A Study of the Effectiveness and Safety of Sustained-release Hydromorphone (a Strong Opioid) in Patients With Chronic Noncancer Pain.

• Sponsor: Janssen Pharmaceutica N.V., Belgium (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00261495
• Collaborator: (none)
• Enrollment: 504
• Locations: 54
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness and safety of sustained- release hydromorphone, formulated to release slowly over time, taken once daily, and controlled- release oxycodone taken twice daily, in patients with chronic non-cancer pain. The study will also determine the dose of sustained-release hydromorphone that provides a level of pain control that is equal to the pain control provided by control-released oxycodone (equi-analgesic dosage).

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: OROS hydromorphone HCl; Drug: Oxycodone	Phase 3

Detailed Description

Conventional immediate-release forms of hydromorphone and oxycodone have a relatively short duration of action that require dosing every 4 to 6 hours. To counterbalance the drawback of repeated opioid intake, sustained-release formulations of oxycodone and hydromorphone were developed that allow twice-daily dosing. Subsequently, a novel, once-daily, extended-release hydromorphone formulation was developed to further enhance ease of treatment and improve effectiveness in the treatment of severe pain. This is a randomized, open-label, comparative, parallel-group, 24-week flexible-dose study in patients with chronic noncancer pain severe enough to require continuous opioid therapy. Patients will receive either 8 mg of sustained-release hydromorphone, taken once daily or 10 mg of controlled-release oxycodone, taken twice daily. Individual adjustments in dosing will be performed to achieve satisfactory pain control, up to a maximum daily dosage of 32 mg for hydromorphone and 80 mg for oxycodone. The primary efficacy outcome will be the determination of the dose of hydromorphone that produces a level of pain control that is equal to the pain control provided by oxycodone (equi-analgesic dose). Safety will be monitored throughout the study. The study hypothesis is that sustained-release hydromorphone taken once daily is well tolerated and is not inferior with regard to pain control to controlled-release oxycodone taken twice daily.

Amendment:

Amendment was made to the duration of the study from duration of '24 weeks' to '52 weeks' in order to collect long-term safety and efficacy data. OROS hydromorphone 8, 16, or 32 mg tablets QD or SR oxycodone 10, 20, or 40 mg tablets BID. Individual adjustments in dosing performed to achieve satisfactory pain control over 24 weeks. Amendment: treatment duration was extended to 52 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 504 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Open-Label, Comparative Parallel Group Study to Assess Efficacy and Safety on Flexible Dosages of OROS Hydromorphone Once-Daily Compared to Sustained Release Oxycodone Twice Daily in Subjects With Chronic Non-malignant Pain Requiring Continuous Opioid Therapy.
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oxycodone	Drug: Oxycodone; 10, 20, or 40 mg twice a day for 52 weeks (flexible dosing)
Experimental: OROS hydromorphone HCl	Drug: OROS hydromorphone HCl; 8 to 32 mg once daily for 52 weeks (flexible dosing)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Brief Pain Inventory (BPI) Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Per Protocol [PP] Population) [baseline and week 24]

   Assessment of non-inferiority of OROS hydromorphone compared with sustained release (SR) oxycodone with regard to pain control by measuring the change from baseline in pain severity, using BPI item 6 "pain right now" score at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain right now".

2. Change From Baseline in BPI Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Intent to Treat [ITT] Population) [baseline and week 24]

   Assessment of non-inferiority of OROS hydromorphone compared with SR oxycodone with regard to pain control by measuring the change from baseline in pain severity, using BPI item 6 "pain right now" score at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain right now".

3. Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (PP Population) [week 24]

   If non-inferiority of OROS hydromorphone was established, the daily dose of OROS hydromorphone and SR oxycodone that induced the same pain control was to be calculated (average dose used at week 24). Relative equi-analgesic dose was defined as mean dose/allowed maximum dose*100. Allowed maximum doses were 32mg OROS hydromorphone and 80mg SR oxycodone respectively.

4. Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (ITT Population) [week 24]

   If non-inferiority of OROS hydromorphone was established, the daily dose of OROS hydromorphone and SR oxycodone that induced the same pain control was to be calculated (average dose used at week 24). Relative equi-analgesic dose was defined as mean dose/allowed maximum dose*100. Allowed maximum doses were 32mg OROS hydromorphone and 80mg SR oxycodone respectively.

5. Equi-analgesic Dose at Steady-state (PP Population) [week 4 to week 24]

   Dose of OROS hydromorphone and SR oxycodone that induced the same pain control at steady state, defined as the mean dose from week 4 to week 24.

6. Equi-analgesic Dose at Steady State (ITT Population) [week 4 to week 24]

   Dose of OROS hydromorphone and SR oxycodone that induced the same pain control at steady state, defined as the mean dose from week 4 to week 24.

Secondary Outcome Measures

1. Change From Baseline in BPI Pain Severity Sub-score "Pain at Its Worst" (BPI Item 3) at Week 24 (ITT Population) [baseline and week 24]

   Change from baseline to week 24 in BPI pain severity, pain at its worst (BPI item 3) assessed using the BPI questionnaire. Score values ranges from 0 (no pain) to 10 (pain as bad as you can imagine). Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its worst".

2. Change From Baseline in Sleep Quality at Week 24 [baseline and week 24]

   Change from baseline in sleep quality was assessed using the Medical Outcomes Study (MOS) questionnaire at week 24, specifically the sleep subscale index I. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improved sleep quality.

3. Change From Baseline in Subject Diary Evening Mean Pain Score "Pain Right Now" at Week 24 [baseline and week 24]

   Change from baseline to week 24 in subject diary evening mean pain score "pain right now". Subjects rated the severity of "pain right now" on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary evening mean pain score "pain right now".

4. Change From Baseline in Subject Diary Morning Mean Pain Score "Pain Right Now" at Week 24 [baseline and week 24]

   Change from baseline to week 24 in subject diary morning mean pain score "pain right now". Subjects rated the severity of "pain right now" on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary evening mean pain score "pain right now".

5. Number of Subjects With Dose Escalation [week 4 and week 24]

   Number of subjects with dose increase in study medication.

6. Change From Baseline in BPI Severity Score "Pain Right Now" (BPI Item 6) at Week 4 [baseline and week 4]

   Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain right now" (BPI item 6) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain right now".

7. Change From Baseline in BPI Pain Severity Score "Pain at Its Least" (BPI Item 4) at Week 4 [baseline and week 4]

   Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain at its least" (BPI item 4) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its least".

8. Change From Baseline in BPI Pain Severity "Pain at Its Worst" (BPI Item 3) at Week 4 [baseline and week 4]

   Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain at its worst" (BPI item 3) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its worst".

9. Change From Baseline in BPI Pain Severity "Average Pain" (BPI Item 5) at Week 4 [baseline and week 4]

   Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "average pain" (BPI item 5) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "average pain".

10. Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 4 [baseline and week 4]

    Change from baseline in pain severity was assessed using the BPI questionnaire, specifically pain relief (BPI item 8) at week 4. Scores could have ranged from 0 to 100, where 0 = no relief and 100 = complete relief. Positive change from baseline scores indicate improvement in pain relief.

11. Change From Baseline in BPI Pain Severity Score (Mean of BPI Items 3 to 6) at Week 4 [baseline and week 4]

    Change from baseline in BPI pain severity was assessed using the BPI questionnaire (mean of BPI items 3 to 6) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in pain severity.

12. Change From Baseline in BPI Pain Severity "Pain at Its Least" (BPI Item 4) at Week 24 [baseline and week 24]

    Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain at its least" (BPI item 4) at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its least".

13. Change From Baseline in BPI Pain Severity "Average Pain" (BPI Item 5) at Week 24 [baseline and week 24]

    Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "average pain" (BPI item 5) at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "average pain".

14. Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 24 [baseline and week 24]

    Change from baseline in pain severity was assessed using the BPI questionnaire, specifically pain relief (BPI item 8) at week 24. Scores could have ranged from 0 to 100, where 0 = no relief and 100 = complete relief. Positive change from baseline scores indicate improvement in pain relief.

15. Change From Baseline in BPI Pain Severity Score (Mean of BPI Items 3 to 6) at Week 24 [baseline and week 24]

    Change in pain severity was assessed using the BPI questionnaire, specifically average (mean) score of BPI items 3 to 6 (worst pain, least pain, average pain, and pain right now) at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative scores indicate improvement in pain severity.

16. Change From Baseline in BPI Interference Score "Interfered With General Activity" (BPI Item 9a) at Week 4 [baseline and week 4]

    Change from baseline in interference of pain was assessed using the BPI questionnaire, specifically BPI item 9a "pain interfered with general activity" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with general activity".

17. Change From Baseline in Pain Interference "Pain Interfered With Mood" (BPI Item 9b) at Week 4 [baseline and week 4]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9b "pain interfered with mood" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with mood".

18. Change From Baseline in Pain Interference "Pain Interfered With Walking Ability" (BPI Item 9c) at Week 4 [baseline and week 4]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9c "pain interfered with walking ability" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with walking ability".

19. Change From Baseline in Pain Interference "Pain Interfered With Normal Work" (BPI Item 9d) at Week 4 [baseline and week 4]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9d "pain interfered with normal work" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with normal work".

20. Change From Baseline in Pain Interference "Pain Interfered With Relations With Other People" (BPI Item 9e) at Week 4 [baseline and week 4]

    Change from baseline in pain interference was assessed using BPI questionnaire, specifically BPI item 9e "pain interfered with relations with other people" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with relations with other people".

21. Change From Baseline in Pain Interference "Pain Interfered With Sleep" (BPI Item 9f) at Week 4 [baseline and week 4]

    Change from baseline in pain interference was assessed using BPI questionnaire, specifically BPI item 9f "pain interfered with sleep" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 - completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with sleep".

22. Change From Baseline in Pain Interference "Pain Interfered With Enjoyment of Life" (BPI Item 9g) at Week 4 [baseline and week 4]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9g "pain interfered with enjoyment of life" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = interferes completely. Negative change from baseline scores indicate improvement in "pain interfered with enjoyment of life".

23. Change From Baseline in Pain Interference "Pain Interfered With General Activity" (BPI Item 9a) at Week 24 [baseline and week 24]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9a "pain interfered with general activity" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with general activity".

24. Change From Baseline in Pain Interference "Pain Interfered With Mood" (BPI Item 9b) at Week 24 [baseline and week 24]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9b "pain interfered with mood" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with mood".

25. Change From Baseline in Pain Interference "Pain Interfered With Walking Ability" (BPI Item 9c) at Week 24 [baseline and week 24]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9c "pain interfered with walking ability" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with walking ability".

26. Change From Baseline in Pain Interference "Pain Interfered With Normal Work" (BPI Item 9d) at Week 24 [baseline and week 24]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9d "pain interfered with normal work" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with normal work".

27. Change From Baseline in Pain Interference "Pain Interfered With Relations With Other People" (BPI Item 9e) at Week 24 [baseline and week 24]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9e "pain interfered with relations with other people" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with relations with other people".

28. Change From Baseline in Pain Interference "Pain Interfered With Sleep" (BPI Item 9f) at Week 24 [baseline and week 24]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9f "pain interfered with sleep" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with sleep".

29. Change From Baseline in Pain Interference "Pain Interfered With Enjoyment of Life" (BPI Item 9g) at Week 24 [baseline and week 24]

    Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9g "pain interfered with enjoyment of life" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with enjoyment of life".

30. Change From Baseline in BPI Pain Severity, Relief and Interference Scores (Extension Phase) [baseline and week 52]

    Change from baseline in pain severity, pain relief, and pain interference was assessed using the BPI questionnaire at week 52. BPI items 3 to 6, score range 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine; BPI items 9a to 9g, score range from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in pain severity and pain interference. BPI item 8, score range from 0 to 100, where 0 = no relief and 100 = complete relief. Positive change from baseline scores indicate improvement in pain relief.

31. Change From Baseline in Sleep Quality (MOS Index I) at Week 4 [baseline and week 4]

    Change from baseline in sleep quality was assessed using the sleep subscales of the MOS questionnaire, which consists of 12 items; MOS sleep scale index I (average of item 1, 3, 7, 8, 9, and 12) was assessed at week 4. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep quality.

32. Change From Baseline in Sleep Quality (MOS Index II) at Week 4 [baseline and week 4]

    Change from baseline in sleep quality was assessed using the sleep subscales of the MOS questionnaire, which consists of 12 items. MOS index II (average of items 1, 3, 4, 5, 6, 7, 8, 9, and 12) was assessed at week 4. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep quality.

33. Change From Baseline in Sleep Quality (MOS Index II) at Week 24 [baseline and week 24]

    Change from baseline in sleep quality was assessed using the sleep subscales of the MOS questionnaire, which consists of 12 items. MOS index II (average of items 1, 3, 4, 5, 6, 7, 8, 9, and 12) was assessed at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep quality.

34. Change From Baseline in Sleep Quality, Sleep Disturbance at Week 24 [baseline and week 24]

    Change from baseline in sleep quality (sleep disturbance) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep disturbance.

35. Change From Baseline in Sleep Quality, Snoring at Week 24 [baseline and week 24]

    Change from baseline in sleep quality (snoring) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in snoring.

36. Change From Baseline in Sleep Quality, Sleep Shortness of Breath or Headache at Week 24 [baseline and week 24]

    Change from baseline in sleep quality (sleep shortness of breath or headache) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep shortness of breath or headache.

37. Change From Baseline in Sleep Quality, Sleep Adequacy at Week 24 [baseline and week 24]

    Change from baseline in sleep quality (sleep adequacy) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = worst sleep quality and 100 = best sleep quality. Positive change from baseline scores indicate improvement in sleep adequacy.

38. Change From Baseline in Sleep Quality, Sleep Somnolence at Week 24 [baseline and week 24]

    Change from baseline in sleep quality (sleep somnolence) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep somnolence.

39. Change From Baseline in Sleep Quality, Sleep Quantity at Week 24 [baseline and week 24]

    Change from baseline in sleep quality (sleep quantity) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = worst sleep quality and 100 = best sleep quality. Positive change from baseline scores indicate improvement in sleep quantity.

40. Number of Subjects Indicating That They Had Optimal Sleep at Week 24 [baseline and week 24]

    Number of subjects indicating that they had optimal sleep was assessed based on the number of hours of sleep reported on the MOS questionnaire at week 24. Optimal sleep was defined as 7 to 8 hours sleep per night.

41. Change From Baseline in Sleep Quality at Week 52 [baseline and week 52]

    Change from baseline in sleep quality was assessed using the MOS questionnaire at week 52. Score range 0 to 100. For disturbance, snoring, shortness of breath or headache, and somnolence, 0 = best sleep quality and 100 = worst sleep quality; negative change from baseline scores indicate improvement in sleep quality for these measures. For adequacy and quantity, 0 = worst sleep quality and 100 = best sleep quality; positive change from baseline scores indicate improvement in sleep quality for these measures.

42. Number of Subjects Indicating Optimal Sleep at Week 52 [week 52]

    Number of subjects who experienced optimal sleep was assessed based on the number of hours of sleep reported on the MOS questionnaire at week 52. Optimal sleep was defined as 7-8 hours sleep per night.

43. Change From Baseline in Subject Diary Mean Pain Evening, Morning, and All Day Scores at Week 24 [baseline and week 24]

    Change from baseline to week 24 in subject diary evening, morning and all day mean pain scores for pain right now, at its worst, at its least, and average. Subjects rated the severity of pain on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary mean pain scores.

44. Change From Baseline in Subject Diary Mean Pain Score for "Pain at Its Worst" From Morning to Evening at Weeks 4, 8, 12, 16, 20, and 24 [baseline and weeks 4, 8, 12, 16, 20, and 24]

    Change from baseline in subject diary mean pain score "pain at its worst" from morning to evening at weeks 4, 8, 12, 16, 20, and 24. Subjects rated the severity of "pain right now" on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary mean pain score "pain at its worst".

45. Number of Subjects With Dose Escalation at Week 4 (ITT Population) [week 4]

    The number of subjects with dose increase in study medication was assessed at week 4.

46. Number of Subjects With Dose Escalation at Week 24 (ITT Population) [week 24]

    The number of subjects with dose increase in study medication was assessed at week 24.

47. Change From Baseline in Quality of Life (QoL) "Bodily Pain" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the Short Form (SF)-36 QoL questionnaire, specifically the SF-36 bodily pain index. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in bodily pain.

48. Change From Baseline in QoL "General Health Perceptions" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 general health perceptions score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in general health perceptions.

49. Change From Baseline in QoL "Health Transition" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 health transition score at week 4. Scores could range from 0 to 100, with higher scores indicating a better QoL. Positive change from baseline scores indicate improvement in health transition.

50. Change From Baseline in QoL "Mental Health" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 mental health score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in mental health score.

51. Change From Baseline in QoL "Physical Functioning" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 physical functioning score at week 4. Scores could range from 0 to 100, with high scores indicating a better QoL. Positive change from baseline scores indicate improvement in physical functioning.

52. Change From Baseline in QoL "Role Emotional" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 "role emotional" score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in "role emotional".

53. Change From Baseline in QoL "Role Physical" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 role physical score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in role physical.

54. Change From Baseline in QoL "Social Functioning" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 social functioning score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in social functioning.

55. Change From Baseline in QoL "Vitality" at Week 4 [baseline and week 4]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 vitality score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in vitality.

56. Change From Baseline in QoL "Bodily Pain" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 bodily pain index score at week 24. Score could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in bodily pain.

57. Change From Baseline in QoL "General Health Perceptions" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 general health perceptions at week 24. Scores could range from 0 to 100 with a higher score indicating a better QoL. Positive change from baseline scores indicate improvement in health perceptions.

58. Change From Baseline in QoL "Health Transition" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 health transition score at week 24. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in health transition.

59. Change From Baseline in QoL "Mental Health" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 mental health score at week 24. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline score indicates improvement in mental health.

60. Change From Baseline in QoL "Physical Functioning" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 physical functioning score at week 24. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in physical functioning.

61. Change From Baseline in QoL "Role Emotional" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 "role emotional" score at week 24. Scores could range from 0 to 100 with a higher score indicating a better QoL. Positive change from baseline scores indicate improvement in "role emotional."

62. Change From Baseline in QoL "Role Physical" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 role physical score at week 24. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in role physical.

63. Change From Baseline in QoL "Social Functioning" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 social functioning score at week 24. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in social functioning.

64. Change From Baseline in QoL "Vitality" at Week 24 [baseline and week 24]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 vitality score at week 24. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in vitality.

65. Change From Baseline in QoL at Week 52 [baseline and week 52]

    Change from baseline in QoL was assessed using the SF-36 QoL questionnaire at week 52. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in QoL.

66. Clinical Global Assessment of Efficacy [weeks 4, 24, and 52]

    Overall clinical efficacy was assessed by the Investigator using the following global ratings: very good, good, moderate, poor, or very poor, at weeks 4, 24, and 52.

67. Change in Dose of Study Treatment [weeks 4, 24, and 52]

    Number of subjects with change in dose of study treatment was assessed at weeks 4, 24, and 52.

68. Change in Dose of Study Treatment During Titration Phase (First 4 Weeks of Study) and Overall Treatment Phase I (First 24 Weeks of Study) [weeks 4 and 24]

    Number of subejcts with change in dose of study treatment was assessed and stratified by time on study, at least 4 weeks versus dropped out at highest dose before week 4, at weeks 4 and 24.

69. Number of Drop-outs [baseline to week 24 (core); week 24 to week 52 (extension)]

    Number of drop-outs according to reasons for drop-out and due to inefficacy at maximal dosage was assessed at weeks 24 and 52.

70. Number of Days With add-on Pain Medication [week 24]

    Number of days with add-on pain medication during the first 24 weeks of the study was assessed at week 24.

71. Amount of add-on Pain Medication [24 weeks]

    Total amount of add-on pain medication (paracetamol) for the first 24 weeks was assessed at week 24.

72. Mode and Convenience of Drug Intake. [weeks 4, 24, and 52]

    Subjects filled out a questionnaire based on the mode and convenience of drug intake and could rate their responses as very convenient, convenient, neither convenient or inconvenient, inconvenient, and very inconvenient.

73. Resource Utilization of Pain Management [week 24]

    Resource utilization was defined as the number of additional visits including additional telephone visits during the treatment period. This was assessed at week 24.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult patients with chronic noncancer pain severe enough to require continuous opioid therapy (a score of at least 5 in "pain right now" on a 11 point numeric rating scale) who have never received an opioid or are currently treated with a weak opioid, and who experience insufficient pain control.

Exclusion Criteria:

• Patients who have been treated with strong opioids (including hydromorphone and oxycodone) within the last 4 weeks prior to study inclusion or who will probably undergo any treatment (e.g. neurological techniques, surgery) within the next 6 months, which may abruptly alter degree or nature of pain experienced

• patients with a history of disease(s), current illness, or therapy which would preclude them from participation in the study

• and patients who are pregnant or nursing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Brno		Czech Republic
2		Plzen		Czech Republic
3		Praha 5		Czech Republic
4		Praha 8		Czech Republic
5		Esbjerg N/A		Denmark
6		København		Denmark
7		Nyborg N/A		Denmark
8		Svendborg N/A		Denmark
9		Vejle		Denmark
10		Amiens Cedex 1		France
11		Bois Guillaume		France
12		Lille		France
13		Paris		France
14		Berlin		Germany
15		Drensteinfurt		Germany
16		Dresden		Germany
17		Duderstadt		Germany
18		Frankfurt		Germany
19		Giessen		Germany
20		Göppingen		Germany
21		Hamburg		Germany
22		Herne		Germany
23		Jena		Germany
24		Kiel		Germany
25		Kÿln		Germany
26		Ludwigshafen		Germany
27		Mannheim		Germany
28		Nürnberg		Germany
29		Regensburg		Germany
30		Rodgau		Germany
31		Wiesbaden		Germany
32		Bodø		Norway
33		Lørenskog		Norway
34		Oslo N/A		Norway
35		Oslo		Norway
36		Gdansk		Poland
37		Krakow		Poland
38		Lublin		Poland
39		Warszawa		Poland
40		Wroclaw		Poland
41		Banska Bystrica		Slovakia
42		Bratislava		Slovakia
43		Martin		Slovakia
44		Prešov		Slovakia
45		Ljubljana		Slovenia
46		Maribor		Slovenia
47		Slovenj Gradec		Slovenia
48		Göteborg		Sweden
49		Jönköping		Sweden
50		Kristianstad		Sweden
51		Linköping		Sweden
52		Aarau		Switzerland
53		Basel		Switzerland
54		Lausanne		Switzerland

Sponsors and Collaborators

• Janssen Pharmaceutica N.V., Belgium

Investigators

• Study Director: Janssen Pharmaceutica N.V. Clinical Trial, Janssen Pharmaceutica N.V.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Pharmaceutica N.V., Belgium
• ClinicalTrials.gov Identifier: NCT00261495
• Other Study ID Numbers: CR002374; OROS-ANA-3001; 2004-005187-24
• First Posted: Dec 5, 2005
• Last Update Posted: Jun 3, 2014
• Last Verified: May 1, 2014

• Keywords provided by Janssen Pharmaceutica N.V., Belgium: chronic noncancer pain; pain; analgesia; analgesic opioid; oxycodone; hydromorphone
• Additional relevant MeSH terms: Oxycodone; Hydromorphone

Study Results

Participant Flow

Recruitment Details	Study conducted in 11 countries (Czech Republic, Denmark, France, Germany, Italy, Norway, Poland, Slovakia, Slovenia, Sweden, and Switzerland). 63 study centres randomized subjects and 1 centre screened 1 subject but did not randomize. Recruitment period: 15 March 2006 (first patient in) to 31 March 2007 (last patient in).

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Period Title: Titration Phase (Weeks 0 to 4)
STARTED	254	250
COMPLETED	206	185
NOT COMPLETED	48	65
Period Title: Titration Phase (Weeks 0 to 4)
STARTED	206	185
COMPLETED	140	137
NOT COMPLETED	66	48
Period Title: Titration Phase (Weeks 0 to 4)
STARTED	60	52
COMPLETED	50	47
NOT COMPLETED	10	5

Baseline Characteristics

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone	Total
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)	Total of all reporting groups
Overall Participants	254	250	504
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.1 (13.06)	58.0 (12.82)	57.5 (12.93)
Sex: Female, Male (Count of Participants)
Female	142 55.9%	152 60.8%	294 58.3%
Male	112 44.1%	98 39.2%	210 41.7%
Region of Enrollment (participants) [Number]
Czech Republic	34 13.4%	18 7.2%	52 10.3%
Denmark	19 7.5%	20 8%	39 7.7%
France	22 8.7%	18 7.2%	40 7.9%
Germany	83 32.7%	80 32%	163 32.3%
Italy	17 6.7%	21 8.4%	38 7.5%
Norway	18 7.1%	18 7.2%	36 7.1%
Poland	28 11%	34 13.6%	62 12.3%
Slovakia	11 4.3%	11 4.4%	22 4.4%
Slovenia	3 1.2%	5 2%	8 1.6%
Sweden	14 5.5%	19 7.6%	33 6.5%
Switzerland	5 2%	6 2.4%	11 2.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Brief Pain Inventory (BPI) Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Per Protocol [PP] Population)
Description	Assessment of non-inferiority of OROS hydromorphone compared with sustained release (SR) oxycodone with regard to pain control by measuring the change from baseline in pain severity, using BPI item 6 "pain right now" score at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain right now".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

PP population (all randomized subjects who took the study medication at least once, who had post-baseline efficacy data, and who were without major protocol violation)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	115	108
Mean (Standard Deviation) [Units on a scale]	-2.8 (2.04)	-3.2 (2.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Null hypothesis: Difference in change from baseline with OROS hydromorphone compared with SR oxycodone was less than or equal to 1. Alternative hypothesis: Difference in change from baseline with OROS hydromorphone compared with SR oxycodone was greater than 1. Sample size needed to detect a clinically significant difference of 1 was 151 per treatment arm (standard deviation = 2.4, significance level 0.025 one-sided, based on 90% power).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Tested using 95% confidence interval approach. The non-inferiority margin was 1.
Statistical Test of Hypothesis	p-Value	0.011
	Comments	Statistical significance level was 0.05. Two-sided 95% CI of the treatment difference based on LS means & error terms obtained from ANCOVA (covariate: baseline; factors: country, previous pain treatment, underlying disease, and treatment).
	Method	ANCOVA
	Comments	If the right side of CI<1 then the null hypothesis was rejected in favour of the alternative, and non-inferiority of OROS hydromorphone was concluded.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.29
	Confidence Interval	() 95%; -0.27 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS mean difference has been presented, which was calculated as hydromorphone minus oxycodone.

2. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity Sub-score "Pain at Its Worst" (BPI Item 3) at Week 24 (ITT Population)
Description	Change from baseline to week 24 in BPI pain severity, pain at its worst (BPI item 3) assessed using the BPI questionnaire. Score values ranges from 0 (no pain) to 10 (pain as bad as you can imagine). Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its worst".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.9 (2.20)	-1.9 (2.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Null hypothesis: Difference in change from baseline between hydromorphone and oxycodone was equal to zero. Alternative hypothesis: Difference in change from baseline between hydromorphone and oxycodone was not equal to zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.706
	Comments	A two-sided significance level of 0.05 was used. A closed hierarchical testing procedure was used to control the overall Type I error. Procedure was stopped here, subsequent tests were exploratory in nature.
	Method	ANCOVA
	Comments	Superiority of OROS hydromorphone compared to SR oxycodone was evaluated.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.08
	Confidence Interval	() 95%; -0.32 to 0.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

3. Primary Outcome

Title	Change From Baseline in BPI Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Intent to Treat [ITT] Population)
Description	Assessment of non-inferiority of OROS hydromorphone compared with SR oxycodone with regard to pain control by measuring the change from baseline in pain severity, using BPI item 6 "pain right now" score at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain right now".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	233	223
Mean (Standard Deviation) [Units on a scale]	-2.1 (2.43)	-2.1 (2.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Null hypothesis: Difference in change from baseline with OROS hydromorphone compared with SR oxycodone was less than or equal to 1. Alternative hypothesis: Difference in change from baseline with OROS hydromorphone compared with SR oxycodone was greater than 1. Sample size needed to detect a clinically significant difference of 1 was 151 per treatment arm (standard deviation = 2.4, significance level 0.025 one-sided, based on 90% power).
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Tested using 95% confidence interval approach. The non-inferiority margin was 1.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical significance level was 0.05. Two-sided 95% CI of the treatment difference based on LS means & error terms obtained from ANCOVA (covariate: baseline; factors: country, previous pain treatment, underlying disease, and treatment).
	Method	ANCOVA
	Comments	If the right side of CI<1 then the null hypothesis was rejected in favour of the alternative, and non-inferiority of OROS hydromorphone was concluded.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.12
	Confidence Interval	() 95%; -0.53 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

4. Secondary Outcome

Title	Change From Baseline in Sleep Quality at Week 24
Description	Change from baseline in sleep quality was assessed using the Medical Outcomes Study (MOS) questionnaire at week 24, specifically the sleep subscale index I. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improved sleep quality.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-8.8 (18.44)	-6.2 (18.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Null hypothesis: Difference in change from baseline between hydromorphone and oxycodone was equal to zero. Alternative hypothesis: Difference in change from baseline between hydromorphone and oxycodone was not equal to zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.065
	Comments	A two-sided significance level of 0.05 was used. A closed hierarchical testing procedure was used to control the overall Type I error. Procedure has been stopped, test is exploratory in nature.
	Method	ANCOVA
	Comments	Superiority of OROS hydromorphone compared to SR oxycodone was evaluated.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.87
	Confidence Interval	() 95%; -5.94 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

5. Secondary Outcome

Title	Change From Baseline in Subject Diary Evening Mean Pain Score "Pain Right Now" at Week 24
Description	Change from baseline to week 24 in subject diary evening mean pain score "pain right now". Subjects rated the severity of "pain right now" on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary evening mean pain score "pain right now".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-2.2 (2.08)	-2.0 (2.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Null hypothesis: Difference in change from baseline between hydromorphone and oxycodone was equal to zero. Alternative hypothesis: Difference in change from baseline between hydromorphone and oxycodone was not equal to zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.348
	Comments	A two-sided significance level of 0.05 was used. A closed hierarchical testing approach was used to control the overall Type I error. Procedure has been stopped, test is exploratory in nature.
	Method	ANCOVA
	Comments	Superiority of OROS hydromorphone compared to SR oxycodone was evaluated.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.20
	Confidence Interval	() 95%; -0.62 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference was calculated: hydromorphone minus oxycodone

6. Secondary Outcome

Title	Change From Baseline in Subject Diary Morning Mean Pain Score "Pain Right Now" at Week 24
Description	Change from baseline to week 24 in subject diary morning mean pain score "pain right now". Subjects rated the severity of "pain right now" on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary evening mean pain score "pain right now".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-2.0 (2.33)	-2.0 (2.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Null hypothesis: Difference in change from baseline between hydromorphone and oxycodone was equal to zero. Alternative hypothesis: Difference in change from baseline between hydromorphone and oxycodone was not equal to zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.616
	Comments	A two-sided significance level of 0.05 was used. A closed hierarchical testing approach was used to control the overall Type I error. Procedure has been stopped, test is exploratory in nature.
	Method	ANCOVA
	Comments	Superiority of OROS hydromorphone compared to SR oxycodone was evaluated.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	() 95%; -0.54 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference was calculated: hydromorphone minus oxycodone

7. Secondary Outcome

Title	Number of Subjects With Dose Escalation
Description	Number of subjects with dose increase in study medication.
Time Frame	week 4 and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	203	182
Yes	27	34
No	176	148

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Null hypothesis: There is no association between study medication and dose escalation. Alternative hypothesis: There is an association between study medication and dose escalation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.249
	Comments	A two-sided significance level of 0.05 was used. A closed hierarchical testing approach was used to control the overall Type I error. Hierarchical testing procedure has been stopped, test is exploratory in nature.
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel Chi-squared statistic stratified for country was used.

8. Secondary Outcome

Title	Change From Baseline in BPI Severity Score "Pain Right Now" (BPI Item 6) at Week 4
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain right now" (BPI item 6) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain right now".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-2.2 (2.34)	-2.6 (2.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.050
	Comments	0.05 two-sided testing, exploratory comparison
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.42
	Confidence Interval	() 95%; -0.00 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

9. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity Score "Pain at Its Least" (BPI Item 4) at Week 4
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain at its least" (BPI item 4) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its least".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.3 (2.03)	-1.8 (2.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.30
	Confidence Interval	() 95%; -0.06 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

10. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity "Pain at Its Worst" (BPI Item 3) at Week 4
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain at its worst" (BPI item 3) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its worst".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.8 (2.14)	-2.1 (1.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.058
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.39
	Confidence Interval	() 95%; -0.01 to 0.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

11. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity "Average Pain" (BPI Item 5) at Week 4
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "average pain" (BPI item 5) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "average pain".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.9 (1.89)	-2.1 (2.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.210
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.23
	Confidence Interval	() 95%; -0.13 to 0.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hdromorphone minus oxycodone

12. Secondary Outcome

Title	Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 4
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically pain relief (BPI item 8) at week 4. Scores could have ranged from 0 to 100, where 0 = no relief and 100 = complete relief. Positive change from baseline scores indicate improvement in pain relief.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	13.8 (25.15)	15.2 (26.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.941
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.18
	Confidence Interval	() 95%; -4.87 to 4.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

13. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity Score (Mean of BPI Items 3 to 6) at Week 4
Description	Change from baseline in BPI pain severity was assessed using the BPI questionnaire (mean of BPI items 3 to 6) at week 4. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in pain severity.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.7 (1.76)	-2.0 (1.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.073
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.31
	Confidence Interval	() 95%; -0.03 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

14. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity "Pain at Its Least" (BPI Item 4) at Week 24
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "pain at its least" (BPI item 4) at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "pain at its least".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.3 (2.23)	-1.4 (2.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.431
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.15
	Confidence Interval	() 95%; -0.52 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

15. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity "Average Pain" (BPI Item 5) at Week 24
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically "average pain" (BPI item 5) at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative change from baseline scores indicate improvement in "average pain".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.8 (2.07)	-1.7 (2.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.835
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.04
	Confidence Interval	() 95%; -0.40 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

16. Secondary Outcome

Title	Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 24
Description	Change from baseline in pain severity was assessed using the BPI questionnaire, specifically pain relief (BPI item 8) at week 24. Scores could have ranged from 0 to 100, where 0 = no relief and 100 = complete relief. Positive change from baseline scores indicate improvement in pain relief.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	8.6 (29.32)	11.5 (28.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.837
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.51
	Confidence Interval	() 95%; -5.36 to 4.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

17. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity Score (Mean of BPI Items 3 to 6) at Week 24
Description	Change in pain severity was assessed using the BPI questionnaire, specifically average (mean) score of BPI items 3 to 6 (worst pain, least pain, average pain, and pain right now) at week 24. Scores could have ranged from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. Negative scores indicate improvement in pain severity.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.6 (1.91)	-1.7 (2.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.04
	Confidence Interval	() 95%; -0.38 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

18. Secondary Outcome

Title	Change From Baseline in BPI Interference Score "Interfered With General Activity" (BPI Item 9a) at Week 4
Description	Change from baseline in interference of pain was assessed using the BPI questionnaire, specifically BPI item 9a "pain interfered with general activity" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with general activity".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.6 (2.14)	-1.9 (2.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.143
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.30
	Confidence Interval	() 95%; -0.10 to 0.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

19. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Mood" (BPI Item 9b) at Week 4
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9b "pain interfered with mood" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with mood".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.7 (2.32)	-1.9 (2.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.345
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.21
	Confidence Interval	() 95%; -0.23 to 0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

20. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Walking Ability" (BPI Item 9c) at Week 4
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9c "pain interfered with walking ability" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with walking ability".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.2 (2.63)	-1.5 (2.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.552
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.14
	Confidence Interval	() 95%; -0.33 to 0.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

21. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Normal Work" (BPI Item 9d) at Week 4
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9d "pain interfered with normal work" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with normal work".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.4 (2.40)	-2.0 (2.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.042
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.47
	Confidence Interval	() 95%; 0.02 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

22. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Relations With Other People" (BPI Item 9e) at Week 4
Description	Change from baseline in pain interference was assessed using BPI questionnaire, specifically BPI item 9e "pain interfered with relations with other people" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with relations with other people".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.1 (2.56)	-1.4 (2.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.171
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.33
	Confidence Interval	() 95%; -0.14 to 0.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

23. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Sleep" (BPI Item 9f) at Week 4
Description	Change from baseline in pain interference was assessed using BPI questionnaire, specifically BPI item 9f "pain interfered with sleep" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 - completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with sleep".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-2.1 (2.34)	-2.3 (3.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.17
	Confidence Interval	() 95%; -0.31 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

24. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Enjoyment of Life" (BPI Item 9g) at Week 4
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9g "pain interfered with enjoyment of life" at week 4. Scores could have ranged from 0 to 10, where 0 = does not interfere and 10 = interferes completely. Negative change from baseline scores indicate improvement in "pain interfered with enjoyment of life".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.6 (2.62)	-1.9 (2.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.359
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.23
	Confidence Interval	() 95%; -0.26 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

25. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With General Activity" (BPI Item 9a) at Week 24
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9a "pain interfered with general activity" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with general activity".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.6 (2.42)	-1.6 (2.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.611
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.11
	Confidence Interval	() 95%; -0.52 to 0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

26. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Mood" (BPI Item 9b) at Week 24
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9b "pain interfered with mood" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with mood".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.4 (2.85)	-1.3 (2.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.526
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.15
	Confidence Interval	() 95%; -0.60 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

27. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Walking Ability" (BPI Item 9c) at Week 24
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9c "pain interfered with walking ability" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with walking ability".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.1 (2.75)	-1.2 (2.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.769
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.06
	Confidence Interval	() 95%; -0.49 to 0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

28. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Normal Work" (BPI Item 9d) at Week 24
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9d "pain interfered with normal work" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with normal work".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.3 (2.63)	-1.4 (2.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.843
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.04
	Confidence Interval	() 95%; -0.40 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

29. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Relations With Other People" (BPI Item 9e) at Week 24
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9e "pain interfered with relations with other people" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with relations with other people".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-0.7 (2.92)	-0.9 (2.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.977
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.45 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

30. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Sleep" (BPI Item 9f) at Week 24
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9f "pain interfered with sleep" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with sleep".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.4 (2.76)	-1.5 (3.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.977
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.01
	Confidence Interval	() 95%; -0.47 to 0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

31. Secondary Outcome

Title	Change From Baseline in Pain Interference "Pain Interfered With Enjoyment of Life" (BPI Item 9g) at Week 24
Description	Change from baseline in pain interference was assessed using the BPI questionnaire, specifically BPI item 9g "pain interfered with enjoyment of life" at week 24. Scores could have ranged from 0 to 10, where 0 = does not interfere to 10 = completely interferes. Negative change from baseline scores indicate improvement in "pain interfered with enjoyment of life".
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.2 (2.91)	-1.3 (3.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.902
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.03
	Confidence Interval	() 95%; -0.51 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

32. Secondary Outcome

Title	Change From Baseline in BPI Pain Severity, Relief and Interference Scores (Extension Phase)
Description	Change from baseline in pain severity, pain relief, and pain interference was assessed using the BPI questionnaire at week 52. BPI items 3 to 6, score range 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine; BPI items 9a to 9g, score range from 0 to 10, where 0 = does not interfere and 10 = completely interferes. Negative change from baseline scores indicate improvement in pain severity and pain interference. BPI item 8, score range from 0 to 100, where 0 = no relief and 100 = complete relief. Positive change from baseline scores indicate improvement in pain relief.
Time Frame	baseline and week 52

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Pain severity, BPI items 3 to 6	-2.4 (1.67)	-2.4 (2.13)
Pain relief, BPI item 8	17.7 (26.36)	23.6 (25.46)
Pain right now, BPI item 6	-2.9 (2.07)	-2.8 (2.16)
Pain at its worst, BPI item 3	-2.8 (2.07)	-2.4 (2.29)
Pain at its least, BPI item 4	-1.9 (2.14)	-2.3 (2.59)
Average pain, BPI item 5	-2.6 (1.78)	-2.6 (2.21)
Pain interfered general activity, BPI item 9a	-2.5 (2.28)	-2.6 (2.40)
Pain interfered mood, BPI item 9b	-2.3 (2.42)	-2.7 (3.12)
Pain interfered walking ability, BPI item 9c	-2.3 (2.10)	-2.5 (2.89)
Pain interfered normal work, BPI item 9d	-2.9 (2.64)	-3.2 (2.63)
Pain interfered relation other people, BPI item 9e	-1.6 (2.56)	-1.9 (3.34)
BPI pain interfered sleep, BPI item 9f	-2.4 (2.61)	-3.0 (3.02)
BPI pain interfered enjoyment of life, BPI item 9g	-2.4 (2.63)	-2.6 (3.32)

33. Secondary Outcome

Title	Change From Baseline in Sleep Quality (MOS Index I) at Week 4
Description	Change from baseline in sleep quality was assessed using the sleep subscales of the MOS questionnaire, which consists of 12 items; MOS sleep scale index I (average of item 1, 3, 7, 8, 9, and 12) was assessed at week 4. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep quality.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-10.6 (17.61)	-8.7 (18.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.169
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.36
	Confidence Interval	() 95%; -5.74 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

34. Secondary Outcome

Title	Change From Baseline in Sleep Quality (MOS Index II) at Week 4
Description	Change from baseline in sleep quality was assessed using the sleep subscales of the MOS questionnaire, which consists of 12 items. MOS index II (average of items 1, 3, 4, 5, 6, 7, 8, 9, and 12) was assessed at week 4. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep quality.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-10.5 (16.40)	-9.0 (17.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.245
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.89
	Confidence Interval	() 95%; -5.09 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

35. Secondary Outcome

Title	Change From Baseline in Sleep Quality (MOS Index II) at Week 24
Description	Change from baseline in sleep quality was assessed using the sleep subscales of the MOS questionnaire, which consists of 12 items. MOS index II (average of items 1, 3, 4, 5, 6, 7, 8, 9, and 12) was assessed at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep quality.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-8.9 (17.28)	-6.5 (16.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.071
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.64
	Confidence Interval	() 95%; -5.51 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

36. Secondary Outcome

Title	Change From Baseline in Sleep Quality, Sleep Disturbance at Week 24
Description	Change from baseline in sleep quality (sleep disturbance) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep disturbance.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-13.1 (22.77)	-11.7 (22.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.03
	Confidence Interval	() 95%; -5.85 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

37. Secondary Outcome

Title	Change From Baseline in Sleep Quality, Snoring at Week 24
Description	Change from baseline in sleep quality (snoring) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in snoring.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.0 (22.04)	-4.1 (21.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.205
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.41
	Confidence Interval	() 95%; -1.32 to 6.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

38. Secondary Outcome

Title	Change From Baseline in Sleep Quality, Sleep Shortness of Breath or Headache at Week 24
Description	Change from baseline in sleep quality (sleep shortness of breath or headache) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep shortness of breath or headache.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-5.3 (28.44)	-0.1 (24.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.107
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.35
	Confidence Interval	() 95%; -7.43 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

39. Secondary Outcome

Title	Change From Baseline in Sleep Quality, Sleep Adequacy at Week 24
Description	Change from baseline in sleep quality (sleep adequacy) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = worst sleep quality and 100 = best sleep quality. Positive change from baseline scores indicate improvement in sleep adequacy.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	9.1 (28.10)	7.3 (26.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.60
	Confidence Interval	() 95%; -2.80 to 6.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

40. Secondary Outcome

Title	Change From Baseline in Sleep Quality, Sleep Somnolence at Week 24
Description	Change from baseline in sleep quality (sleep somnolence) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = best sleep quality and 100 = worst sleep quality. Negative change from baseline scores indicate improvement in sleep somnolence.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-1.6 (21.70)	3.0 (20.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.16
	Confidence Interval	() 95%; -7.67 to -0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

41. Secondary Outcome

Title	Change From Baseline in Sleep Quality, Sleep Quantity at Week 24
Description	Change from baseline in sleep quality (sleep quantity) was assessed using the MOS questionnaire at week 24. Score range 0 to 100, where 0 = worst sleep quality and 100 = best sleep quality. Positive change from baseline scores indicate improvement in sleep quantity.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	0.4 (1.86)	0.5 (1.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.880
	Comments	0.05 two-sided test
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.30 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

42. Secondary Outcome

Title	Number of Subjects Indicating That They Had Optimal Sleep at Week 24
Description	Number of subjects indicating that they had optimal sleep was assessed based on the number of hours of sleep reported on the MOS questionnaire at week 24. Optimal sleep was defined as 7 to 8 hours sleep per night.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	249	242
Yes	83	71
No	166	171

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.320
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

43. Secondary Outcome

Title	Change From Baseline in Sleep Quality at Week 52
Description	Change from baseline in sleep quality was assessed using the MOS questionnaire at week 52. Score range 0 to 100. For disturbance, snoring, shortness of breath or headache, and somnolence, 0 = best sleep quality and 100 = worst sleep quality; negative change from baseline scores indicate improvement in sleep quality for these measures. For adequacy and quantity, 0 = worst sleep quality and 100 = best sleep quality; positive change from baseline scores indicate improvement in sleep quality for these measures.
Time Frame	baseline and week 52

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
MOS sleep disturbance	-17.6 (22.44)	-20.1 (23.17)
MOS snoring	-2.5 (23.01)	-4.7 (23.86)
MOS sleep shortness of breath or headache	-8.4 (19.89)	-7.8 (21.94)
MOS sleep adequacy	12.3 (27.06)	11.9 (30.74)
MOS sleep somnolence	-6.5 (20.49)	1.8 (21.54)
MOS sleep quantity	0.5 (2.27)	0.5 (1.25)

44. Secondary Outcome

Title	Number of Subjects Indicating Optimal Sleep at Week 52
Description	Number of subjects who experienced optimal sleep was assessed based on the number of hours of sleep reported on the MOS questionnaire at week 52. Optimal sleep was defined as 7-8 hours sleep per night.
Time Frame	week 52

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	55	49
Yes	27	19
No	28	30

45. Secondary Outcome

Title	Change From Baseline in Subject Diary Mean Pain Evening, Morning, and All Day Scores at Week 24
Description	Change from baseline to week 24 in subject diary evening, morning and all day mean pain scores for pain right now, at its worst, at its least, and average. Subjects rated the severity of pain on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary mean pain scores.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Evening worst pain	-2.2 (2.32)	-2.1 (2.31)
Evening least pain	-1.6 (2.28)	-1.4 (2.36)
Evening average pain	-2.0 (2.12)	-1.8 (2.22)
Morning worst pain	-1.9 (2.38)	-2.1 (2.34)
Morning least pain	-1.5 (2.44)	-1.2 (2.44)
Morning average pain	-1.7 (2.20)	-1.8 (2.30)
All day worst pain	-2.1 (2.11)	-2.1 (2.09)
All day least pain	-1.5 (2.21)	-1.3 (2.22)
All day average pain	-1.8 (2.00)	-1.8 (2.08)
All day pain right now	-2.1 (2.05)	-2.0 (2.20)

46. Secondary Outcome

Title	Change From Baseline in Subject Diary Mean Pain Score for "Pain at Its Worst" From Morning to Evening at Weeks 4, 8, 12, 16, 20, and 24
Description	Change from baseline in subject diary mean pain score "pain at its worst" from morning to evening at weeks 4, 8, 12, 16, 20, and 24. Subjects rated the severity of "pain right now" on a 10 point numeric scale, with 0 being the least pain and 10 being the most pain. Negative change from baseline scores indicate improvement in subject diary mean pain score "pain at its worst".
Time Frame	baseline and weeks 4, 8, 12, 16, 20, and 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Baseline	0.7 (1.93)	0.4 (1.88)
Week 4	0.5 (1.30)	0.4 (1.22)
Week 8	0.4 (1.23)	0.4 (1.42)
Week 12	0.3 (1.23)	0.3 (1.26)
Week 16	0.2 (1.08)	0.2 (1.28)
Week 20	0.3 (1.13)	0.2 (1.14)
Week 24	0.3 (1.23)	0.3 (1.07)

47. Secondary Outcome

Title	Number of Subjects With Dose Escalation at Week 4 (ITT Population)
Description	The number of subjects with dose increase in study medication was assessed at week 4.
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Yes	175	166
No	79	84

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.575
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

48. Secondary Outcome

Title	Number of Subjects With Dose Escalation at Week 24 (ITT Population)
Description	The number of subjects with dose increase in study medication was assessed at week 24.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	203	182
Yes	146	145
No	57	37

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.807
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

49. Secondary Outcome

Title	Change From Baseline in Quality of Life (QoL) "Bodily Pain" at Week 4
Description	Change from baseline in QoL was assessed using the Short Form (SF)-36 QoL questionnaire, specifically the SF-36 bodily pain index. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in bodily pain.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	13.7 (18.10)	16.7 (18.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.118
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.61
	Confidence Interval	() 95%; -5.88 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

50. Secondary Outcome

Title	Change From Baseline in QoL "General Health Perceptions" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 general health perceptions score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in general health perceptions.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	3.9 (14.43)	5.0 (16.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.956
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.08
	Confidence Interval	() 95%; -3.08 to 2.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

51. Secondary Outcome

Title	Change From Baseline in QoL "Health Transition" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 health transition score at week 4. Scores could range from 0 to 100, with higher scores indicating a better QoL. Positive change from baseline scores indicate improvement in health transition.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-0.4 (1.08)	-0.5 (0.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.299
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.09
	Confidence Interval	() 95%; -0.08 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

52. Secondary Outcome

Title	Change From Baseline in QoL "Mental Health" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 mental health score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in mental health score.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	6.2 (15.76)	6.6 (17.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.471
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.13
	Confidence Interval	() 95%; -4.20 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxymorphone

53. Secondary Outcome

Title	Change From Baseline in QoL "Physical Functioning" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 physical functioning score at week 4. Scores could range from 0 to 100, with high scores indicating a better QoL. Positive change from baseline scores indicate improvement in physical functioning.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	8.7 (17.05)	5.4 (16.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.84
	Confidence Interval	() 95%; 0.48 to 7.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

54. Secondary Outcome

Title	Change From Baseline in QoL "Role Emotional" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 "role emotional" score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in "role emotional".
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	9.9 (43.25)	4.7 (48.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.556
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.40
	Confidence Interval	() 95%; -5.61 to 10.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

55. Secondary Outcome

Title	Change From Baseline in QoL "Role Physical" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 role physical score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in role physical.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	13.2 (36.84)	16.9 (36.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.551
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.12
	Confidence Interval	() 95%; -9.11 to 4.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

56. Secondary Outcome

Title	Change From Baseline in QoL "Social Functioning" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 social functioning score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in social functioning.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	10.5 (25.33)	12.9 (26.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.207
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.98
	Confidence Interval	() 95%; -7.63 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

57. Secondary Outcome

Title	Change From Baseline in QoL "Vitality" at Week 4
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 vitality score at week 4. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in vitality.
Time Frame	baseline and week 4

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	6.4 (16.92)	9.2 (17.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.123
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.46
	Confidence Interval	() 95%; -5.60 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

58. Secondary Outcome

Title	Change From Baseline in QoL "Bodily Pain" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 bodily pain index score at week 24. Score could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in bodily pain.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	10.6 (21.04)	11.9 (19.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.602
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.90
	Confidence Interval	() 95%; -4.27 to 2.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

59. Secondary Outcome

Title	Change From Baseline in QoL "General Health Perceptions" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 general health perceptions at week 24. Scores could range from 0 to 100 with a higher score indicating a better QoL. Positive change from baseline scores indicate improvement in health perceptions.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	2.1 (17.04)	2.2 (16.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.647
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.65
	Confidence Interval	() 95%; -2.14 to 3.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

60. Secondary Outcome

Title	Change From Baseline in QoL "Health Transition" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 health transition score at week 24. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in health transition.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	-0.2 (1.03)	-0.1 (0.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.627
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.03
	Confidence Interval	() 95%; -0.17 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

61. Secondary Outcome

Title	Change From Baseline in QoL "Mental Health" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 mental health score at week 24. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline score indicates improvement in mental health.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	2.6 (19.30)	2.6 (18.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.414
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.30
	Confidence Interval	() 95%; -4.45 to 1.84
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

62. Secondary Outcome

Title	Change From Baseline in QoL "Physical Functioning" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 physical functioning score at week 24. Scores could range from 0 to 100, with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in physical functioning.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	7.7 (19.09)	4.4 (15.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.05
	Confidence Interval	() 95%; 0.94 to 7.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

63. Secondary Outcome

Title	Change From Baseline in QoL "Role Emotional" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 "role emotional" score at week 24. Scores could range from 0 to 100 with a higher score indicating a better QoL. Positive change from baseline scores indicate improvement in "role emotional."
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	0.40 (47.71)	-1.5 (47.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.955
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.21
	Confidence Interval	() 95%; -7.20 to 7.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

64. Secondary Outcome

Title	Change From Baseline in QoL "Role Physical" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 role physical score at week 24. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in role physical.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	8.8 (37.80)	9.9 (34.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.669
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.31
	Confidence Interval	() 95%; -4.72 to 7.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

65. Secondary Outcome

Title	Change From Baseline in QoL "Social Functioning" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 social functioning score at week 24. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in social functioning.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	6.6 (27.81)	5.0 (26.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.595
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.17
	Confidence Interval	() 95%; -3.15 to 5.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

66. Secondary Outcome

Title	Change From Baseline in QoL "Vitality" at Week 24
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire, specifically SF-36 vitality score at week 24. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in vitality.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Units on a scale]	4.3 (19.73)	5.6 (17.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OROS Hydromorphone HCl, Oxycodone
	Comments	Exploratory comparison
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.543
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.94
	Confidence Interval	() 95%; -3.98 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference calculated: hydromorphone minus oxycodone

67. Secondary Outcome

Title	Change From Baseline in QoL at Week 52
Description	Change from baseline in QoL was assessed using the SF-36 QoL questionnaire at week 52. Scores could range from 0 to 100 with a high score indicating a better QoL. Positive change from baseline scores indicate improvement in QoL.
Time Frame	baseline and week 52

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
SF-36 bodily pain index	23.1 (22.07)	19.6 (22.67)
SF-36 general health perceptions	9.6 (17.86)	5.5 (18.97)
SF-36 health transition	-0.3 (0.90)	-0.1 (1.03)
SF-36 mental health	11.7 (17.21)	6.9 (26.03)
SF-36 physical functioning	11.4 (20.10)	9.2 (20.12)
SF-36 role emotional	22.1 (48.86)	7.3 (56.86)
SF-36 role physical	17.0 (38.02)	15.0 (33.50)
SF-36 social functioning	15.4 (23.11)	12.8 (28.29)
SF-36 vitality	11.5 (17.39)	11.9 (21.40)

68. Secondary Outcome

Title	Clinical Global Assessment of Efficacy
Description	Overall clinical efficacy was assessed by the Investigator using the following global ratings: very good, good, moderate, poor, or very poor, at weeks 4, 24, and 52.
Time Frame	weeks 4, 24, and 52

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Visit 5, week 4: very good	49	27
Visit 5, week 4: good	92	92
Visit 5, week 4: moderate	51	50
Visit 5, week 4: poor	12	9
Visit 5, week 4: very poor	0	3
Visit 8, week 24: very good	48	31
Visit 8, week 24: good	91	103
Visit 8, week 24: moderate	50	41
Visit 8, week 24: poor	44	50
Visit 8, week 24: very poor	16	10
Visit 10, week 52: very good	18	11
Visit 10, week 52: good	37	34
Visit 10, week 52: moderate	5	6
Visit 10, week 52: poor	0	1
Visit 10, week 52: very poor	0	0

69. Secondary Outcome

Title	Change in Dose of Study Treatment
Description	Number of subjects with change in dose of study treatment was assessed at weeks 4, 24, and 52.
Time Frame	weeks 4, 24, and 52

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
0 mg (week 4)	79	84
+8 mg (week 4)	102	0
+20 mg (week 4)	0	108
+24 mg (week 4)	73	0
+60 mg (week 4)	0	58
-60 mg (week 24)	0	2
-40 mg (week 24)	0	8
-24 mg (week 24)	1	0
-20 mg (week 24)	0	6
-16 mg (week 24)	4	0
-8 mg (week 24)	11	0
0 mg (week 24)	172	144
+8 mg (week 24)	6	0
+16 mg (week 24)	9	0
+20 mg (week 24)	0	8
+40 mg (week 24)	0	14
-16 mg (week 52)	3	0
-8 mg (week 52)	1	0
0 mg (week 52)	56	50
+40 mg (week 52)	0	2

70. Secondary Outcome

Title	Change in Dose of Study Treatment During Titration Phase (First 4 Weeks of Study) and Overall Treatment Phase I (First 24 Weeks of Study)
Description	Number of subejcts with change in dose of study treatment was assessed and stratified by time on study, at least 4 weeks versus dropped out at highest dose before week 4, at weeks 4 and 24.
Time Frame	weeks 4 and 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Titration phase (on study at least 4 weeks) 0 mg	50	41
Titration phase (on study at least 4 weeks) +8 mg	92	0
Titration phase (on study at least 4 weeks) +20 mg	0	94
Titration phase (on study at least 4 weeks) +24 mg	65	0
Titration phase (on study at least 4 weeks) +60 mg	0	54
Titration phase (on study <4 weeks) 0 mg	29	43
Titration phase (on study <4 weeks) +8 mg	10	0
Titration phase (on study <4 weeks) +20 mg	0	14
Titration phase (on study <4 weeks) +24 mg	8	0
Titration phase (on study <4 weeks) +60 mg	0	4
Week 24 (on study at least 4 weeks) 0 mg	58	40
Week 24 (on study at least 4 weeks ) +4 mg	0	1
Week 24 (on study at least 4 weeks ) +8 mg	76	0
Week 24 (on study at least 4 weeks) +20 mg	0	87
Week 24 (on study at least 4 weeks ) +24 mg	73	0
Week 24 (on study at least 4 weeks) +60 mg	0	61
Week 24 (on study <4 weeks) 0 mg	29	43
Week 24 (on study <4 weeks) +8 mg	10	0
Week 24 (on study <4 weeks) +20 mg	0	14
Week 24 (on study <4 weeks) +24 mg	8	0
Week 24 (on study <4 weeks) +60 mg	0	4

71. Secondary Outcome

Title	Number of Drop-outs
Description	Number of drop-outs according to reasons for drop-out and due to inefficacy at maximal dosage was assessed at weeks 24 and 52.
Time Frame	baseline to week 24 (core); week 24 to week 52 (extension)

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Adverse events (core)	57	56
Adverse events (extension)	4	1
Consent withdrawn (core)	12	16
Consent withdrawn (extension)	0	1
Inadequate pain relief (core)	22	18
Inadequate pain relief (extension)	0	1
Investigator withdrew patient (core)	4	2
Investigator withdrew patient (extension)	0	0
Lost to follow up (core)	2	0
Lost to follow up (extension)	1	0
Non compliance (core)	3	10
Non compliance (extension)	1	0
Other (core)	6	5
Other (extension)	4	2
Protocol violation (core)	6	6
Protocol violation (extension)	0	0
Treatment completed no follow up visit (core)	2	0
Treatment completed no follow up visit (extension)	0	0
Inefficacy at maximal dosage (core)	17	12

72. Secondary Outcome

Title	Number of Days With add-on Pain Medication
Description	Number of days with add-on pain medication during the first 24 weeks of the study was assessed at week 24.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Days]	68.2 (59.6)	66.1 (61.2)

73. Secondary Outcome

Title	Amount of add-on Pain Medication
Description	Total amount of add-on pain medication (paracetamol) for the first 24 weeks was assessed at week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [mg]	80004.8 (97004.53)	76191.9 (96925.72)

74. Secondary Outcome

Title	Mode and Convenience of Drug Intake.
Description	Subjects filled out a questionnaire based on the mode and convenience of drug intake and could rate their responses as very convenient, convenient, neither convenient or inconvenient, inconvenient, and very inconvenient.
Time Frame	weeks 4, 24, and 52

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Very convenient, week 4	57 (0.86)	36 (0.77)
Convenient, week 4	97 (0.96)	94 (1.01)
Neither convenient or inconvenient, week 4	30 (0.61)	30 (0.61)
Inconvenient, week 4	7	6
Very inconvenient, week 4	3	1
Very convenient, week 24	63	53
Convenient, week 24	96	90
Neither convenient or inconvenient, week 24	31	33
Inconvenient, week 24	8	11
Very inconvenient, week 24	7	8
Very convenient, week 52	21	11
Convenient, week 52	10	15
Neither convenient or inconvenient, week 52	2	2
Inconvenient, week 52	0	0
Very inconvenient, week 52	0	0

75. Secondary Outcome

Title	Resource Utilization of Pain Management
Description	Resource utilization was defined as the number of additional visits including additional telephone visits during the treatment period. This was assessed at week 24.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [Additional visits]	2.1 (2.21)	1.9 (2.29)

76. Primary Outcome

Title	Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (PP Population)
Description	If non-inferiority of OROS hydromorphone was established, the daily dose of OROS hydromorphone and SR oxycodone that induced the same pain control was to be calculated (average dose used at week 24). Relative equi-analgesic dose was defined as mean dose/allowed maximum dose*100. Allowed maximum doses were 32mg OROS hydromorphone and 80mg SR oxycodone respectively.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

PP population (all subjects who took the study medication at least once, who had post-baseline efficacy data, and who were without major protocol violation)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	115	108
Mean (Standard Deviation) [mg per day]	18.9 (9.44)	48.3 (22.4)

77. Primary Outcome

Title	Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (ITT Population)
Description	If non-inferiority of OROS hydromorphone was established, the daily dose of OROS hydromorphone and SR oxycodone that induced the same pain control was to be calculated (average dose used at week 24). Relative equi-analgesic dose was defined as mean dose/allowed maximum dose*100. Allowed maximum doses were 32mg OROS hydromorphone and 80mg SR oxycodone respectively.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [mg per day]	18.4 (9.92)	43.8 (23.12)

78. Primary Outcome

Title	Equi-analgesic Dose at Steady-state (PP Population)
Description	Dose of OROS hydromorphone and SR oxycodone that induced the same pain control at steady state, defined as the mean dose from week 4 to week 24.
Time Frame	week 4 to week 24

Outcome Measure Data

Analysis Population Description

PP population (all subjects who took the study medication at least once, who had post-baseline efficacy data, and who were without major protocol violation)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	115	108
Mean (Standard Deviation) [mg per day]	18.95 (9.223)	47.82 (21.663)

79. Primary Outcome

Title	Equi-analgesic Dose at Steady State (ITT Population)
Description	Dose of OROS hydromorphone and SR oxycodone that induced the same pain control at steady state, defined as the mean dose from week 4 to week 24.
Time Frame	week 4 to week 24

Outcome Measure Data

Analysis Population Description

ITT population (all randomized subjects who took the study medication at least once, excluding subjects who had no post-baseline efficacy data)

Arm/Group Title	OROS Hydromorphone HCl	Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)	Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
Measure Participants	254	250
Mean (Standard Deviation) [mg per day]	19.50 (9.584)	48.41 (21.835)

Adverse Events

Arm/Group Title	OROS Hydromorphone HCl		Oxycodone
Arm/Group Description	Initial dose 8 mg (minimum dose), 16 mg, or 32 mg (maximum dose), oral administration, once-daily, 4 weeks (titration phase), 20 weeks (maintenance phase), 28 weeks (extension phase)		Initial dose 10 mg (minimum dose), 20 mg, and 40 mg, oral administration, twice daily, 4 weeks (titration phase), 20 weeks (maintenance phase), and 28 weeks (extension phase)
All Cause Mortality
	OROS Hydromorphone HCl		Oxycodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	OROS Hydromorphone HCl		Oxycodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/254 (9.8%)		21/250 (8.4%)
Cardiac disorders
Angina unstable	1/254 (0.4%)	1	0/250 (0%)	0
Atrial fibrillation	2/254 (0.8%)	2	1/250 (0.4%)	1
Mitral valve incompetence	1/254 (0.4%)	1	0/250 (0%)	0
Myocardial infarction	0/254 (0%)	0	1/250 (0.4%)	1
Ear and labyrinth disorders
Vertigo	2/254 (0.8%)	2	2/250 (0.8%)	2
Gastrointestinal disorders
Abdominal pain upper	0/254 (0%)	0	1/250 (0.4%)	1
Colonic stenosis	1/254 (0.4%)	1	0/250 (0%)	0
Constipation	1/254 (0.4%)	1	0/250 (0%)	0
Gastric ulcer	1/254 (0.4%)	1	0/250 (0%)	0
Gastritis haemorrhagic	0/254 (0%)	0	1/250 (0.4%)	1
Gastrointestinal disorder	1/254 (0.4%)	1	0/250 (0%)	0
Ileus	0/254 (0%)	0	1/250 (0.4%)	1
Inguinal hernia	0/254 (0%)	0	1/250 (0.4%)	1
Mechanical ileus	1/254 (0.4%)	1	0/250 (0%)	0
Nausea	0/254 (0%)	0	1/250 (0.4%)	1
Peritonitis	0/254 (0%)	0	1/250 (0.4%)	1
Rectocele	0/254 (0%)	0	1/250 (0.4%)	1
Reflux oesophagitis	1/254 (0.4%)	1	0/250 (0%)	0
General disorders
Asthenia	0/254 (0%)	0	1/250 (0.4%)	1
Chest pain	0/254 (0%)	0	1/250 (0.4%)	1
Condition aggravated	1/254 (0.4%)	1	0/250 (0%)	0
Drug withdrawal syndrome	1/254 (0.4%)	1	0/250 (0%)	0
Fatigue	1/254 (0.4%)	1	0/250 (0%)	0
Withdrawal syndrome	0/254 (0%)	0	1/250 (0.4%)	1
Hepatobiliary disorders
Cholecystitis	0/254 (0%)	0	1/250 (0.4%)	1
Infections and infestations
Herpes zoster	0/254 (0%)	0	1/250 (0.4%)	1
Paronychia	0/254 (0%)	0	1/250 (0.4%)	1
Pneumonia	0/254 (0%)	0	1/250 (0.4%)	1
Sinusitis	0/254 (0%)	0	1/250 (0.4%)	1
Injury, poisoning and procedural complications
Contusion	0/254 (0%)	0	1/250 (0.4%)	1
Multiple fractures	0/254 (0%)	0	1/250 (0.4%)	1
Overdose	1/254 (0.4%)	1	0/250 (0%)	0
Post procedural complication	1/254 (0.4%)	1	0/250 (0%)	0
Postoperative fever	1/254 (0.4%)	1	0/250 (0%)	0
Investigations
Biopsy liver	1/254 (0.4%)	1	0/250 (0%)	0
Metabolism and nutrition disorders
Hypercholesterolaemia	0/254 (0%)	0	1/250 (0.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/254 (0.4%)	1	0/250 (0%)	0
Intervertebral disc protrusion	1/254 (0.4%)	1	0/250 (0%)	0
Osteoarthritis	1/254 (0.4%)	1	2/250 (0.8%)	2
Spondyloarthropathy	0/254 (0%)	0	1/250 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	1/254 (0.4%)	1	0/250 (0%)	0
Nervous system disorders
Cerebral ischaemia	0/254 (0%)	0	1/250 (0.4%)	1
Cerebrovascular accident	0/254 (0%)	0	1/250 (0.4%)	1
Neuralgia	0/254 (0%)	0	1/250 (0.4%)	1
Parkinson's disease	1/254 (0.4%)	1	0/250 (0%)	0
Sedation	1/254 (0.4%)	1	0/250 (0%)	0
Somnolence	1/254 (0.4%)	1	1/250 (0.4%)	1
Syncope	0/254 (0%)	0	1/250 (0.4%)	1
Vertebrobasilar insufficiency	1/254 (0.4%)	1	0/250 (0%)	0
Renal and urinary disorders
Renal impairment	0/254 (0%)	0	1/250 (0.4%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/254 (0%)	0	1/250 (0.4%)	1
Menorrhagia	1/254 (0.4%)	1	0/250 (0%)	0
Dyspnoea	1/254 (0.4%)	1	0/250 (0%)	0
Surgical and medical procedures
Angioplasty	0/254 (0%)	0	1/250 (0.4%)	1
Hip arthroplasty	1/254 (0.4%)	1	0/250 (0%)	0
Inguinal hernia repair	1/254 (0.4%)	1	0/250 (0%)	0
Knee arthroplasty	1/254 (0.4%)	1	0/250 (0%)	0
Pain management	0/254 (0%)	0	1/250 (0.4%)	1
Prosthesis implantation	1/254 (0.4%)	1	0/250 (0%)	0
Rehabilitation therapy	1/254 (0.4%)	1	0/250 (0%)	0
Spinal operation	1/254 (0.4%)	1	0/250 (0%)	0
Umbilical hernia repair	1/254 (0.4%)	1	0/250 (0%)	0
Vascular disorders
Hypotension	0/254 (0%)	0	1/250 (0.4%)	1
Other (Not Including Serious) Adverse Events
	OROS Hydromorphone HCl		Oxycodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	206/254 (81.1%)		212/250 (84.8%)
Ear and labyrinth disorders
Vertigo	14/254 (5.5%)	14	16/250 (6.4%)	17
Gastrointestinal disorders
Constipation	73/254 (28.7%)	92	65/250 (26%)	76
Diarrhoea	33/254 (13%)	45	14/250 (5.6%)	15
Nausea	68/254 (26.8%)	82	78/250 (31.2%)	92
Vomiting	32/254 (12.6%)	38	36/250 (14.4%)	43
General disorders
Fatigue	35/254 (13.8%)	37	31/250 (12.4%)	33
Metabolism and nutrition disorders
Anorexia	14/254 (5.5%)	16	13/250 (5.2%)	13
Nervous system disorders
Dizziness	17/254 (6.7%)	18	26/250 (10.4%)	30
Headache	22/254 (8.7%)	26	25/250 (10%)	32
Somnolence	9/254 (3.5%)	10	18/250 (7.2%)	23
Psychiatric disorders
Insomnia	13/254 (5.1%)	13	15/250 (6%)	17
Skin and subcutaneous tissue disorders
Hyperhidrosis	29/254 (11.4%)	35	22/250 (8.8%)	22
Pruritis	25/254 (9.8%)	27	26/250 (10.4%)	28

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.