (35.90)	88.7 (20.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	61.2
	Confidence Interval	(2-Sided) 95%; 48.8 to 73.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0032
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	18.8
	Confidence Interval	(2-Sided) 95%; 6.4 to 31.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.9
	Confidence Interval	(2-Sided) 95%; 20.5 to 45.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	47.2
	Confidence Interval	(2-Sided) 95%; 34.8 to 59.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	73.6
	Confidence Interval	(2-Sided) 95%; 61.1 to 86.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	38.4
	Confidence Interval	(2-Sided) 95%; 26.0 to 50.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	1.105 (5.6058)	20.129 (23.9971)	40.199 (20.3489)	4.539 (11.9639)	26.566 (24.8693)	48.328 (19.8494)
AUE (0-2)	3.090 (10.1113)	57.504 (57.6543)	112.910 (41.6661)	10.734 (23.0043)	69.059 (55.0442)	124.617 (41.2197)
AUE (0-8)	5.949 (16.4695)	140.152 (147.5551)	283.770 (173.4241)	53.242 (99.4186)	167.137 (152.8249)	354.391 (184.4799)
AUE (0-12)	5.949 (16.4695)	156.652 (175.1035)	317.270 (218.4262)	107.180 (190.7655)	176.199 (165.0887)	392.828 (229.3565)
AUE (0-24)	13.762 (46.7425)	157.059 (175.7028)	345.301 (260.4659)	218.805 (379.7129)	184.137 (172.7494)	402.516 (244.3471)
AUE (0-36)	23.324 (98.1331)	157.059 (175.7028)	345.488 (260.3746)	235.117 (424.9088)	186.387 (173.5877)	402.703 (244.2750)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	43.9
	Confidence Interval	(2-Sided) 95%; 36.0 to 51.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4154
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; -4.6 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	21.8
	Confidence Interval	(2-Sided) 95%; 13.9 to 29.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25.4
	Confidence Interval	(2-Sided) 95%; 17.5 to 33.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	20.2
	Confidence Interval	(2-Sided) 95%; 12.3 to 28.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	18.9
	Confidence Interval	(2-Sided) 95%; 11.0 to 26.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	114.2
	Confidence Interval	(2-Sided) 95%; 97.1 to 131.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3985
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; -9.8 to 24.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	55.6
	Confidence Interval	(2-Sided) 95%; 38.5 to 72.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	65.9
	Confidence Interval	(2-Sided) 95%; 48.8 to 83.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	55.6
	Confidence Interval	(2-Sided) 95%; 38.5 to 72.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	54.1
	Confidence Interval	(2-Sided) 95%; 37.0 to 71.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	302.8
	Confidence Interval	(2-Sided) 95%; 248.8 to 356.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0824
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	47.8
	Confidence Interval	(2-Sided) 95%; -6.2 to 101.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	188.5
	Confidence Interval	(2-Sided) 95%; 134.6 to 242.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	162.0
	Confidence Interval	(2-Sided) 95%; 108.0 to 216.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	141.9
	Confidence Interval	(2-Sided) 95%; 87.9 to 195.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	135.7
	Confidence Interval	(2-Sided) 95%; 81.7 to 189.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	287.6
	Confidence Interval	(2-Sided) 95%; 219.1 to 356.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	101.4
	Confidence Interval	(2-Sided) 95%; 32.9 to 169.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	218.5
	Confidence Interval	(2-Sided) 95%; 150.0 to 287.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	170.5
	Confidence Interval	(2-Sided) 95%; 102.0 to 239.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	158.6
	Confidence Interval	(2-Sided) 95%; 90.1 to 227.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	152.2
	Confidence Interval	(2-Sided) 95%; 83.7 to 220.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	185.9
	Confidence Interval	(2-Sided) 95%; 90.1 to 281.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	205.0
	Confidence Interval	(2-Sided) 95%; 109.2 to 300.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	221.0
	Confidence Interval	(2-Sided) 95%; 125.2 to 316.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	170.0
	Confidence Interval	(2-Sided) 95%; 74.1 to 265.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	185.7
	Confidence Interval	(2-Sided) 95%; 89.9 to 281.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	144.9
	Confidence Interval	(2-Sided) 95%; 49.1 to 240.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	170.0
	Confidence Interval	(2-Sided) 95%; 65.2 to 274.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	211.4
	Confidence Interval	(2-Sided) 95%; 106.6 to 316.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	219.2
	Confidence Interval	(2-Sided) 95%; 114.5 to 324.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	162.2
	Confidence Interval	(2-Sided) 95%; 57.3 to 267.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	185.9
	Confidence Interval	(2-Sided) 95%; 81.1 to 290.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0116
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	135.5
	Confidence Interval	(2-Sided) 95%; 30.7 to 240.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Any Drug Effects: Time to Maximum (Peak) Effect (TEmax)
Description	Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.258	1.017	1.017	0.758	1.258	1.017

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -4.3 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; 1.4 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8440
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.3 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7295
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8757
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.3 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Good Drug Effects: Peak Effect (Emax)
Description	Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	11.6 (24.91)	48.1 (38.53)	81.8 (24.54)	24.2 (34.68)	54.7 (36.16)	84.3 (22.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	60.1
	Confidence Interval	(2-Sided) 95%; 47.4 to 72.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0514
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.6
	Confidence Interval	(2-Sided) 95%; -0.1 to 25.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	29.7
	Confidence Interval	(2-Sided) 95%; 17.0 to 42.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	43.0
	Confidence Interval	(2-Sided) 95%; 30.3 to 55.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	33.7
	Confidence Interval	(2-Sided) 95%; 21.0 to 46.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	36.4
	Confidence Interval	(2-Sided) 95%; 23.7 to 49.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	0.805 (3.6598)	20.727 (23.7958)	40.992 (19.3835)	5.254 (12.3129)	28.234 (25.4785)	44.656 (19.3060)
AUE (0-2)	3.055 (10.0140)	56.352 (55.7819)	110.430 (42.2789)	10.543 (22.1051)	71.305 (58.7340)	114.953 (41.8081)
AUE (0-8)	9.063 (24.0659)	130.758 (152.6257)	261.813 (163.8714)	40.418 (87.9945)	159.750 (156.8189)	332.352 (193.5146)
AUE (0-12)	9.250 (24.0378)	148.195 (183.1627)	282.875 (205.0344)	77.855 (172.2503)	168.688 (173.4909)	372.414 (248.2861)
AUE (0-24)	17.469 (51.3009)	148.883 (183.8413)	297.656 (240.6821)	161.043 (349.4292)	180.875 (212.9759)	380.414 (261.0990)
AUE (0-36)	26.844 (101.2648)	148.883 (183.8413)	297.844 (240.6209)	171.355 (394.6735)	180.875 (212.9759)	380.602 (261.1626)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	39.5
	Confidence Interval	(2-Sided) 95%; 31.8 to 47.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2739
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; -3.4 to 12.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	16.4
	Confidence Interval	(2-Sided) 95%; 8.7 to 24.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	27.4
	Confidence Interval	(2-Sided) 95%; 19.7 to 35.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	20.5
	Confidence Interval	(2-Sided) 95%; 12.8 to 28.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	19.7
	Confidence Interval	(2-Sided) 95%; 12.0 to 27.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	104.7
	Confidence Interval	(2-Sided) 95%; 87.7 to 121.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; -9.8 to 24.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	43.6
	Confidence Interval	(2-Sided) 95%; 26.6 to 60.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	68.4
	Confidence Interval	(2-Sided) 95%; 51.3 to 85.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	54.3
	Confidence Interval	(2-Sided) 95%; 37.3 to 71.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	53.0
	Confidence Interval	(2-Sided) 95%; 36.0 to 70.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	292.5
	Confidence Interval	(2-Sided) 95%; 240.0 to 345.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2277
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.2
	Confidence Interval	(2-Sided) 95%; -20.3 to 84.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	173.1
	Confidence Interval	(2-Sided) 95%; 120.5 to 225.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	151.7
	Confidence Interval	(2-Sided) 95%; 99.1 to 204.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	129.8
	Confidence Interval	(2-Sided) 95%; 77.2 to 182.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	122.6
	Confidence Interval	(2-Sided) 95%; 70.0 to 175.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	295.3
	Confidence Interval	(2-Sided) 95%; 228.3 to 362.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0416
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	69.6
	Confidence Interval	(2-Sided) 95%; 2.7 to 136.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	204.4
	Confidence Interval	(2-Sided) 95%; 137.5 to 271.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	160.5
	Confidence Interval	(2-Sided) 95%; 93.5 to 227.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	133.0
	Confidence Interval	(2-Sided) 95%; 66.1 to 199.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	140.1
	Confidence Interval	(2-Sided) 95%; 73.1 to 207.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	219.5
	Confidence Interval	(2-Sided) 95%; 127.6 to 311.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	145.0
	Confidence Interval	(2-Sided) 95%; 53.2 to 236.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	200.2
	Confidence Interval	(2-Sided) 95%; 108.4 to 292.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	164.3
	Confidence Interval	(2-Sided) 95%; 72.4 to 256.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	146.6
	Confidence Interval	(2-Sided) 95%; 54.8 to 238.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0049
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	132.7
	Confidence Interval	(2-Sided) 95%; 40.8 to 224.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	209.3
	Confidence Interval	(2-Sided) 95%; 108.3 to 310.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	145.7
	Confidence Interval	(2-Sided) 95%; 44.7 to 246.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	200.7
	Confidence Interval	(2-Sided) 95%; 99.7 to 301.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0030
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	154.3
	Confidence Interval	(2-Sided) 95%; 53.3 to 255.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0046
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	146.8
	Confidence Interval	(2-Sided) 95%; 45.9 to 247.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0171
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	123.3
	Confidence Interval	(2-Sided) 95%; 22.3 to 224.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Good Drug Effects: Time to Maximum (Peak) Effect (TEmax)
Description	Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.258	1.017	1.017	0.517	1.017	1.017

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -3.7 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0105
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; 0.4 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7259
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7813
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5235
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.9 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8512
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Bad Drug Effects: Peak Effect (Emax)
Description	Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	5.8 (15.46)	16.4 (26.76)	26.5 (36.60)	20.6 (35.67)	16.9 (28.85)	31.4 (32.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0883
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; -1.7 to 23.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0241
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.8
	Confidence Interval	(2-Sided) 95%; 2.0 to 27.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0235
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.8
	Confidence Interval	(2-Sided) 95%; 2.0 to 27.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0901
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; -1.7 to 23.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1313
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.8
	Confidence Interval	(2-Sided) 95%; -3.0 to 22.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0982
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.8
	Confidence Interval	(2-Sided) 95%; -2.0 to 23.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	0.652 (3.5995)	0.977 (2.9225)	4.359 (12.9297)	0.445 (2.4294)	0.918 (2.4707)	3.621 (7.2682)
AUE (0-2)	1.270 (5.2494)	8.164 (18.3516)	16.023 (32.3331)	2.359 (8.9454)	4.840 (10.9280)	17.059 (28.6213)
AUE (0-8)	2.527 (7.6234)	28.984 (47.6235)	60.133 (104.8279)	22.195 (63.1674)	38.191 (83.7177)	81.777 (124.7723)
AUE (0-12)	2.527 (7.6234)	29.984 (48.2808)	71.195 (112.5641)	41.570 (88.3012)	46.691 (105.0132)	96.715 (157.0901)
AUE (0-24)	10.340 (44.8420)	30.203 (48.4810)	85.477 (145.5365)	138.039 (300.2416)	50.348 (111.5406)	102.434 (167.6105)
AUE (0-36)	19.715 (97.5206)	30.578 (48.6353)	85.852 (146.1250)	169.352 (379.2034)	51.473 (113.3471)	102.621 (167.6904)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0351
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; 0.2 to 6.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8751
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -3.3 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0795
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; -0.3 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8382
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -2.7 to 3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0289
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; 0.4 to 6.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7878
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -2.6 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.8
	Confidence Interval	(2-Sided) 95%; 5.6 to 24.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.821
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -8.1 to 10.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0094
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.3
	Confidence Interval	(2-Sided) 95%; 3.1 to 21.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4454
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -5.6 to 12.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0934
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.9
	Confidence Interval	(2-Sided) 95%; -1.3 to 17.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1358
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.0
	Confidence Interval	(2-Sided) 95%; -2.2 to 16.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	59.8
	Confidence Interval	(2-Sided) 95%; 27.0 to 92.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2365
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	19.7
	Confidence Interval	(2-Sided) 95%; -13.1 to 52.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0091
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	43.9
	Confidence Interval	(2-Sided) 95%; 11.1 to 76.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0335
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	35.7
	Confidence Interval	(2-Sided) 95%; 2.8 to 68.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0661
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	30.8
	Confidence Interval	(2-Sided) 95%; -2.1 to 63.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1074
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	26.9
	Confidence Interval	(2-Sided) 95%; -5.9 to 59.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0064
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	55.3
	Confidence Interval	(2-Sided) 95%; 15.8 to 94.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0543
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	38.8
	Confidence Interval	(2-Sided) 95%; -0.7 to 78.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0131
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	50.2
	Confidence Interval	(2-Sided) 95%; 10.7 to 89.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0297
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	43.9
	Confidence Interval	(2-Sided) 95%; 4.4 to 83.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0407
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	41.3
	Confidence Interval	(2-Sided) 95%; 1.8 to 80.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1710
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	27.5
	Confidence Interval	(2-Sided) 95%; -12.0 to 67.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3362
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-35.0
	Confidence Interval	(2-Sided) 95%; -106.7 to 36.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	126.9
	Confidence Interval	(2-Sided) 95%; 55.2 to 198.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1449
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	53.2
	Confidence Interval	(2-Sided) 95%; -18.5 to 124.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2882
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	38.7
	Confidence Interval	(2-Sided) 95%; -33.0 to 110.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1314
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	55.0
	Confidence Interval	(2-Sided) 95%; -16.6 to 126.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5808
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	20.1
	Confidence Interval	(2-Sided) 95%; -51.6 to 91.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1415
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-66.2
	Confidence Interval	(2-Sided) 95%; -154.6 to 22.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	149.1
	Confidence Interval	(2-Sided) 95%; 60.7 to 237.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2423
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	52.5
	Confidence Interval	(2-Sided) 95%; -35.9 to 140.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4980
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	30.4
	Confidence Interval	(2-Sided) 95%; -58.0 to 118.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2253
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	54.5
	Confidence Interval	(2-Sided) 95%; -33.9 to 142.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7945
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.7
	Confidence Interval	(2-Sided) 95%; -76.8 to 100.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax)
Description	Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.250	0.267	1.517	0.308	0.267	1.758

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0129
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -5.1 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.2
	Confidence Interval	(2-Sided) 95%; 2.0 to 6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5483
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -1.6 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5284
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -1.5 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1331
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; -0.5 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8732
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -2.1 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Feel Sick: Peak Effect (Emax)
Description	Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	3.1 (10.80)	5.4 (15.14)	8.8 (25.63)	10.1 (26.35)	2.6 (7.06)	11.7 (28.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4555
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; -5.9 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1495
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.9
	Confidence Interval	(2-Sided) 95%; -2.5 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0200
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.4
	Confidence Interval	(2-Sided) 95%; 1.8 to 20.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8668
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -10.3 to 8.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3904
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.1
	Confidence Interval	(2-Sided) 95%; -5.3 to 13.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6524
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -7.3 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	0.539 (3.0494)	0.629 (3.0605)	0.957 (3.3182)	0.035 (0.1463)	0.039 (0.1435)	0.996 (3.2217)
AUE (0-2)	0.727 (4.0198)	3.004 (14.4372)	4.160 (16.6354)	1.051 (4.5067)	0.758 (2.6560)	2.762 (6.8438)
AUE (0-8)	0.984 (4.2307)	5.176 (17.2686)	13.387 (40.8525)	12.324 (61.4559)	5.281 (17.1483)	15.449 (36.7603)
AUE (0-12)	0.984 (4.2307)	5.176 (17.2686)	13.387 (40.8525)	12.949 (63.8914)	6.156 (19.8004)	19.137 (42.3860)
AUE (0-24)	8.797 (44.3081)	5.645 (18.1099)	13.387 (40.8525)	64.699 (196.3450)	7.406 (22.7994)	19.605 (42.5054)
AUE (0-36)	18.359 (97.2004)	6.582 (19.7796)	13.387 (40.8525)	83.449 (267.7102)	7.594 (22.9559)	21.855 (43.9416)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1771
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -0.4 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3944
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.7 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1778
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; -0.4 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3960
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.7 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6125
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.9 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9059
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -1.1 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4585
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; -2.9 to 6.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8986
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -4.2 to 4.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3641
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -2.5 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9674
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -4.6 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5744
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -3.2 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3457
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -2.4 to 6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6664
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.7
	Confidence Interval	(2-Sided) 95%; -13.3 to 20.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1949
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; -5.8 to 28.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2009
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; -6.0 to 28.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6595
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.8
	Confidence Interval	(2-Sided) 95%; -13.1 to 20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3176
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.6
	Confidence Interval	(2-Sided) 95%; -8.3 to 25.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6423
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 95%; -12.9 to 20.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4358
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95%; -10.5 to 24.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1789
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.7
	Confidence Interval	(2-Sided) 95%; -5.4 to 28.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1131
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	14.0
	Confidence Interval	(2-Sided) 95%; -3.3 to 31.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5965
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -12.6 to 21.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3175
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.7
	Confidence Interval	(2-Sided) 95%; -8.5 to 25.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6551
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -13.3 to 21.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0354
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-45.3
	Confidence Interval	(2-Sided) 95%; -87.5 to -3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0100
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	55.2
	Confidence Interval	(2-Sided) 95%; 13.4 to 97.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5379
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	13.2
	Confidence Interval	(2-Sided) 95%; -29.0 to 55.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8768
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.3
	Confidence Interval	(2-Sided) 95%; -45.1 to 38.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7031
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.1
	Confidence Interval	(2-Sided) 95%; -33.8 to 49.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8507
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4
	Confidence Interval	(2-Sided) 95%; -45.8 to 37.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0381
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-62.3
	Confidence Interval	(2-Sided) 95%; -121.2 to -3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0318
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	64.0
	Confidence Interval	(2-Sided) 95%; 5.7 to 122.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6095
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.2
	Confidence Interval	(2-Sided) 95%; -43.6 to 74.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6470
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.6
	Confidence Interval	(2-Sided) 95%; -71.9 to 44.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8136
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.0
	Confidence Interval	(2-Sided) 95%; -51.4 to 65.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6699
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-12.6
	Confidence Interval	(2-Sided) 95%; -71.0 to 45.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Feel Sick: Time to Maximum (Peak) Effect (TEmax)
Description	Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.250	0.267	0.267	0.267	0.267	0.267

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1728
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -3.9 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2616
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7307
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -1.9 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5473
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.0 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4999
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -3.1 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5592
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.0 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Nausea: Peak Effect (Emax)
Description	Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	6.1 (18.90)	11.5 (25.07)	17.8 (32.11)	9.5 (26.18)	11.3 (23.47)	22.0 (33.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0217
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	13.3
	Confidence Interval	(2-Sided) 95%; 2.0 to 24.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5513
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -7.8 to 14.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0469
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.5
	Confidence Interval	(2-Sided) 95%; 0.2 to 22.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3604
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; -6.0 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2725
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.2
	Confidence Interval	(2-Sided) 95%; -5.0 to 17.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3461
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.4
	Confidence Interval	(2-Sided) 95%; -5.8 to 16.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	1.551 (8.7270)	1.313 (4.2183)	3.867 (13.3986)	0.043 (0.1510)	0.281 (1.0395)	2.797 (8.7018)
AUE (0-2)	3.309 (16.0847)	6.938 (18.5123)	11.500 (30.7880)	0.520 (2.3602)	3.813 (11.0316)	9.398 (19.9006)
AUE (0-8)	5.801 (21.1576)	17.656 (40.3906)	34.102 (88.7640)	12.465 (46.6764)	15.453 (33.4096)	39.648 (75.0136)
AUE (0-12)	5.801 (21.1576)	17.656 (40.3906)	40.602 (97.6330)	16.340 (58.2244)	18.828 (41.2148)	41.523 (78.2852)
AUE (0-24)	13.613 (54.7055)	17.656 (40.3906)	52.508 (132.8214)	76.402 (243.7336)	21.203 (45.1793)	42.992 (80.0147)
AUE (0-36)	22.988 (105.8442)	17.844 (40.3199)	52.508 (132.8214)	94.777 (325.6554)	21.391 (45.4013)	43.742 (79.9894)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1828
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3908
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -5.0 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2513
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -1.5 to 5.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5035
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -4.6 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1452
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -0.9 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9303
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -3.6 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0283
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.8
	Confidence Interval	(2-Sided) 95%; 0.9 to 16.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4861
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -10.5 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1809
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95%; -2.5 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8560
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -7.1 to 8.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2385
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.7
	Confidence Interval	(2-Sided) 95%; -3.1 to 12.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3479
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.7
	Confidence Interval	(2-Sided) 95%; -4.1 to 11.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0185
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	27.7
	Confidence Interval	(2-Sided) 95%; 4.7 to 50.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5471
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.9
	Confidence Interval	(2-Sided) 95%; -15.8 to 29.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0367
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	24.5
	Confidence Interval	(2-Sided) 95%; 1.5 to 47.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3797
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.1
	Confidence Interval	(2-Sided) 95%; -12.6 to 32.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1557
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	16.4
	Confidence Interval	(2-Sided) 95%; -6.3 to 39.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2904
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.2
	Confidence Interval	(2-Sided) 95%; -10.5 to 34.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0467
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	26.0
	Confidence Interval	(2-Sided) 95%; 0.4 to 51.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4056
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.7
	Confidence Interval	(2-Sided) 95%; -14.6 to 36.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0738
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	23.3
	Confidence Interval	(2-Sided) 95%; -2.3 to 48.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2987
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	13.4
	Confidence Interval	(2-Sided) 95%; -12.0 to 38.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0763
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.9
	Confidence Interval	(2-Sided) 95%; -2.4 to 48.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3396
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.3
	Confidence Interval	(2-Sided) 95%; -13.1 to 37.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2425
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-33.2
	Confidence Interval	(2-Sided) 95%; -89.1 to 22.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0281
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	62.1
	Confidence Interval	(2-Sided) 95%; 6.8 to 117.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4189
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.9
	Confidence Interval	(2-Sided) 95%; -33.0 to 78.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8310
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.0
	Confidence Interval	(2-Sided) 95%; -49.4 to 61.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2161
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	34.8
	Confidence Interval	(2-Sided) 95%; -20.6 to 90.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8905
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -51.5 to 59.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1597
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-51.8
	Confidence Interval	(2-Sided) 95%; -124.2 to 20.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0525
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	70.9
	Confidence Interval	(2-Sided) 95%; -0.8 to 142.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5294
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	23.1
	Confidence Interval	(2-Sided) 95%; -49.3 to 95.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9126
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -75.7 to 67.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3418
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	34.6
	Confidence Interval	(2-Sided) 95%; -37.1 to 106.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8833
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.3
	Confidence Interval	(2-Sided) 95%; -77.0 to 66.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Nausea: Time to Maximum (Peak) Effect (TEmax)
Description	Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.250	0.267	0.267	0.267	0.267	0.267

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0041
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.6
	Confidence Interval	(2-Sided) 95%; -6.1 to -1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.3
	Confidence Interval	(2-Sided) 95%; 1.9 to 6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8765
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -2.7 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4746
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -1.6 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4607
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -3.3 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2316
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -1.0 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Sleepy: Peak Effect (Emax)
Description	Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	24.7 (34.06)	56.8 (35.54)	72.0 (30.57)	38.3 (38.32)	59.2 (36.76)	76.1 (25.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	38.8
	Confidence Interval	(2-Sided) 95%; 26.4 to 51.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0136
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.8
	Confidence Interval	(2-Sided) 95%; 3.3 to 28.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0039
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	18.5
	Confidence Interval	(2-Sided) 95%; 6.1 to 31.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	36.1
	Confidence Interval	(2-Sided) 95%; 23.6 to 48.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0157
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.4
	Confidence Interval	(2-Sided) 95%; 2.9 to 27.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.9
	Confidence Interval	(2-Sided) 95%; 20.5 to 45.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	3.660 (11.1947)	9.160 (12.4734)	17.555 (18.6009)	9.004 (18.9625)	10.789 (17.0139)	22.590 (19.7659)
AUE (0-2)	17.809 (35.0786)	44.152 (38.4132)	66.906 (46.9339)	27.512 (43.9712)	49.125 (49.5132)	79.848 (46.1185)
AUE (0-8)	57.035 (117.1422)	196.691 (178.5590)	295.727 (204.5401)	127.855 (188.5158)	223.984 (196.8453)	378.309 (195.1978)
AUE (0-12)	68.785 (151.3384)	239.566 (244.9626)	352.289 (260.5164)	195.418 (271.9999)	270.109 (253.5547)	440.809 (232.3446)
AUE (0-24)	107.254 (299.1972)	295.941 (314.6515)	407.820 (342.4604)	346.949 (494.5935)	341.922 (407.7011)	487.559 (284.8306)
AUE (0-36)	135.941 (402.8944)	299.316 (316.1870)	414.008 (349.3465)	382.012 (585.0876)	362.922 (486.0190)	493.559 (290.1531)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 95%; 6.4 to 18.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2550
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; -2.6 to 9.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.4
	Confidence Interval	(2-Sided) 95%; 4.3 to 16.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0667
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.7
	Confidence Interval	(2-Sided) 95%; -0.4 to 11.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0075
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.3
	Confidence Interval	(2-Sided) 95%; 2.3 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1354
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -1.5 to 10.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	50.9
	Confidence Interval	(2-Sided) 95%; 34.2 to 67.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3905
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; -9.4 to 24.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	28.6
	Confidence Interval	(2-Sided) 95%; 11.9 to 45.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	29.6
	Confidence Interval	(2-Sided) 95%; 12.9 to 46.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0072
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.9
	Confidence Interval	(2-Sided) 95%; 6.3 to 39.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0035
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	25.0
	Confidence Interval	(2-Sided) 95%; 8.4 to 41.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	248.4
	Confidence Interval	(2-Sided) 95%; 188.6 to 308.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0263
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	68.2
	Confidence Interval	(2-Sided) 95%; 8.2 to 128.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	151.2
	Confidence Interval	(2-Sided) 95%; 91.3 to 211.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	165.4
	Confidence Interval	(2-Sided) 95%; 105.6 to 225.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	97.9
	Confidence Interval	(2-Sided) 95%; 38.3 to 157.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	138.4
	Confidence Interval	(2-Sided) 95%; 78.7 to 198.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	241.3
	Confidence Interval	(2-Sided) 95%; 162.8 to 319.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0028
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	121.1
	Confidence Interval	(2-Sided) 95%; 42.4 to 199.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	164.4
	Confidence Interval	(2-Sided) 95%; 85.8 to 243.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	198.0
	Confidence Interval	(2-Sided) 95%; 119.4 to 276.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0057
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	111.1
	Confidence Interval	(2-Sided) 95%; 32.8 to 189.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	168.1
	Confidence Interval	(2-Sided) 95%; 89.7 to 246.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0360
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	128.4
	Confidence Interval	(2-Sided) 95%; 8.5 to 248.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	221.5
	Confidence Interval	(2-Sided) 95%; 101.2 to 341.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0388
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	126.7
	Confidence Interval	(2-Sided) 95%; 6.6 to 246.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	223.2
	Confidence Interval	(2-Sided) 95%; 103.2 to 343.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0787
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	107.2
	Confidence Interval	(2-Sided) 95%; -12.4 to 226.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	181.3
	Confidence Interval	(2-Sided) 95%; 61.5 to 301.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1688
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	96.1
	Confidence Interval	(2-Sided) 95%; -41.2 to 233.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	220.3
	Confidence Interval	(2-Sided) 95%; 82.6 to 358.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1298
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	106.0
	Confidence Interval	(2-Sided) 95%; -31.5 to 243.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0029
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	210.4
	Confidence Interval	(2-Sided) 95%; 73.0 to 347.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1189
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	108.7
	Confidence Interval	(2-Sided) 95%; -28.3 to 245.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0284
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	153.6
	Confidence Interval	(2-Sided) 95%; 16.4 to 290.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Sleepy: Time to Maximum (Peak) Effect (TEmax)
Description	Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm)to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.758	2.025	2.508	2.000	2.017	2.033

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0327
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -3.4 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; 1.0 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7508
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.9 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1868
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -0.5 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9944
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2322
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.6 to 2.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Dizzy: Peak Effect (Emax)
Description	Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	3.6 (12.27)	23.4 (32.63)	30.6 (36.58)	12.0 (28.21)	19.5 (31.56)	39.3 (37.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	28.2
	Confidence Interval	(2-Sided) 95%; 16.8 to 39.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1421
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.4
	Confidence Interval	(2-Sided) 95%; -2.8 to 19.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	20.9
	Confidence Interval	(2-Sided) 95%; 9.5 to 32.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0064
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.8
	Confidence Interval	(2-Sided) 95%; 4.5 to 27.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1974
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.4
	Confidence Interval	(2-Sided) 95%; -3.9 to 18.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	19.5
	Confidence Interval	(2-Sided) 95%; 8.3 to 30.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	0.125 (0.5425)	7.117 (15.3098)	10.117 (15.9090)	1.238 (4.8747)	6.207 (12.4631)	14.043 (17.1328)
AUE (0-2)	0.922 (3.0851)	24.008 (41.3549)	28.758 (39.5123)	2.738 (10.8592)	18.402 (33.2777)	35.691 (44.1487)
AUE (0-8)	1.844 (6.2523)	47.297 (82.8121)	75.828 (117.4212)	23.934 (82.1109)	41.410 (79.0200)	117.738 (146.9677)
AUE (0-12)	1.906 (6.2536)	48.422 (85.1544)	83.266 (131.6787)	47.684 (145.0991)	42.160 (79.5674)	122.551 (150.8804)
AUE (0-24)	10.094 (49.8279)	49.922 (88.2865)	85.484 (136.4813)	120.934 (324.0852)	43.754 (81.6192)	122.895 (150.6660)
AUE (0-36)	19.844 (102.7158)	50.109 (88.1834)	85.859 (136.2835)	135.559 (386.0688)	44.129 (81.4783)	123.457 (150.3432)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	12.2
	Confidence Interval	(2-Sided) 95%; 7.1 to 17.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6868
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -4.1 to 6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0058
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 95%; 2.2 to 12.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0229
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95%; 0.8 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2168
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; -1.9 to 8.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0096
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	6.8
	Confidence Interval	(2-Sided) 95%; 1.7 to 11.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	33.0
	Confidence Interval	(2-Sided) 95%; 20.0 to 45.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8009
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -11.2 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0086
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	17.4
	Confidence Interval	(2-Sided) 95%; 4.5 to 30.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0089
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 95%; 4.4 to 30.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4224
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; -7.6 to 18.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	22.6
	Confidence Interval	(2-Sided) 95%; 9.8 to 35.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	96.1
	Confidence Interval	(2-Sided) 95%; 57.9 to 134.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2530
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	21.9
	Confidence Interval	(2-Sided) 95%; -15.8 to 59.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	78.6
	Confidence Interval	(2-Sided) 95%; 40.5 to 116.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0414
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	39.3
	Confidence Interval	(2-Sided) 95%; 1.6 to 77.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1329
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	28.9
	Confidence Interval	(2-Sided) 95%; -8.9 to 66.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0187
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	45.5
	Confidence Interval	(2-Sided) 95%; 7.7 to 83.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	76.9
	Confidence Interval	(2-Sided) 95%; 31.9 to 121.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0456
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	45.4
	Confidence Interval	(2-Sided) 95%; 0.9 to 89.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	82.8
	Confidence Interval	(2-Sided) 95%; 37.8 to 127.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0812
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	39.6
	Confidence Interval	(2-Sided) 95%; -5.0 to 84.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1174
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	35.5
	Confidence Interval	(2-Sided) 95%; -9.0 to 80.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0427
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	46.1
	Confidence Interval	(2-Sided) 95%; 1.5 to 90.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9318
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; -66.9 to 73.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	110.4
	Confidence Interval	(2-Sided) 95%; 41.2 to 179.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0226
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	81.5
	Confidence Interval	(2-Sided) 95%; 11.6 to 151.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3629
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	32.0
	Confidence Interval	(2-Sided) 95%; -37.3 to 101.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3077
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	35.9
	Confidence Interval	(2-Sided) 95%; -33.4 to 105.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2662
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	39.1
	Confidence Interval	(2-Sided) 95%; -30.1 to 108.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7875
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.4
	Confidence Interval	(2-Sided) 95%; -94.7 to 71.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0066
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	115.0
	Confidence Interval	(2-Sided) 95%; 32.6 to 197.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0540
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	81.7
	Confidence Interval	(2-Sided) 95%; -1.4 to 164.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6014
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	21.8
	Confidence Interval	(2-Sided) 95%; -60.6 to 104.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3885
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	36.1
	Confidence Interval	(2-Sided) 95%; -46.3 to 118.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4801
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	29.5
	Confidence Interval	(2-Sided) 95%; -52.9 to 112.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

33. Secondary Outcome

Title	Dizzy: Time to Maximum (Peak) Effect (TEmax)
Description	Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.250	0.758	0.767	0.258	0.292	0.758

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5494
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -2.5 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0626
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 95%; -0.1 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7216
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -1.6 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3647
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -1.0 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4456
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -2.7 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0500
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; 0.0 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	Pupillometry: Peak Effect (Emax)
Description	Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. Emax = Maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Mean (Standard Deviation) [mm]	-0.8 (0.38)	-2.0 (0.71)	-2.7 (0.72)	-2.4 (0.71)	-2.1 (0.63)	-3.0 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -0.69 to -0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.69
	Confidence Interval	(2-Sided) 95%; -1.86 to -1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -0.97 to -0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.40
	Confidence Interval	(2-Sided) 95%; -1.58 to -1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95%; -0.91 to -0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.29
	Confidence Interval	(2-Sided) 95%; -1.46 to -1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

35. Secondary Outcome

Title	Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x).
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	5.160 (0.7979)	4.022 (0.7658)	3.599 (0.6554)	5.039 (0.7893)	3.986 (0.6847)	3.489 (0.6738)
AUE (0-2)	10.164 (1.5890)	7.564 (1.3695)	6.226 (1.0741)	9.889 (1.6078)	7.384 (1.2278)	5.927 (1.0310)
AUE (0-8)	41.088 (6.4135)	30.129 (5.7346)	23.795 (4.0637)	33.605 (6.4972)	29.298 (5.4769)	21.913 (3.6297)
AUE (0-12)	62.550 (9.6352)	47.586 (9.5615)	38.713 (7.6202)	46.155 (8.8631)	46.136 (8.9456)	35.088 (6.4060)
AUE (0-24)	125.791 (19.2063)	103.711 (19.5429)	91.216 (17.4729)	83.530 (14.6930)	102.183 (17.7741)	83.832 (17.6410)
AUE (0-36)	188.828 (29.4183)	162.961 (29.2071)	149.454 (25.4599)	130.199 (23.0719)	161.977 (26.8529)	141.638 (28.1687)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.59
	Confidence Interval	(2-Sided) 95%; -1.75 to -1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3309
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -0.74 to -0.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 95%; -1.25 to -0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.59 to -0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 95%; -1.21 to -0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.03
	Confidence Interval	(2-Sided) 95%; -4.37 to -3.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2475
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.54 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.61
	Confidence Interval	(2-Sided) 95%; -1.96 to -1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.62
	Confidence Interval	(2-Sided) 95%; -2.96 to -2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.34
	Confidence Interval	(2-Sided) 95%; -1.68 to -1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-2): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.42
	Confidence Interval	(2-Sided) 95%; -2.76 to -2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.91
	Confidence Interval	(2-Sided) 95%; -13.21 to -10.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.23
	Confidence Interval	(2-Sided) 95%; -8.54 to -5.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-7.90
	Confidence Interval	(2-Sided) 95%; -9.20 to -6.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.24
	Confidence Interval	(2-Sided) 95%; -12.55 to -9.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.35
	Confidence Interval	(2-Sided) 95%; -7.65 to -5.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-10.36
	Confidence Interval	(2-Sided) 95%; -11.67 to -9.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.37
	Confidence Interval	(2-Sided) 95%; -13.16 to -9.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-16.07
	Confidence Interval	(2-Sided) 95%; -17.86 to -14.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.73
	Confidence Interval	(2-Sided) 95%; -13.53 to -9.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-15.71
	Confidence Interval	(2-Sided) 95%; -17.51 to -13.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-8.88
	Confidence Interval	(2-Sided) 95%; -10.67 to -7.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-14.19
	Confidence Interval	(2-Sided) 95%; -15.99 to -12.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8784
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -3.63 to 3.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-41.66
	Confidence Interval	(2-Sided) 95%; -45.02 to -38.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-19.63
	Confidence Interval	(2-Sided) 95%; -23.01 to -16.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-22.28
	Confidence Interval	(2-Sided) 95%; -25.67 to -18.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-12.50
	Confidence Interval	(2-Sided) 95%; -15.86 to -9.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-20.59
	Confidence Interval	(2-Sided) 95%; -23.98 to -17.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	10.64
	Confidence Interval	(2-Sided) 95%; 5.75 to 15.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-57.74
	Confidence Interval	(2-Sided) 95%; -62.63 to -52.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-22.18
	Confidence Interval	(2-Sided) 95%; -27.09 to -17.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-24.91
	Confidence Interval	(2-Sided) 95%; -29.83 to -20.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-13.53
	Confidence Interval	(2-Sided) 95%; -18.41 to -8.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-23.70
	Confidence Interval	(2-Sided) 95%; -28.62 to -18.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

36. Secondary Outcome

Title	Pupillometry: Time to Maximum (Peak) Effect (TEmax)
Description	Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. TEmax = Time to maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	2.275	1.517	1.517	12.050	1.775	1.533

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.73
	Confidence Interval	(2-Sided) 95%; -11.90 to -7.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.16
	Confidence Interval	(2-Sided) 95%; 2.99 to 7.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9766
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -2.13 to 2.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.61
	Confidence Interval	(2-Sided) 95%; -6.78 to -2.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7242
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -2.55 to 1.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-4.45
	Confidence Interval	(2-Sided) 95%; -6.62 to -2.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Other Pre-specified Outcome

Title	Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	50.020 (2.7443)	57.770 (11.2102)	64.820 (14.3058)	50.703 (3.2294)	61.125 (12.7119)	69.734 (12.6273)
AUE (0-8)	399.957 (8.2973)	431.973 (80.0157)	492.578 (112.1774)	404.578 (71.1457)	465.945 (110.9382)	531.586 (110.7145)
AUE (0-12)	600.645 (8.1980)	640.223 (111.0897)	704.328 (140.9602)	616.203 (130.7196)	677.320 (147.0075)	758.336 (160.5459)
AUE (0-24)	1202.863 (9.1566)	1267.410 (197.1640)	1337.016 (241.1654)	1203.828 (289.3240)	1285.289 (209.4193)	1398.836 (237.2094)
AUE (0-36)	1805.113 (11.7017)	1893.848 (298.9190)	1955.953 (326.5777)	1783.578 (361.8779)	1907.414 (310.0402)	2024.711 (347.2035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	19.0
	Confidence Interval	(2-Sided) 95%; 14.6 to 23.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8048
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -3.9 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	8.6
	Confidence Interval	(2-Sided) 95%; 4.2 to 13.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	11.0
	Confidence Interval	(2-Sided) 95%; 6.5 to 15.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.1
	Confidence Interval	(2-Sided) 95%; 2.7 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.6
	Confidence Interval	(2-Sided) 95%; 3.2 to 12.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	127.4
	Confidence Interval	(2-Sided) 95%; 93.6 to 161.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7837
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.7
	Confidence Interval	(2-Sided) 95%; -29.1 to 38.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	65.8
	Confidence Interval	(2-Sided) 95%; 32.0 to 99.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	66.3
	Confidence Interval	(2-Sided) 95%; 32.5 to 100.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	60.3
	Confidence Interval	(2-Sided) 95%; 26.5 to 94.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0640
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	31.9
	Confidence Interval	(2-Sided) 95%; -1.9 to 65.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	142.6
	Confidence Interval	(2-Sided) 95%; 94.5 to 190.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5169
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	15.8
	Confidence Interval	(2-Sided) 95%; -32.3 to 63.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	81.3
	Confidence Interval	(2-Sided) 95%; 33.2 to 129.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	77.1
	Confidence Interval	(2-Sided) 95%; 29.1 to 125.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0098
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	63.6
	Confidence Interval	(2-Sided) 95%; 15.6 to 111.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1078
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	39.4
	Confidence Interval	(2-Sided) 95%; -8.7 to 87.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	196.0
	Confidence Interval	(2-Sided) 95%; 116.9 to 275.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9726
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -77.7 to 80.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0050
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	114.1
	Confidence Interval	(2-Sided) 95%; 35.0 to 193.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0392
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	83.3
	Confidence Interval	(2-Sided) 95%; 4.2 to 162.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0883
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	68.7
	Confidence Interval	(2-Sided) 95%; -10.4 to 147.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1100
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	64.4
	Confidence Interval	(2-Sided) 95%; -14.7 to 143.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	242.9
	Confidence Interval	(2-Sided) 95%; 138.6 to 347.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6906
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-21.0
	Confidence Interval	(2-Sided) 95%; -125.3 to 83.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0259
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	118.7
	Confidence Interval	(2-Sided) 95%; 14.5 to 223.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0525
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	103.2
	Confidence Interval	(2-Sided) 95%; -1.1 to 207.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2558
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	60.2
	Confidence Interval	(2-Sided) 95%; -44.1 to 164.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0952
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	88.6
	Confidence Interval	(2-Sided) 95%; -15.7 to 192.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

38. Other Pre-specified Outcome

Title	Drug Liking: Time to Maximum (Peak) Effect (TEmax)
Description	Drug liking assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of "neither like nor dislike" (score of 50 mm), on the left with "strong disliking" (score of 0 mm) and on the right with "strong liking" (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.267	1.017	1.017	0.758	1.017	1.008

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0298
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -3.3 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 95%; 1.1 to 4.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6450
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -2.0 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0962
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -0.2 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1930
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -2.6 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0310
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; 0.2 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Other Pre-specified Outcome

Title	High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour, 0-12 Hour, 0-24 Hour and 0-36 Hour
Description	High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time 0 to x hours (0-x).
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
AUE (0-1)	0.785 (4.1738)	20.203 (22.8004)	40.801 (20.3235)	4.473 (11.7536)	27.465 (24.2206)	45.836 (20.4802)
AUE (0-8)	6.512 (16.7072)	119.055 (142.3080)	257.527 (163.9543)	39.145 (85.5494)	153.941 (150.3297)	322.250 (187.7896)
AUE (0-12)	6.512 (16.7072)	131.805 (168.5472)	277.715 (201.6860)	78.582 (166.6578)	160.004 (160.4458)	355.250 (237.6863)
AUE (0-24)	24.199 (69.6362)	131.930 (168.8668)	282.902 (215.7112)	161.613 (319.3473)	171.129 (180.2282)	362.531 (252.5074)
AUE (0-36)	34.137 (110.6283)	132.305 (170.0009)	282.902 (215.7112)	168.176 (337.3448)	173.379 (181.7041)	362.531 (252.5074)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	41.5
	Confidence Interval	(2-Sided) 95%; 33.9 to 49.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3763
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -4.2 to 10.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	18.3
	Confidence Interval	(2-Sided) 95%; 10.7 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	26.6
	Confidence Interval	(2-Sided) 95%; 19.1 to 34.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	20.7
	Confidence Interval	(2-Sided) 95%; 13.1 to 28.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-1): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	19.3
	Confidence Interval	(2-Sided) 95%; 11.8 to 26.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	284.3
	Confidence Interval	(2-Sided) 95%; 232.9 to 335.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2336
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	31.2
	Confidence Interval	(2-Sided) 95%; -20.4 to 82.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	167.3
	Confidence Interval	(2-Sided) 95%; 115.7 to 218.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	148.3
	Confidence Interval	(2-Sided) 95%; 96.8 to 199.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	135.6
	Confidence Interval	(2-Sided) 95%; 84.0 to 187.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-8): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	113.6
	Confidence Interval	(2-Sided) 95%; 62.1 to 165.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	278.3
	Confidence Interval	(2-Sided) 95%; 213.2 to 343.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0322
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	71.3
	Confidence Interval	(2-Sided) 95%; 6.1 to 136.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	195.4
	Confidence Interval	(2-Sided) 95%; 130.2 to 260.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	154.3
	Confidence Interval	(2-Sided) 95%; 89.2 to 219.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	143.2
	Confidence Interval	(2-Sided) 95%; 78.0 to 208.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-12): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	126.7
	Confidence Interval	(2-Sided) 95%; 61.7 to 191.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	202.4
	Confidence Interval	(2-Sided) 95%; 118.4 to 286.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	137.6
	Confidence Interval	(2-Sided) 95%; 53.3 to 221.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	192.9
	Confidence Interval	(2-Sided) 95%; 108.7 to 277.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	147.0
	Confidence Interval	(2-Sided) 95%; 63.0 to 231.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	148.1
	Confidence Interval	(2-Sided) 95%; 63.9 to 232.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-24): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0110
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	109.6
	Confidence Interval	(2-Sided) 95%; 25.5 to 193.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	196.0
	Confidence Interval	(2-Sided) 95%; 107.4 to 284.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	133.9
	Confidence Interval	(2-Sided) 95%; 45.0 to 222.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	190.9
	Confidence Interval	(2-Sided) 95%; 102.1 to 279.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	138.9
	Confidence Interval	(2-Sided) 95%; 50.3 to 227.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	147.8
	Confidence Interval	(2-Sided) 95%; 59.0 to 236.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	AUE (0-36): Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0273
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	100.0
	Confidence Interval	(2-Sided) 95%; 11.3 to 188.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Other Pre-specified Outcome

Title	High: Time to Maximum (Peak) Effect (TEmax)
Description	High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Completer analysis set included all randomized participants who completed all 6 periods of treatment phase and who contributed to post-dose PD data from each period.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	32	32	32	32	32	32
Median (Full Range) [hours]	0.250	1.017	1.017	0.767	1.017	1.017

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 Mg-I, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -5.0 to -1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 Mg-I
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; 1.3 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	ALO-02 60 mg- C, OXY 60 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8478
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 60 mg- C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6192
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.9 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	ALO-02 40 Mg-C, OXY 40 mg
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8857
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, ALO-02 40 Mg-C
	Comments	Mixed-effect model with treatment, period, and sequence as fixed effects, and participants nested within the sequence as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5092
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -2.1 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

41. Other Pre-specified Outcome

Title	Dose Normalized Maximum Observed Plasma Concentration (Cmax[dn]) of Oxycodone, Oxymorphone and Noroxycodone
Description	Cmax[dn]=Dose normalized maximum observed plasma concentration of participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the Pharmacokinetic (PK) parameters of interest. Here 'n' signifies those participants who were evaluable for specified category.

Arm/Group Title	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	36	37	38	37	36
Oxycodone (n= 36, 37, 38, 37, 36)	1.989 (0.62042)	1.672 (0.40716)	0.4978 (0.15863)	1.923 (0.54296)	1.514 (0.42099)
Oxymorphone (n= 36, 36, 38, 37, 35)	0.03271 (0.0155)	0.02847 (0.0149)	0.0068 (0.00365)	0.03182 (0.0161)	0.02419 (0.0118)
Noroxycodone (n= 36, 37, 38, 37, 36)	1.295 (0.37231)	1.123 (0.29543)	0.3672 (0.18111)	1.343 (0.36175)	1.026 (0.33231)

42. Other Pre-specified Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol
Description	Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest.

Arm/Group Title	ALO-02 40 Mg-C	ALO-02 60 Mg-I	ALO-02 60 Mg-C
Arm/Group Description	Single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed tablet (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.
Measure Participants	36	38	37
Naltrexone	1.389 (1.4633)	0.01808 (0.11145)	2.331 (2.4498)
6-beta-naltrexol	8.516 (2.4847)	0.3012 (1.8325)	13.70 (3.1369)

43. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone
Description	Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'n' signifies those participants who were evaluable for specified category.

Arm/Group Title	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	36	37	38	37	36
Oxycodone (n= 36, 37, 38, 37, 36)	1.03	1.03	12.1	0.583	1.04
Oxymorphone (n= 36, 36, 37, 37, 35)	0.559	0.567	14.0	0.567	0.550
Noroxycodone (n= 36, 37, 38, 37, 36)	1.03	1.07	14.1	0.600	1.05

44. Other Pre-specified Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol
Description	Participants who received ALO-02 were reported. 6-Beta-naltrexol is metabolites of naltrexone.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'n' signifies those participants who were evaluable for specified category.

Arm/Group Title	ALO-02 40 Mg-C	ALO-02 60 Mg-I	ALO-02 60 Mg-C
Arm/Group Description	Single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed tablet (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.
Measure Participants	36	38	37
Naltrexone (n= 36, 1, 37)	0.550	1.58	0.550
6-beta-naltrexol (n= 36, 19, 37)	0.567	1.55	0.550

45. Other Pre-specified Outcome

Title	Plasma Terminal Half-Life (t1/2) of Oxycodone
Description	Participants who received oxycodone and ALO-02 were reported. Oxymorphone and noroxycodone are metabolites of oxycodone.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies those participants evaluable for this measure.

Arm/Group Title	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	36	37	35	37	36
Median (Full Range) [hours]	4.470	4.240	9.340	4.300	4.195

46. Other Pre-specified Outcome

Title	Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour, 0-8 Hour 0-12 Hour and 0-24 Hour of Oxycodone
Description	AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Participants who received oxycodone were reported.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest.

Arm/Group Title	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	36	37	38	37	36
AUC (0-1)	45.21 (19.256)	37.60 (13.292)	0.02102 (0.05715)	72.25 (24.141)	53.38 (19.223)
AUC (0-2)	103.5 (29.463)	88.12 (20.159)	0.7834 (0.42296)	157.5 (37.317)	120.0 (34.767)
AUC (0-8)	276.8 (72.686)	265.0 (55.929)	79.08 (19.900)	405.5 (98.993)	366.5 (88.598)
AUC (0-12)	319.6 (87.905)	314.1 (72.753)	181.6 (43.706)	464.8 (121.19)	451.5 (116.62)
AUC (0-24)	356.2 (104.68)	355.9 (91.851)	455.3 (118.50)	513.9 (143.01)	527.8 (149.84)

47. Other Pre-specified Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone
Description	Area under the plasma concentration time-curve from zero to the last quantifiable concentration (AUClast). Participants who received oxycodone were reported.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest.

Arm/Group Title	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	36	37	38	37	36
Mean (Standard Deviation) [ng*hr/mL]	361.6 (108.39)	361.6 (95.617)	575.8 (150.15)	521.0 (147.32)	538.6 (155.71)

48. Other Pre-specified Outcome

Title	Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)dn] of Oxycodone
Description	[AUC (0 - ∞)dn]= Dose normalized area under the plasma concentration versus time curve [AUC(dn)] from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0- t) plus AUC (t - ∞). Participants who received oxycodone were reported. Participants who received oxycodone were reported.
Time Frame	pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose

Outcome Measure Data

Analysis Population Description

Parameter analysis set included all enrolled participants who received at least 1 dose of study drug and who had at least 1 of the PK parameters of interest. Here 'N' (number of participants analyzed) signifies those participants evaluable for this measure.

Arm/Group Title	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	36	37	35	37	36
Mean (Standard Deviation) [ng*hr/mL/mg]	9.079 (2.7120)	9.085 (2.3977)	10.88 (2.9327)	8.718 (2.4635)	9.018 (2.6095)

49. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 3 - 7 days following last study drug administration. Symptoms of withdrawal following naloxone administration (naloxone challenge phase) were not collected as adverse events unless they met the criteria for an SAE. AEs included SAEs as well as non-serious AEs which occurred during the trial.
Time Frame	Screening up to 28 days after last study drug administration (Day 29)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Naloxone	Oxycodone HCl 40 mg	Placebo Oxycodone HCl	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Naloxone HCl 0.2 mg intravenously followed by additional 0.6 mg naloxone HCl intravenously, each dose followed by an assessment for signs and symptoms of opioid withdrawal in naloxone challenge phase.	Single dose of oxycodone HCl 40 mg crushed tablet solution orally on either of 2 days in drug discrimination phase.	Single dose of placebo matched to oxycodone HCl crushed tablet solution orally on either of 2 days in drug discrimination phase.	Single dose of matching placebo orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	75	72	69	37	36	37	38	37	36
AEs	5 6.7%	70 NaN	14 NaN	12 NaN	29 NaN	37 NaN	27 NaN	34 NaN	36 NaN
SAEs	0 0%	1 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN

50. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change in Vital Sign Examinations
Description	Vital signs assessment included measurement of heart rate, systolic and diastolic blood pressures, respiratory rate and oral temperature. Criteria for clinically significant change in any vital sign examination was based on investigator's discretion.
Time Frame	Screening up to 7 days following last study drug administration (Day 8)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Naloxone	Oxycodone HCl 40 mg	Placebo Oxycodone HCl	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg
Arm/Group Description	Naloxone HCl 0.2 mg intravenously followed by additional 0.6 mg naloxone HCl intravenously, each dose followed by an assessment for signs and symptoms of opioid withdrawal in naloxone challenge phase.	Single dose of oxycodone HCl 40 mg crushed tablet solution orally on either of 2 days in drug discrimination phase.	Single dose of placebo matched to oxycodone HCl crushed tablet solution orally on either of 2 days in drug discrimination phase.	Single dose of matching placebo orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.
Measure Participants	75	72	69	37	36	37	38	37	36
Number [participants]	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN

51. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2)
Description	End-tidal carbon dioxide concentration in the expired air (EtCO2) was monitored using capnography in a sitting position. Criteria for clinically significant change in EtCO2 was based on investigator's discretion.
Time Frame	pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5 hours post-dose in drug discrimination phase; pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 14, 24, 36 hours post-dose in intervention period

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug. This outcome measure was not planned to be analyzed in "Naloxone Challenge Phase", as pre-specified in protocol.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg	Oxycodone HCl 40 mg	Placebo Oxycodone HCl
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg crushed tablet solution orally on either of 2 days in drug discrimination phase.	Single dose of placebo matched to oxycodone HCl crushed tablet solution orally on either of 2 days in drug discrimination phase.
Measure Participants	32	32	32	32	32	32	72	69
Number [participants]	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN

52. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2)
Description	Oxygen saturation of hemoglobin in blood (SpO2) was monitored using pulse oximetry continuously for 5 hours following dosing in the drug discrimination phase and continuously for 12 hours following dosing in the treatment phase, or longer at the discretion of the investigator. Individual measurements was collected in a sitting position. If SpO2 fall below 90 percent (%), the investigator might had administered oxygen via nasal cannula at a flow rate sufficient to maintain the SpO2 greater than or equal to 90%. Participants with fall in SpO2 below 90% were reported.
Time Frame	pre-dose up to 5 hours in drug discrimination phase; pre-dose up to 12 hours in intervention period

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug. This outcome measure was not planned to be analyzed in "Naloxone Challenge Phase", as pre-specified in protocol.

Arm/Group Title	Placebo	ALO-02 40 Mg-C	OXY 40 mg	ALO-02 60 Mg-I	ALO-02 60 mg- C	OXY 60 mg	Oxycodone HCl 40 mg	Placebo Oxycodone HCl
Arm/Group Description	Single dose of matching placebo solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 40 mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.	Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.	Single dose of oxycodone HCl 40 mg crushed tablet solution orally on either of 2 days in drug discrimination phase.	Single dose of placebo matched to oxycodone HCl crushed tablet solution orally on either of 2 days in drug discrimination phase.
Measure Participants	32	32	32	32	32	32	72	69
Number [participants]	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN

Adverse Events

Time Frame	Baseline up to 28 days after last study drug administration (Day 29)
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Naloxone		Oxycodone HCl 40 mg		Placebo		ALO-02 40 Mg-C		OXY 40 mg		ALO-02 60 Mg-I		ALO-02 60 Mg-C		OXY 60 mg		Placebo Oxycodone HCl
Arm/Group Description	Naloxone HCl 0.2 mg intravenously followed by additional 0.6 mg naloxone HCl intravenously, each dose followed by an assessment for signs and symptoms of opioid withdrawal in naloxone challenge phase.		Single dose of oxycodone HCl 40 mg crushed tablet solution orally on either of 2 days in drug discrimination phase.		Single dose of matching placebo solution orally in either of the first to sixth intervention periods.		Single dose of ALO-02 40mg/4.8 mg crushed tablet (ALO-02 40 mg-C) solution orally in either of the first to sixth intervention periods.		Single dose of oxycodone HCl 40 mg (OXY 40 mg) crushed tablet solution orally in either of the first to sixth intervention periods.		Single dose of ALO-02 60 mg/7.2 mg intact capsule (ALO-02 60 mg-I) solution orally in either of the first to sixth intervention periods.		Single dose of ALO-02 60 mg/7.2 mg crushed capsule (ALO-02 60 mg-C) solution orally in either of the first to sixth intervention periods.		Single dose of oxycodone HCl 60 mg (OXY 60 mg) crushed tablet solution orally in either of the first to sixth intervention periods.		Single dose of placebo matched to oxycodone HCl crushed tablet solution orally on either of 2 days in drug discrimination phase.
All Cause Mortality
	Naloxone		Oxycodone HCl 40 mg		Placebo		ALO-02 40 Mg-C		OXY 40 mg		ALO-02 60 Mg-I		ALO-02 60 Mg-C		OXY 60 mg		Placebo Oxycodone HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Naloxone		Oxycodone HCl 40 mg		Placebo		ALO-02 40 Mg-C		OXY 40 mg		ALO-02 60 Mg-I		ALO-02 60 Mg-C		OXY 60 mg		Placebo Oxycodone HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		1/72 (1.4%)		0/37 (0%)		0/36 (0%)		0/37 (0%)		0/38 (0%)		0/37 (0%)		0/36 (0%)		0/69 (0%)
Cardiac disorders
Sinus arrest	0/75 (0%)		1/72 (1.4%)		0/37 (0%)		0/36 (0%)		0/37 (0%)		0/38 (0%)		0/37 (0%)		0/36 (0%)		0/69 (0%)
Other (Not Including Serious) Adverse Events
	Naloxone		Oxycodone HCl 40 mg		Placebo		ALO-02 40 Mg-C		OXY 40 mg		ALO-02 60 Mg-I		ALO-02 60 Mg-C		OXY 60 mg		Placebo Oxycodone HCl
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/75 (1.3%)		70/72 (97.2%)		7/37 (18.9%)		28/36 (77.8%)		37/37 (100%)		26/38 (68.4%)		33/37 (89.2%)		36/36 (100%)		10/69 (14.5%)
Gastrointestinal disorders
Dry mouth	0/75 (0%)		14/72 (19.4%)		0/37 (0%)		0/36 (0%)		4/37 (10.8%)		1/38 (2.6%)		3/37 (8.1%)		5/36 (13.9%)		0/69 (0%)
Nausea	0/75 (0%)		13/72 (18.1%)		3/37 (8.1%)		4/36 (11.1%)		6/37 (16.2%)		5/38 (13.2%)		6/37 (16.2%)		7/36 (19.4%)		0/69 (0%)
Vomiting	0/75 (0%)		4/72 (5.6%)		0/37 (0%)		0/36 (0%)		2/37 (5.4%)		2/38 (5.3%)		1/37 (2.7%)		4/36 (11.1%)		0/69 (0%)
General disorders
Fatigue	0/75 (0%)		2/72 (2.8%)		1/37 (2.7%)		2/36 (5.6%)		5/37 (13.5%)		4/38 (10.5%)		4/37 (10.8%)		4/36 (11.1%)		3/69 (4.3%)
Feeling hot	0/75 (0%)		11/72 (15.3%)		1/37 (2.7%)		2/36 (5.6%)		5/37 (13.5%)		1/38 (2.6%)		7/37 (18.9%)		2/36 (5.6%)		1/69 (1.4%)
Feeling of relaxation	0/75 (0%)		3/72 (4.2%)		0/37 (0%)		1/36 (2.8%)		1/37 (2.7%)		0/38 (0%)		2/37 (5.4%)		1/36 (2.8%)		0/69 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/75 (0%)		0/72 (0%)		0/37 (0%)		0/36 (0%)		0/37 (0%)		0/38 (0%)		0/37 (0%)		2/36 (5.6%)		1/69 (1.4%)
Nervous system disorders
Dizziness	0/75 (0%)		10/72 (13.9%)		0/37 (0%)		6/36 (16.7%)		8/37 (21.6%)		7/38 (18.4%)		7/37 (18.9%)		10/36 (27.8%)		2/69 (2.9%)
Headache	0/75 (0%)		0/72 (0%)		2/37 (5.4%)		1/36 (2.8%)		4/37 (10.8%)		7/38 (18.4%)		5/37 (13.5%)		4/36 (11.1%)		0/69 (0%)
Somnolence	0/75 (0%)		21/72 (29.2%)		4/37 (10.8%)		14/36 (38.9%)		13/37 (35.1%)		10/38 (26.3%)		14/37 (37.8%)		17/36 (47.2%)		4/69 (5.8%)
Psychiatric disorders
Euphoric mood	0/75 (0%)		55/72 (76.4%)		1/37 (2.7%)		19/36 (52.8%)		31/37 (83.8%)		11/38 (28.9%)		23/37 (62.2%)		31/36 (86.1%)		1/69 (1.4%)
Hypervigilance	0/75 (0%)		1/72 (1.4%)		0/37 (0%)		0/36 (0%)		0/37 (0%)		0/38 (0%)		0/37 (0%)		2/36 (5.6%)		0/69 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/75 (0%)		5/72 (6.9%)		0/37 (0%)		0/36 (0%)		0/37 (0%)		1/38 (2.6%)		1/37 (2.7%)		3/36 (8.3%)		0/69 (0%)
Pruritus	0/75 (0%)		35/72 (48.6%)		0/37 (0%)		5/36 (13.9%)		18/37 (48.6%)		14/38 (36.8%)		8/37 (21.6%)		24/36 (66.7%)		1/69 (1.4%)
Pruritus generalised	1/75 (1.3%)		6/72 (8.3%)		0/37 (0%)		1/36 (2.8%)		4/37 (10.8%)		1/38 (2.6%)		0/37 (0%)		3/36 (8.3%)		0/69 (0%)
Vascular disorders
Hot flush	0/75 (0%)		0/72 (0%)		0/37 (0%)		0/36 (0%)		2/37 (5.4%)		0/38 (0%)		0/37 (0%)		0/36 (0%)		0/69 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.