Efficacy and Safety of Fentanyl Buccal Tablets Compared With Oxycodone for the Management of Break Through Pain

• Sponsor: Cephalon (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00463047
• Collaborator: (none)
• Enrollment: 323
• Locations: 45
• Arms: 2
• Duration (Months): 19.1
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Evaluate the efficacy of treatment with Fentanyl Buccal Tablets (FBT) compared with immediate release oxycodone in alleviating breakthrough pain in opioid tolerant patients with chronic pain.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain	Drug: Fentanyl Buccal Tablets Compared With Immediate-Release Oxycodone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 323 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Active-Controlled Crossover Study to Evaluate the Efficacy and Safety of Fentanyl Buccal Tablets Compared With Immediate-release Oxycodone for the Management of Breakthrough Pain in Opioid-Tolerant Patient With Chronic Pain
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fentanyl Buccal Tablets (FBT) This study includes a screening period, 2 open-label dose titration periods (in randomized order), and 2 double-blind treatment periods (in randomized order).	Drug: Fentanyl Buccal Tablets Compared With Immediate-Release Oxycodone; Patients will be randomly assigned in a 1:1 ratio either to titrate immediate-release oxycodone first and to titrate FBT second, or to titrate FBT first and immediate-release oxycodone second, followed by 2 double-blind crossover treatment periods (in randomized order). For the double-blind treatment period of the study involving FBT administration, a patient is randomly assigned to receive FBT at the 200, 400, 600, or 800 mcg strength found to be successful during open-label titration. For the double-blind treatment period of the study to which a patient is randomly assigned to receive immediate-release oxycodone, the patient will receive immediate-release oxycodone at the strength (15, 30, 45, or 60 mg) found to be successful during open-label titration.
Active Comparator: Oxycodone This study includes a screening period, 2 open-label dose titration periods (in randomized order), and 2 double-blind treatment periods (in randomized order).	Drug: Fentanyl Buccal Tablets Compared With Immediate-Release Oxycodone; Patients will be randomly assigned in a 1:1 ratio either to titrate immediate-release oxycodone first and to titrate FBT second, or to titrate FBT first and immediate-release oxycodone second, followed by 2 double-blind crossover treatment periods (in randomized order). For the double-blind treatment period of the study involving FBT administration, a patient is randomly assigned to receive FBT at the 200, 400, 600, or 800 mcg strength found to be successful during open-label titration. For the double-blind treatment period of the study to which a patient is randomly assigned to receive immediate-release oxycodone, the patient will receive immediate-release oxycodone at the strength (15, 30, 45, or 60 mg) found to be successful during open-label titration.

Outcome Measures

Primary Outcome Measures

1. Pain Intensity Difference (PID15) At 15 Minutes [Immediately pre-dose and fifteen minutes after administration of study drug]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

Secondary Outcome Measures

1. Pain Intensity Difference (PID 5) at 5 Minutes [Immediately before and 5 minutes after study drug administration]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID5 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 5 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

2. Pain Intensity Difference (PID 10) at 10 Minutes [Immediately before and 10 minutes after administration of study drug]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID10 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 10 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

3. Pain Intensity Difference (PID 30) at 30 Minutes [Immediately before and 10 minutes after study drug administration]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID30 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 30 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

4. Pain Intensity Difference (PID 45) at 45 Minutes [Immediately before and 45 minutes after study drug administration]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID45 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 45 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

5. Pain Intensity Difference (PID 60) at 60 Minutes [Immediately before and 60 minutes after administration of study drug]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID60 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 60 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

6. Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment [Immediately before and 5 minutes after administration of study drug]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID5 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 5 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 5 minutes divided by the baseline PI score times 100.

7. Percentage Change in Pain Intensity Difference (%PID) at 10 Minutes [Immediately before and 10 minutes after study drug administration]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID10 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 10 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 10 minutes divided by the baseline PI score times 100.

8. Percentage Change in Pain Intensity Difference (%PID) at 15 Minutes [Immediately before and 15 minutes after administration of study drug]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 15 minutes divided by the baseline PI score times 100.

9. Percentage Change in Pain Intensity Difference (%PID) at 30 Minutes [Immediately before and 30 minutes after study drug administration]

   Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID30 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 30 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 30 minutes divided by the baseline PI score times 100.

10. Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes [Immediately before and 45 minutes after study drug administration]

    Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID45 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 45 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 45 minutes divided by the baseline PI score times 100.

11. Percentage Change in Pain Intensity Difference (%PID) at 60 Minutes [Immediately before and 60 minutes after study drug administration]

    Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID60 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 60 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 60 minutes divided by the baseline PI score times 100.

12. Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30) [From 5 minutes after dosing through 30 minutes after dosing]

    PI scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. SPID30 were derived from PID values. The SPID30 scores during the double-blind treatment phase were calculated as the time- weighted sum of the PID scores from 5 through 30 minutes,after the administration of study drug. SPID30 = (⅓ x PID5) + (⅓ x PID10) + (⅓ x PID15) + PID30. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

13. Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60) [From 5 minutes after dosing through 60 minutes after dosing]

    PI scores were assessed on an 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine during the double-blind treatment period. The SPID60 was derived from PID values. The SPID60 scores during the double-blind treatment phase were calculated as the time- weighted sum of the PID scores from 5 through 60 minutes,after the administration of the study drug. SPID60 = SPID30 + PID45 + PID60. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

14. Pain Relief (PR) Score at 5 Minutes [Five minutes after administration of study drug]

    The PR score 5 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).

15. Pain Relief Score (PR) at 10 Minutes [10 minutes after treatment with study drug]

    The PR score 10 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).

16. Pain Relief Score (PR) at 15 Minutes [15 minutes after treatment with study drug]

    The PR score 15 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).

17. Pain Relief Score (PR) at 30 Minutes [30 minutes after treatment with study drug]

    The PR score 30 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).

18. Pain Relief Score (PR) at 45 Minutes [45 minutes after treatment with study drug]

    The PR score 45 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).

19. Pain Relief Score (PR) at 60 Minutes [60 minutes after treatment with study drug]

    The PR score 60 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).

20. Total Pain Relief (TOTPAR60) at 60 Minutes [From 5 minutes to 60 minutes after dosing]

    The mean TOTPAR at 60 minutes will be calculated for each episode as the weighted sum of Pain Relief (PR) scores (5-point Likert scale, 0 = none to 4 = complete) at each assessment of PR (during the double-blind treatment period) until 60 minutes after study drug administration, as follows: TOTPAR60 =(⅓ x PR5)+ (⅓ x PR10) +(⅓ x PR15)+ PR30 + PR45 + PR60. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.

21. Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR) [From 5 minutes through 60 minutes after study drug treatment]

    The PR score at set intervals after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete). The maximum TOTPAR score that could be achieved at 60 minutes is equal to 16; thus, %TOTPAR at 60 minutes is (TOTPAR60 /16) times 100.The % TOTPAR achieved 60 minutes after the administration of study drug was calculated during the double-blind treatment phase.

22. Time to Any Pain Relief (APR) by Treatment, <= 5 Minutes [From time was administered to 5 minutes after treatment]

    Time to APR was measured by stopwatch and by scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment period. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 5 minutes was compared.

23. Time to Any Pain Relief (APR) by Treatment, <=10 Minutes [From study drug treatment until 10 minutes after treatment]

    The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during the double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 10 minutes was compared.

24. Time to Any Pain Relief (APR) by Treatment, <=15 Minutes [From study drug administration to 15 minutes after treatment]

    The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 15 minutes was compared.

25. Time to Any Pain Relief (APR) by Treatment, <=30 Minutes [Time of study drug administration till 30 minutes after treatment]

    The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 30 minutes was compared.

26. Time to Any Pain Relief (APR) by Treatment, <=45 Minutes [Time of study drug treatment until 45 minutes after treatment]

    The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 45 minutes was compared.

27. Time to Any Pain Relief (APR) by Treatment, <=60 Minutes [Time of study drug treatment until 60 minutes after treatment]

    The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 60 minutes was compared.

28. Time to Meaningful Pain Relief (MPR) by Treatment, <= 5 Minutes [From time study drug was taken until 5 minutes after treatment]

    Time to MPR was measured by stopwatch and by scheduled questions at each time point up to 60 minutes after baseline during the double-blind treatment period. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to meaningful pain relief fell into that category was compared.

29. Time to Meaningful Pain Relief (MPR) by Treatment, <=10 Minutes [Time of study drug treatment until 10 minutes after treatment]

    The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 10 minutes was compared.

30. Time to Meaningful Pain Relief (MPR) by Treatment, <=15 Minutes [Time of study drug administration until 15 minutes after treatment]

    The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 15 minutes was compared.

31. Time to Meaningful Pain Relief (MPR) by Treatment, <=30 Minutes [Time of study drug administration until 30 minutes after treatment]

    The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 30 minutes was compared.

32. Time to Meaningful Pain Relief (MPR) by Treatment, <=45 Minutes [From study drug administration until 45 minutes after treatment]

    The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 45 minutes was compared.

33. Time to Meaningful Pain Relief (MPR) by Treatment, <=60 Minutes [Time of study drug administration until 60 minutes after treatment]

    The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 60 minutes was compared.

34. Standard Rescue Medication Usage [During the administration of study drug during the double blind treatment periods.]

    Any use of standard rescue medication after the administration of study drug for relief of Breakthrough Pain (BTP) during the double-blind treatment phase was recorded in the patient's diary. The number of breakthrough pain episodes for which study drug treatment was administered and which required rescue medication use was recorded.

35. Medication Performance Assessment 30 Minutes After-treatment [30 minutes post-treatment]

    The medication performance assessment assessed study drug performance on a 5-point categorical scale of 0-4 (0=poor, 1=fair,2=good, 3=very good, 4=excellent) 30 minutes after administration of study drug during the double-blind treatment periods and for the first 5 BTP episodes after each visit during the open-label extension period were recorded in the patient's paper diary. Patients were asked "How well did your study medication perform in controlling this breakthrough pain episode?" The number of episodes rated for each category were recorded.

36. Medication Performance Assessment 60 Minutes After-treatment [60 minutes post-treatment]

    The medication performance assessment assessed study drug performance on a 5-point categorical scale of 0-4 (0=poor, 1=fair,2=good, 3=very good, 4=excellent) 60 minutes after administration of study drug during the double-blind treatment periods and for the first 5 BTP episodes after each visit during the open-label extension period were recorded in the patient's paper diary. Patients were asked "How well did your study medication perform in controlling this breakthrough pain episode?" The number of episodes rated for each category were recorded.

37. Breakthrough Pain Preference Questionnaire [After completion of both double-blind treatment periods or early termination]

    The BTP preference questionnaire is a questionnaire used to measure patients' preference for FBT or immediate-release oxycodone for management of BTP. The question is used to determine a patient's preference between the study drugs given in the 2 double-blind treatment periods. The patient was asked to select 1 of the following: 1, a preference for study drug used in the 1st double-blind treatment period; 2, a preference for study drug used in the 2nd double-blind treatment period; or 3, no preference.

38. Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5) [The end of the first double-blind treatment period.]

    The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the end of the first double-blind treatment period (Visit 5) who responded to each option is presented.

39. Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6) [At the end of the second double-blind treatment period (Visit 6)]

    The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the end of the second double-blind treatment period (Visit 6) who responded to each option is presented.

40. Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at Endpoint (End of Second Double-blind Treatment Period or Last Observation After Start of Treatment Period) [Endpoint (End of second double-blind treatment period or last observation after start of treatment period)]

    The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the Endpoint (time of the last observation during the treatment period)who responded to each option is presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient has chronic pain of at least 3 months duration associated with: diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, complex regional pain syndrome, back pain, neck pain,fibromyalgia, chronic pancreatitis, osteoarthritis,or cancer.

• The patient is currently using 1 of the following: at least 60 mg of oral morphine/day, or at least 25 mcg of transdermal fentanyl/hour, or at least 30 mg of oxycodone/day, or at least 8 mg of hydromorphone/day, or an equianalgesic dose of another opioid/day as around-the-clock (ATC) therapy for at least 7 days before administration of the first dose of study drug

• The patient is willing to provide written informed consent to participate in this study.

• The patient is 18 through 80 years of age.

• Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing potential, using a medically accepted method of birth control and agree to continued use of this method for the duration of the study.

• Any patient with cancer should have a life expectancy of at least 3 months.

• The patient reports an average Pain Intensity (PI) score, over the prior 24 hours, of 6 or less (0=no pain through 10=pain as bad as you can imagine) for their chronic pain.

• The patient experiences, on average, 1 to 4 breakthrough pain (BTP) episodes per day while taking ATC opioid therapy, and on average, the duration of each BTP episode is less than 4 hours.

• The patient currently uses opioid therapy for alleviation of BTP episodes, occurring at the location of the chronic pain, and achieves at least partial relief.

• The patient must be willing and able to successfully self-administer the study drug,comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.

Exclusion Criteria:

• The patient has uncontrolled or rapidly escalating pain as determined by the investigator (i.e., the around-the-clock (ATC) therapy may be expected to change between the first and last treatments with study drug), or has pain uncontrolled by therapy that could adversely impact the safety of the patient or that could be compromised by treatment with study drug.

• The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse.

• The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in either study drug.

• The patient has cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with potent synthetic opioids.

• The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.

• The patient is expected to have surgery during the study that will impact the patient's chronic pain and/or BTP.

• The patient has had therapy before study drug treatment that, in the opinion of the investigator, could alter pain or response to pain medication.

• The patient is pregnant or lactating.

• The patient has participated in a previous study with FBT.

• The patient has participated in a study involving an investigational drug in the prior 30 days.

• The patient is currently using prescription FBT or immediate-release oxycodone for BTP and is unwilling to undergo re-titration.

• The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug.

• The patient has any other medical condition or is receiving concomitant medication/therapy (eg, regional nerve block) that could, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol,or compromise collected data.

• The patient is involved in active litigation in regard to the chronic pain currently being treated.

• The patient has a positive urine drug screen (UDS) for an illicit drug or a medication not prescribed for him/her or which is not medically explainable.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Clinical Therapeutics	Birmingham	Alabama	United States	35235
2	Birmingham Pain Center	Birmingham	Alabama	United States	35244
3	Arizona Research Center	Phoenix	Arizona	United States	85023
4	Desert Pain & Rehab Specialists/Redpoint Research	Phoenix	Arizona	United States	85029
5	Hope Research Institute	Phoenix	Arizona	United States	85050
6	Lovelace Scientific Resources, Inc.	Beverly Hills	California	United States	90211
7	City of Hope National Medical Center	Duarte	California	United States	91010
8	Samaritan Center for Medical Research, Med. Group	Los Gatos	California	United States	95032
9	Advanced Diagnostic Pain Treatment Center, PC	New Haven	Connecticut	United States	06511
10	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
11	Compass Research	Orlando	Florida	United States	32806
12	AvivoClin Clinical Services	Port Orange	Florida	United States	32127
13	Lovelace Scientific Resources, Inc.	Sarasota	Florida	United States	34233
14	Clinical Research of Tampa Bay, Inc.	Spring Hill	Florida	United States	34609
15	Stedman Clinical Trials, LLC	Tampa	Florida	United States	33613
16	Center for Prospective Outcome Studies, Inc.	Atlanta	Georgia	United States	30327
17	North Georgia Premier Research	Dawnsonville	Georgia	United States	30534
18	Taylor Research, LLC	Marietta	Georgia	United States	30060
19	DrugStudies America	Marietta	Georgia	United States	30066
20	Tristate Arthritis & Rheumatology Center, LLC	Evansville	Indiana	United States	47714
21	Rehabilitation Associates of Indiana	Indianapolis	Indiana	United States	46250
22	Integrated Clinical Trial Services, Inc.	West Des Moines	Iowa	United States	50265
23	International Clinical Research Institute, Inc.	Overland Park	Kansas	United States	66211
24	Kansas City Bone & Joint Clinic, Inc.	Overland Park	Kansas	United States	66211
25	Willis-Knighton Pain Management Center	Shreveport	Louisiana	United States	71103
26	The Rehabilitation Team West	Baltimore	Maryland	United States	21228
27	Mid Atlantic Pain Medicine Center	Pikesville	Maryland	United States	21208
28	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
29	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico	United States	87108
30	Metropolitan Hospital Center	New York	New York	United States	10029
31	Mount Sinai School of Medicine	New York	New York	United States	10029
32	Duke University Medical Center	Durham	North Carolina	United States	27710
33	PharmQuest	Greensboro	North Carolina	United States	27401
34	Peters Medical Research	High Point	North Carolina	United States	27262
35	Raleigh Neurology Associate	Raleigh	North Carolina	United States	27607
36	Columbus Clinical Research	Columbus	Ohio	United States	43213
37	Allegheny Pain Management	Altoona	Pennsylvania	United States	16602
38	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
39	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19146
40	Greenville Pharmaceutical	Greenville	South Carolina	United States	29615
41	Comprehensive Pain Specialists, PLLC	Hendersonville	Tennessee	United States	37075
42	Consultants in Pain Research	San Antonio	Texas	United States	78209
43	InVisions Consultants, LLC	San Antonio	Texas	United States	78218
44	Northwest Clinical Research Center	Bellevue	Washington	United States	98004
45	The Center for Pain Relief	Charleston	West Virginia	United States	25301

Sponsors and Collaborators

• Cephalon

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cephalon
• ClinicalTrials.gov Identifier: NCT00463047
• Other Study ID Numbers: C25608/3055/BP/MN
• First Posted: Apr 19, 2007
• Last Update Posted: May 28, 2012
• Last Verified: May 1, 2012

• Keywords provided by Cephalon: Breakthrough pain; Opioid-tolerant; Chronic pain
• Additional relevant MeSH terms: Chronic Pain; Breakthrough Pain; Fentanyl; Oxycodone

Study Results

Participant Flow

Recruitment Details	Subjects 18 to 80 years of age with chronic pain for at least 3 months, were opioid tolerant, on around-the-clock opioid therapy, with 1-4 breakthrough pain episodes a day were recruited from 46 centers in the United States. First participant screened: June 2007. Last participant last visit: February 2009.
Pre-assignment Detail	Prior to the double-blind treatment period, subjects participated in two titration periods to identify a "successful" and tolerated dose of Fentanyl Buccal Tablets (FBT) and immediate-release oxycodone. Subjects who did not titrate successfully were excluded from further participation in the study.

Arm/Group Title	FBT First Immediate Release Oxycodone Second	Immediate-Release Oxycodone First FBT Second
Arm/Group Description	Patients were randomized 1:1 to titrate Fentanyl Buccal Tablet (FBT) during the first titration period and then titrated immediate-release oxycodone during the second period or the reverse. Titration began with either 200 mcg FBT or 15 mg oxycodone taken as needed for breakthrough pain. If after 30 minutes pain relief was unsuccessful, a second dose could be taken. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased in 200 mcg increments for FBT and 15 mg increments for oxycodone. The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.	Patients were randomly assigned 1:1 to either titrate FBT during the first titration period and then titrated immediate-release oxycodone during the second period or the reverse. Titration began with either 200 mcg FBT or 15 mg oxycodone taken as needed for breakthrough pain. If after 30 minutes pain relief was unsuccessful, a second dose could be taken. If more than one dose was required for at least 1 of 3 breakthrough pain episodes in one day, the next day the dose was increased in 200 mcg increments for FBT and 15 mg increments for oxycodone. The maximum allowable dose was 800 mcg for FBT (4 tablets) and 60 mg (4 capsules) for oxycodone. If a dose was not tolerated the dose was lowered to the previous tolerated dose. Titration completed when successful analgesia was achieved with a tolerated dose or maximum dose was reached. If unsuccessful at maximum dose subject was discontinued from proceeding further in the study. Subjects who successfully titrated were randomized.
Period Title: Titration Period 1
STARTED	160	160
COMPLETED	123	121
NOT COMPLETED	37	39
Period Title: Titration Period 1
STARTED	123	121
COMPLETED	93	98
NOT COMPLETED	30	23
Period Title: Titration Period 1
STARTED	96	94
COMPLETED	93	90
NOT COMPLETED	3	4
Period Title: Titration Period 1
STARTED	93	90
COMPLETED	92	88
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Total Number of Patients
Arm/Group Description	Fentanyl Buccal Tablets (FBT) and Immediate-Release Oxycodone crossover. The total number of patients (323) reflect the number that were enrolled to participate in the study prior to the first titration period. Three subjects withdrew before receiving any study drug so they are not listed as being assigned to either dosing arm in the titration studies, leaving only 320 subjects who were evenly divided between the two groups.
Overall Participants	323
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	323 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.2 (9.81)
Sex: Female, Male (Count of Participants)
Female	188 58.2%
Male	135 41.8%
Region of Enrollment (participants) [Number]
United States	323 100%

Outcome Measures

1. Primary Outcome

Title	Pain Intensity Difference (PID15) At 15 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	Immediately pre-dose and fifteen minutes after administration of study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	0.82 (0.07)	0.59 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	The statistical hypothesis to be tested was:HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID15 for double-blind episodes for which patients use FBT and oxycodone (OXY), respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed effects ANOVA
	Comments	Crossover analysis
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.23
	Confidence Interval	() 95%; 0.18 to 0.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

2. Secondary Outcome

Title	Pain Intensity Difference (PID 5) at 5 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID5 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 5 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	Immediately before and 5 minutes after study drug administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure Episodes of breakthrough pain	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	0.08 (0.03)	0.05 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID5 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0081
	Comments	LS mean, SE of LS mean and p-value for treatment comparison are from ANOVA based on individual episodes with treatment as randomized, phase, and sequence as fixed factors and patient as random factor, using compound symmetry.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; 0.01 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

3. Secondary Outcome

Title	Pain Intensity Difference (PID 10) at 10 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID10 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 10 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	Immediately before and 10 minutes after administration of study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	0.30 (0.04)	0.22 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID10 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	LS mean, SE of LS mean and p-value for treatment comparison are from ANOVA based on individual episodes with treatment as randomized, phase, and sequence as fixed factors and patient as random factor, using compound symmetry.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; 0.05 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

4. Secondary Outcome

Title	Pain Intensity Difference (PID 30) at 30 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID30 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 30 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	Immediately before and 10 minutes after study drug administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	1.96 (0.09)	1.58 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID10 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	LS mean, SE of LS mean and p-value for treatment comparison are from ANOVA based on individual episodes with treatment as randomized, phase, and sequence as fixed factors and patient as random factor, using compound symmetry.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.37
	Confidence Interval	() 95%; 0.30 to 0.45
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

5. Secondary Outcome

Title	Pain Intensity Difference (PID 45) at 45 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID45 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 45 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	Immediately before and 45 minutes after study drug administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	2.87 (0.12)	2.59 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID45 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	LS mean, SE of LS mean and p-value for treatment comparison are from ANOVA based on individual episodes with treatment as randomized, phase, and sequence as fixed factors and patient as random factor, using compound symmetry.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; 0.20 to 0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

6. Secondary Outcome

Title	Pain Intensity Difference (PID 60) at 60 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID60 is the difference between the PI score from the episode baseline (immediately prior to study drug administration) and 60 minutes after the administration of the study drug. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	Immediately before and 60 minutes after administration of study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	3.35 (0.13)	3.19 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	The statistical hypothesis to be tested was: HO: µFBT = µOXY versus Ha: µFBT ≠ µoxy where µFBT and µOXY denote the mean PID60 for double-blind episodes for which patients use FBT and OXY, respectively. The primary variable was analyzed using a mixed effects ANOVA crossover model, with treatment as randomized (FBT or OXY), period, and treatment sequence (as randomized) as fixed factors and patient as a random factor, using compound symmetry for the variance-covariance matrix.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	LS mean, SE of LS mean and p-value for treatment comparison are from ANOVA based on individual episodes with treatment as randomized, phase, and sequence as fixed factors and patient as random factor, using compound symmetry.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

7. Secondary Outcome

Title	Percentage Change in Pain Intensity Difference (% PID) at 5 Minutes Post-treatment
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID5 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 5 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 5 minutes divided by the baseline PI score times 100.
Time Frame	Immediately before and 5 minutes after administration of study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Mean (Standard Error) [Percent change in units on a scale]	1.11 (0.45)	0.73 (0.37)

8. Secondary Outcome

Title	Percentage Change in Pain Intensity Difference (%PID) at 10 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID10 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 10 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 10 minutes divided by the baseline PI score times 100.
Time Frame	Immediately before and 10 minutes after study drug administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Mean (Standard Error) [Percentage change in units on a scale]	4.08 (0.76)	3.16 (0.57)

9. Secondary Outcome

Title	Percentage Change in Pain Intensity Difference (%PID) at 15 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID15 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 15 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 15 minutes divided by the baseline PI score times 100.
Time Frame	Immediately before and 15 minutes after administration of study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Mean (Standard Error) [Percent change in units on a scale]	11.40 (1.15)	8.59 (0.94)

10. Secondary Outcome

Title	Percentage Change in Pain Intensity Difference (%PID) at 30 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID30 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 30 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 30 minutes divided by the baseline PI score times 100.
Time Frame	Immediately before and 30 minutes after study drug administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Mean (Standard Error) [Percent change in units on a scale]	27.83 (1.50)	23.06 (1.33)

11. Secondary Outcome

Title	Percentage Change in Pain Intensity Difference (% PID) at 45 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID45 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 45 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 45 minutes divided by the baseline PI score times 100.
Time Frame	Immediately before and 45 minutes after study drug administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Mean (Standard Error) [Percent change in units on scale]	40.94 (1.76)	37.56 (1.57)

12. Secondary Outcome

Title	Percentage Change in Pain Intensity Difference (%PID) at 60 Minutes
Description	Pain intensity (PI) scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine after each episode of breakthrough pain during the double-blind treatment period. The PID60 is the difference between the PI scores from the episode baseline (immediately prior to study drug administration)and 60 minutes after the administration of the study drug. The difference is calculated and assessed as a percentage of the baseline pain intensity score. The percentage is calculated as the PID at 60 minutes divided by the baseline PI score times 100.
Time Frame	Immediately before and 60 minutes after study drug administration

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Mean (Standard Error) [Percent change in units on a scale]	48.08 (1.85)	46.16 (1.75)

13. Secondary Outcome

Title	Sum of Pain Intensity Difference at 30 Minutes Post-treatment (SPID30)
Description	PI scores were assessed on an 11-point numerical rating scale from 0 = no pain to 10 = pain as bad as you can imagine. SPID30 were derived from PID values. The SPID30 scores during the double-blind treatment phase were calculated as the time- weighted sum of the PID scores from 5 through 30 minutes,after the administration of study drug. SPID30 = (⅓ x PID5) + (⅓ x PID10) + (⅓ x PID15) + PID30. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	From 5 minutes after dosing through 30 minutes after dosing

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	2.36 (0.13)	1.87 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.49
	Confidence Interval	() 95%; 0.39 to 0.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

14. Secondary Outcome

Title	Sum of Pain Intensity Difference at 60 Minutes Post-treatment (SPID60)
Description	PI scores were assessed on an 11-point numerical rating scale from 0=no pain to 10=pain as bad as you can imagine during the double-blind treatment period. The SPID60 was derived from PID values. The SPID60 scores during the double-blind treatment phase were calculated as the time- weighted sum of the PID scores from 5 through 60 minutes,after the administration of the study drug. SPID60 = SPID30 + PID45 + PID60. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	From 5 minutes after dosing through 60 minutes after dosing

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PI scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Least Squares Mean (Standard Error) [Units on a scale]	8.58 (0.34)	7.65 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.34
	Estimation Comments

15. Secondary Outcome

Title	Pain Relief (PR) Score at 5 Minutes
Description	The PR score 5 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Time Frame	Five minutes after administration of study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Mean (Standard Deviation) [Units on a scale]	0.10 (0.43)	0.09 (0.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1966
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	P-value for the treatment comparison is from a one-sample Wilcoxon signed rank test.

16. Secondary Outcome

Title	Pain Relief Score (PR) at 10 Minutes
Description	The PR score 10 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Time Frame	10 minutes after treatment with study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Mean (Standard Deviation) [Units on a scale]	0.30 (0.57)	0.25 (0.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0275
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	P-value for the treatment comparison is from a one-sample Wilcoxon signed rank test.

17. Secondary Outcome

Title	Pain Relief Score (PR) at 15 Minutes
Description	The PR score 15 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Time Frame	15 minutes after treatment with study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Mean (Standard Deviation) [Units on a scale]	0.69 (0.74)	0.53 (0.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	P-value for the treatment comparison is from a one-sample Wilcoxon signed rank test.

18. Secondary Outcome

Title	Pain Relief Score (PR) at 30 Minutes
Description	The PR score 30 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Time Frame	30 minutes after treatment with study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Mean (Standard Deviation) [Units on a scale]	1.50 (0.83)	1.23 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	P-value for the treatment comparison is from a one-sample Wilcoxon signed rank test.

19. Secondary Outcome

Title	Pain Relief Score (PR) at 45 Minutes
Description	The PR score 45 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Time Frame	45 minutes after treatment with study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Mean (Standard Deviation) [Units on a scale]	2.08 (0.80)	1.89 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	P-value for the treatment comparison is from a one-sample Wilcoxon signed rank test.

20. Secondary Outcome

Title	Pain Relief Score (PR) at 60 Minutes
Description	The PR score 60 minutes after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete).
Time Frame	60 minutes after treatment with study drug

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Mean (Standard Deviation) [Units on a scale]	2.38 (0.76)	2.24 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0074
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	P-value for the treatment comparison is from a one-sample Wilcoxon signed rank test.

21. Secondary Outcome

Title	Total Pain Relief (TOTPAR60) at 60 Minutes
Description	The mean TOTPAR at 60 minutes will be calculated for each episode as the weighted sum of Pain Relief (PR) scores (5-point Likert scale, 0 = none to 4 = complete) at each assessment of PR (during the double-blind treatment period) until 60 minutes after study drug administration, as follows: TOTPAR60 =(⅓ x PR5)+ (⅓ x PR10) +(⅓ x PR15)+ PR30 + PR45 + PR60. Least squared mean was from an analysis of variance (ANOVA) with treatment as randomized, phase, and sequence as fixed factors and patient as a random factor using compound symmetry.
Time Frame	From 5 minutes to 60 minutes after dosing

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Measure breakthrough pain episodes	1676	1687
Least Squares Mean (Standard Error) [Units on a scale]	6.32 (0.16)	5.63 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	LS mean, SE of LS mean and p-value for treatment comparison are from ANOVA based on individual episodes with treatment as randomized, phase, and sequence as fixed factors and patient as random factor, using compound symmetry.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.69
	Confidence Interval	() 95%; 0.55 to 0.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

22. Secondary Outcome

Title	Percent Total Pain Relief at 60 Minutes Posttreatment (%TOTPAR)
Description	The PR score at set intervals after the administration of study drug during the double-blind treatment phase was recorded in the patient's diary. The PR scale is a 5-point categorical scale of 0-4 (0=none, 1=slight, 2=moderate, 3=a lot, 4=complete). The maximum TOTPAR score that could be achieved at 60 minutes is equal to 16; thus, %TOTPAR at 60 minutes is (TOTPAR60 /16) times 100.The % TOTPAR achieved 60 minutes after the administration of study drug was calculated during the double-blind treatment phase.
Time Frame	From 5 minutes through 60 minutes after study drug treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	178	178
Mean (Standard Deviation) [Percent change in units on a scale]	39.48 (15.67)	35.28 (14.27)

23. Secondary Outcome

Title	Time to Any Pain Relief (APR) by Treatment, <= 5 Minutes
Description	Time to APR was measured by stopwatch and by scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment period. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 5 minutes was compared.
Time Frame	From time was administered to 5 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	48	33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3022
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.5054
	Confidence Interval	(2-Sided) 95%; 0.7 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Time to Any Pain Relief (APR) by Treatment, <=10 Minutes
Description	The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during the double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 10 minutes was compared.
Time Frame	From study drug treatment until 10 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	286	215

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0268
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.4042
	Confidence Interval	(2-Sided) 95%; 1.0 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Time to Any Pain Relief (APR) by Treatment, <=15 Minutes
Description	The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APR fell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 15 minutes was compared.
Time Frame	From study drug administration to 15 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	687	540

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.4631
	Confidence Interval	(2-Sided) 95%; 1.2 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Time to Any Pain Relief (APR) by Treatment, <=30 Minutes
Description	The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 30 minutes was compared.
Time Frame	Time of study drug administration till 30 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	1259	1157

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0084
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.3184
	Confidence Interval	(2-Sided) 95%; 1.1 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Time to Any Pain Relief (APR) by Treatment, <=45 Minutes
Description	The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 45 minutes was compared.
Time Frame	Time of study drug treatment until 45 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	1499	1480

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5283
	Comments
	Method	Generalize estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.0788
	Confidence Interval	(2-Sided) 95%; 0.9 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Time to Any Pain Relief (APR) by Treatment, <=60 Minutes
Description	The time to APR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Any pain relief was defined as any subjective reduction in pain severity, even if not meaningful to patient. For each category (<5, <10, <15, <30, <45, <60 minutes, No APR-rescue medication used, and No APR-no rescue medication used)the number of episodes for which the time to APRfell into that category was compared. Here the number of episodes in which APR was achieved in less than or equal to 60 minutes was compared.
Time Frame	Time of study drug treatment until 60 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	1559	1565

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7110
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.9491
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Time to Meaningful Pain Relief (MPR) by Treatment, <= 5 Minutes
Description	Time to MPR was measured by stopwatch and by scheduled questions at each time point up to 60 minutes after baseline during the double-blind treatment period. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 minutes, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to meaningful pain relief fell into that category was compared.
Time Frame	From time study drug was taken until 5 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	9	18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3288
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.5355
	Confidence Interval	(2-Sided) 95%; 0.2 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Secondary Outcome

Title	Time to Meaningful Pain Relief (MPR) by Treatment, <=10 Minutes
Description	The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 10 minutes was compared.
Time Frame	Time of study drug treatment until 10 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	92	83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5145
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.1485
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Time to Meaningful Pain Relief (MPR) by Treatment, <=15 Minutes
Description	The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 15 minutes was compared.
Time Frame	Time of study drug administration until 15 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough episodes	1764	1758
Number [Number of episodes treated]	286	211

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0191
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.4481
	Confidence Interval	(2-Sided) 95%; 1.1 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

32. Secondary Outcome

Title	Time to Meaningful Pain Relief (MPR) by Treatment, <=30 Minutes
Description	The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 30 minutes was compared.
Time Frame	Time of study drug administration until 30 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	787	636

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.4396
	Confidence Interval	(2-Sided) 95%; 1.2 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

33. Secondary Outcome

Title	Time to Meaningful Pain Relief (MPR) by Treatment, <=45 Minutes
Description	The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 45 minutes was compared.
Time Frame	From study drug administration until 45 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	1179	1060

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0044
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.3426
	Confidence Interval	(2-Sided) 95%; 1.1 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	Time to Meaningful Pain Relief (MPR) by Treatment, <=60 Minutes
Description	The time to MPR was measured by stopwatch and scheduled questions at each time point up to 60 minutes after baseline during double-blind treatment periods. Meaningful pain relief was defined as a subject reduction of pain intensity that the subject found to be meaningful (substantive). For each category (<5, <10, <15, <30, <45, <60 min, No MPR-rescue medication used, and No MPR-no rescue medication used)the number of episodes for which the time to MPR fell into that category was compared. Here the number of episodes in which MPR was achieved in less than or equal to 60 minutes was compared.
Time Frame	Time of study drug administration until 60 minutes after treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined by at least one episode of breakthrough pain treated with FBT and at least one with oxycodone. No imputation was done if subject never answered APR/MPR question. If responded only as no, remaining missing imputed as no. If at least 1 yes, remaining missing imputed as yes.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	1359	1313

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2184
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.1448
	Confidence Interval	(2-Sided) 95%; 0.9 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

35. Secondary Outcome

Title	Standard Rescue Medication Usage
Description	Any use of standard rescue medication after the administration of study drug for relief of Breakthrough Pain (BTP) during the double-blind treatment phase was recorded in the patient's diary. The number of breakthrough pain episodes for which study drug treatment was administered and which required rescue medication use was recorded.
Time Frame	During the administration of study drug during the double blind treatment periods.

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Number [Number of episodes treated]	144	131

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A logit link function and compound symmetry working correlation were applied in this model.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5808
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.9249
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

36. Secondary Outcome

Title	Medication Performance Assessment 30 Minutes After-treatment
Description	The medication performance assessment assessed study drug performance on a 5-point categorical scale of 0-4 (0=poor, 1=fair,2=good, 3=very good, 4=excellent) 30 minutes after administration of study drug during the double-blind treatment periods and for the first 5 BTP episodes after each visit during the open-label extension period were recorded in the patient's paper diary. Patients were asked "How well did your study medication perform in controlling this breakthrough pain episode?" The number of episodes rated for each category were recorded.
Time Frame	30 minutes post-treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Excellent	45	18
Very good	153	104
Good	533	343
Fair	450	566
Poor	334	489
No response	249	238

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A cumulative logit link function and independent working correlation were applied in this model. Treatment differences for each time point were measured across all categories of responses.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.8908
	Confidence Interval	(2-Sided) 95%; 1.7 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Secondary Outcome

Title	Medication Performance Assessment 60 Minutes After-treatment
Description	The medication performance assessment assessed study drug performance on a 5-point categorical scale of 0-4 (0=poor, 1=fair,2=good, 3=very good, 4=excellent) 60 minutes after administration of study drug during the double-blind treatment periods and for the first 5 BTP episodes after each visit during the open-label extension period were recorded in the patient's paper diary. Patients were asked "How well did your study medication perform in controlling this breakthrough pain episode?" The number of episodes rated for each category were recorded.
Time Frame	60 minutes post-treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set defined as having at least one evaluable episode of breakthrough pain treated with FBT and at least one with oxycodone. An episode was evaluable if it had a valid pain intensity measurement immediately prior to drug administration. No imputation for missing breakthrough pain episodes, but LOCF was applied for missing PR scores.

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Measure breakthrough pain episodes	1764	1758
Excellent	158	101
Very good	562	424
Good	679	726
Fair	210	335
Poor	128	146
No response	27	26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl Buccal Tablets (FBT), Immediate-Release Oxycodone
	Comments	Analysis is based on a generalized estimating equation model with treatment as a fixed effect and patient as a random effect. A cumulative logit link function and independent working correlation were applied in this model. Treatment differences for each time point were measured across all categories of responses.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Generalized estimating equation
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.5841
	Confidence Interval	(2-Sided) 95%; 1.4 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

38. Secondary Outcome

Title	Breakthrough Pain Preference Questionnaire
Description	The BTP preference questionnaire is a questionnaire used to measure patients' preference for FBT or immediate-release oxycodone for management of BTP. The question is used to determine a patient's preference between the study drugs given in the 2 double-blind treatment periods. The patient was asked to select 1 of the following: 1, a preference for study drug used in the 1st double-blind treatment period; 2, a preference for study drug used in the 2nd double-blind treatment period; or 3, no preference.
Time Frame	After completion of both double-blind treatment periods or early termination

Outcome Measure Data

Analysis Population Description

Double-blind safety analysis set: 190 subjects who received both study drugs in this crossover study completed the Breakthrough Pain Preference Questionnaire after completing treatment

Arm/Group Title	Total
Arm/Group Description	Includes all patients who participated in the double-blind treatment period and completed treatment.
Measure Participants	190
Preferred Fentanyl Buccal Tablet (FBT)	99 30.7%
Preferred Immediate-Release Oxycodone	63 19.5%
No preference	15 4.6%
Missing	13 4%

39. Secondary Outcome

Title	Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the First Double-blind Treatment Period (Visit 5)
Description	The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the end of the first double-blind treatment period (Visit 5) who responded to each option is presented.
Time Frame	The end of the first double-blind treatment period.

Outcome Measure Data

Analysis Population Description

Double-blind safety analysis set: 88 subjects who received FBT and 90 subjects who received Oxycodone in the first double-blind period

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	88	90
Prior Medication	15 4.6%	22 NaN
Study Medication	61 18.9%	50 NaN
No Preference	12 3.7%	18 NaN

40. Secondary Outcome

Title	Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at the End of the Second Double-blind Treatment Period (Visit 6)
Description	The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the end of the second double-blind treatment period (Visit 6) who responded to each option is presented.
Time Frame	At the end of the second double-blind treatment period (Visit 6)

Outcome Measure Data

Analysis Population Description

Double-blind safety analysis set: 83 subjects who received FBT and 87 subjects who received Oxycodone in the second double-blind period

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	83	87
Prior Medication	10 3.1%	19 NaN
Study Medication	63 19.5%	59 NaN
No Preference	10 3.1%	9 NaN

41. Secondary Outcome

Title	Pain Flare Treatment Satisfaction (PFTS) Questionnaire - Question 21 at Endpoint (End of Second Double-blind Treatment Period or Last Observation After Start of Treatment Period)
Description	The PFTS is used to measure patient's satisfaction with study drug. Although the full scale has 25 questions, the question that is most useful (and least redundant with prior scales) for assessing the efficacy of the study drug is Question 21 which states: Which medication would you prefer to use when treating your pain flares? The subject can choose either: Prior medication, Study medication, or No preference. The number of subjects in each treatment group at the Endpoint (time of the last observation during the treatment period)who responded to each option is presented.
Time Frame	Endpoint (End of second double-blind treatment period or last observation after start of treatment period)

Outcome Measure Data

Analysis Population Description

Double-blind safety analysis set: 88 subjects who received FBT and 94 subjects who received Oxycodone at any time during the double-blind treatment period who completed the PFTS questionnaire

Arm/Group Title	Fentanyl Buccal Tablets (FBT)	Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients.	Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug.
Measure Participants	183	183
Prior Medication	11 3.4%	19 NaN
Study Medication	66 20.4%	63 NaN
No Preference	12 3.7%	12 NaN

Adverse Events

Time Frame	Adverse events were monitored throughout the two titration periods and double-blind treatment periods. Each titration period was 7-10 days in length and each double-blind treatment period was 7-17 days. The average duration of treatment was 24.2 days.
Adverse Event Reporting Description	323 subjects were enrolled, 3 discontinued before receiving any study drug. 320 were randomized to titrate either FBT or oxycodone in first titration period. 36 received only FBT and discontinued (leaving 284 who received oxycodone), 39 received only oxycodone and discontinued leaving 281 who received FBT).
Arm/Group Title	Fentanyl Buccal Tablets (FBT)		Immediate-Release Oxycodone
Arm/Group Description	FBT or matching placebo during the 2 double-blind treatment periods at doses of 200, 400, 600, and 800 mcg was self-administered by patients. This group includes all subjects in this study who had taken at least one dose of FBT in the course of the study, including both titration periods and both double-blind treatment periods. 320 subjects were randomized to titrate either FBT or oxycodone. 39 subjects received only oxycodone before discontinuing leaving 281 who received FBT during the study. 36 subjects received only FBT before discontinuing, leaving only 284 who received oxycodone.		Immediate-release oxycodone (or matching placebo) at doses of 15,30, 45, and 60 mg was self administered. The double-blind, treatment period used a 2 period crossover design in which the patient first managed 10 episodes with 1 of the 2 blinded study drugs (successful doses of immediate-release oxycodone or FBT) and then managed a subsequent 10 episodes with the other blinded study drug. This arm represents all subjects who had exposure to at least one dose of immediate-release oxycodone either during the titration periods or double-blind periods. 320 subjects were randomized to titrate either FBT or oxycodone. 39 subjects received only oxycodone before discontinuing leaving 281 who received FBT during the study. 36 subjects received only FBT before discontinuing, leaving only 284 who received oxycodone.
All Cause Mortality
	Fentanyl Buccal Tablets (FBT)		Immediate-Release Oxycodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fentanyl Buccal Tablets (FBT)		Immediate-Release Oxycodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/281 (0.4%)		0/284 (0%)
Infections and infestations
Pneumonia	1/281 (0.4%)	2	0/284 (0%)	0
Other (Not Including Serious) Adverse Events
	Fentanyl Buccal Tablets (FBT)		Immediate-Release Oxycodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/281 (28.1%)		49/284 (17.3%)
Gastrointestinal disorders
Nausea	26/281 (9.3%)		11/284 (3.9%)
Diarrhea	6/281 (2.1%)		3/284 (1.1%)
Vomiting	4/281 (1.4%)		3/284 (1.1%)
Constipation	1/281 (0.4%)		4/284 (1.4%)
Dry mouth	1/281 (0.4%)		3/284 (1.1%)
Stomach discomfort	3/281 (1.1%)		0/284 (0%)
General disorders
Application site pain	13/281 (4.6%)		0/284 (0%)
Application site ulcer	11/281 (3.9%)		0/284 (0%)
Fatigue	2/281 (0.7%)		4/284 (1.4%)
Application site erythema	5/281 (1.8%)		0/284 (0%)
Application site irritation	8/281 (2.8%)		0/284 (0%)
Infections and infestations
Nasopharyngitis	4/281 (1.4%)		3/284 (1.1%)
Injury, poisoning and procedural complications
Fall	2/281 (0.7%)		3/284 (1.1%)
Nervous system disorders
Headache	12/281 (4.3%)		8/284 (2.8%)
Dizziness	9/281 (3.2%)		2/284 (0.7%)
Somnolence	6/281 (2.1%)		5/284 (1.8%)
Sedation	3/281 (1.1%)		2/284 (0.7%)
Psychiatric disorders
Euphoric mood	1/281 (0.4%)		3/284 (1.1%)
Skin and subcutaneous tissue disorders
Pruritus	2/281 (0.7%)		7/284 (2.5%)
Hyperhidrosis	3/281 (1.1%)		1/284 (0.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.