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.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 504
- 主要终点
- Change From Baseline in Brief Pain Inventory (BPI) Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Per Protocol [PP] Population)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Oxycodone
干预措施: Oxycodone (Drug)
OROS hydromorphone HCl
干预措施: OROS hydromorphone HCl (Drug)
结局指标
主要结局
Change From Baseline in Brief Pain Inventory (BPI) Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Per Protocol [PP] Population)
时间窗: 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".
Change From Baseline in BPI Questionnaire Item 6 "Pain Right Now" Score at Week 24 (Intent to Treat [ITT] Population)
时间窗: 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".
Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (PP Population)
时间窗: 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.
Equi-analgesic Dose at Steady State (ITT Population)
时间窗: 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.
Equi-analgesic Dosage of OROS Hydromorphone Once-daily and SR Oxycodone Twice-daily (ITT Population)
时间窗: 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.
Equi-analgesic Dose at Steady-state (PP Population)
时间窗: 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.
次要结局
- Change From Baseline in Sleep Quality at Week 24(baseline and week 24)
- Change From Baseline in Subject Diary Evening Mean Pain Score "Pain Right Now" at Week 24(baseline and week 24)
- Change From Baseline in Subject Diary Morning Mean Pain Score "Pain Right Now" at Week 24(baseline and week 24)
- Number of Subjects With Dose Escalation(week 4 and week 24)
- 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 BPI Pain Severity "Pain at Its Worst" (BPI Item 3) at Week 4(baseline and week 4)
- Change From Baseline in BPI Pain Severity "Average Pain" (BPI Item 5) at Week 4(baseline and week 4)
- Change From Baseline in BPI Severity Score "Pain Right Now" (BPI Item 6) at Week 4(baseline and week 4)
- Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 4(baseline and week 4)
- 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 BPI Pain Severity "Average Pain" (BPI Item 5) at Week 24(baseline and week 24)
- Change From Baseline in BPI Pain Relief Score (BPI Item 8) at Week 24(baseline and week 24)
- Change From Baseline in BPI Pain Severity Score (Mean of BPI Items 3 to 6) at Week 24(baseline and week 24)
- 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)
- Number of Subjects Indicating That They Had Optimal Sleep at Week 24(baseline and week 24)
- 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 Interference Score "Interfered With General Activity" (BPI Item 9a) at Week 4(baseline and week 4)
- 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 "Pain Interfered With Walking Ability" (BPI Item 9c) at Week 4(baseline and week 4)
- 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 "Pain Interfered With Relations With Other People" (BPI Item 9e) at Week 4(baseline and week 4)
- 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 "Pain Interfered With Enjoyment of Life" (BPI Item 9g) at Week 4(baseline and week 4)
- 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 "Pain Interfered With Mood" (BPI Item 9b) at Week 24(baseline and week 24)
- 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 "Pain Interfered With Normal Work" (BPI Item 9d) at Week 24(baseline and week 24)
- Change From Baseline in QoL "Social Functioning" at Week 4(baseline and week 4)
- 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 "Pain Interfered With Sleep" (BPI Item 9f) at Week 24(baseline and week 24)
- 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 BPI Pain Severity, Relief and Interference Scores (Extension Phase)(baseline and week 52)
- Change From Baseline in Sleep Quality (MOS Index I) at Week 4(baseline and week 4)
- Change From Baseline in Sleep Quality (MOS Index II) at Week 4(baseline and week 4)
- Change From Baseline in Sleep Quality (MOS Index II) at Week 24(baseline and week 24)
- Change From Baseline in Sleep Quality, Sleep Disturbance at Week 24(baseline and week 24)
- Change From Baseline in Sleep Quality, Snoring at Week 24(baseline and week 24)
- 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 Adequacy at Week 24(baseline and week 24)
- Change From Baseline in Sleep Quality, Sleep Somnolence at Week 24(baseline and week 24)
- Change From Baseline in Sleep Quality, Sleep Quantity at Week 24(baseline and week 24)
- Change From Baseline in Sleep Quality at Week 52(baseline and week 52)
- Number of Subjects Indicating Optimal Sleep at Week 52(week 52)
- Change From Baseline in Subject Diary Mean Pain Evening, Morning, and All Day Scores at Week 24(baseline and week 24)
- 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)
- Number of Subjects With Dose Escalation at Week 4 (ITT Population)(week 4)
- Number of Subjects With Dose Escalation at Week 24 (ITT Population)(week 24)
- Change From Baseline in Quality of Life (QoL) "Bodily Pain" at Week 4(baseline and week 4)
- Change From Baseline in QoL "General Health Perceptions" at Week 4(baseline and week 4)
- Change From Baseline in QoL "Health Transition" at Week 4(baseline and week 4)
- Change From Baseline in QoL "Mental Health" at Week 4(baseline and week 4)
- Change From Baseline in QoL "Physical Functioning" at Week 4(baseline and week 4)
- Change From Baseline in QoL "Role Emotional" at Week 4(baseline and week 4)
- Change From Baseline in QoL "Role Physical" at Week 4(baseline and week 4)
- Change From Baseline in QoL "Vitality" at Week 4(baseline and week 4)
- Change From Baseline in QoL "Bodily Pain" at Week 24(baseline and week 24)
- Change From Baseline in QoL "General Health Perceptions" at Week 24(baseline and week 24)
- Change From Baseline in QoL "Health Transition" at Week 24(baseline and week 24)
- Change From Baseline in QoL "Mental Health" at Week 24(baseline and week 24)
- Change From Baseline in QoL "Physical Functioning" at Week 24(baseline and week 24)
- Change From Baseline in QoL "Role Emotional" at Week 24(baseline and week 24)
- Change From Baseline in QoL "Role Physical" at Week 24(baseline and week 24)
- Change From Baseline in QoL "Social Functioning" at Week 24(baseline and week 24)
- Change From Baseline in QoL "Vitality" at Week 24(baseline and week 24)
- Change From Baseline in QoL at Week 52(baseline and week 52)
- Clinical Global Assessment of Efficacy(weeks 4, 24, and 52)
- 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)
- Change in Dose of Study Treatment(weeks 4, 24, and 52)
- Number of Drop-outs(baseline to week 24 (core); week 24 to week 52 (extension))
- Number of Days With add-on Pain Medication(week 24)
- Amount of add-on Pain Medication(24 weeks)
- Mode and Convenience of Drug Intake.(weeks 4, 24, and 52)
- Resource Utilization of Pain Management(week 24)