A Randomized Double-blind, Placebo- and Active-control, Parallel-arm, Phase III Trial With Controlled Adjustment of Dose to Evaluate the Efficacy and Safety of CG5503 Prolonged Release (PR) in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 990
- 试验地点
- 100
- 主要终点
- Change From Baseline of the Average Pain Intensity Overall in the 12-week Maintenance Period of the Daily Pain Intensity on an 11-point Numeric Rating Scale (NRS).
研究概览
简要总结
The purpose of this study is to evaluate whether tapentadol (CG5503) prolonged-release (PR) tablets at doses of 100-250 mg twice daily provide a better pain relief in patients with moderate to severe chronic pain due to osteoarthritis of the knee than a placebo (a medication without active substance). In addition the tolerability of CG5503 PR will be assessed. One third of the patients will receive CG5503 and one third will receive placebo. For further comparison one third of the patients will receive oxycodone controlled release (CR) at doses of 20-50 mg twice daily which is an active approved pain medication. Please note that tapentadol ER (Extended Release) and tapentadol PR (Prolonged Release) are identical and used interchangeably. This is due to United States of America and European naming conventions.
详细描述
This is a randomized (study medication assigned to patients by chance), double-blind (neither patient nor investigator knows which patient gets which study medication, i.e. CG5503, placebo, oxycodone), placebo and active control study. The primary objective is to evaluate the efficacy and safety of orally administered tapentadol (CG5503) prolonged-release (PR) at doses of 100-250 mg (base) twice daily in patients with moderate to severe chronic pain from osteoarthritis (OA) of the knee. The study will consist of five periods: screening (to assess eligibility), washout (3-7 days with determination of a baseline pain intensity), titration (of dose over 3 weeks to the optimal individual level), maintenance (investigational drug intake for 12 weeks with adjustments allowed), and follow-up (2 weeks after end of treatment). The study hypothesis is that the study drug will be more effective than placebo in reducing patients' pain intensity. The secondary objectives include the collection of pharmacokinetic (related to how the body absorbs, distributes, changes and excretes the drug) information for dose verification. The efficacy objectives will be assessed by comparing the baseline pain level to the pain level during the maintenance period. This will be done by looking at the patients' pain diary information (electronic diaries).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with osteoarthritis of the knee based on the American College of Rheumatology (ACR) criteria and functional capacity class of I- III;
- •Patients taking analgesic medications for at least 3 months prior to screening and dissatisfied with their current therapy;
- •Patients requiring opioid treatment must be taking daily doses of opioid- based analgesic, equivalent to <160 mg of oral morphine;
- •Baseline score of >=5 on an 11-point numeric rating scale, calculated as the average pain intensity during the last 3 days prior to randomization.
排除标准
- •History of alcohol and/or drug abuse in Investigator's judgment;
- •Chronic hepatitis B or C, or HIV, presence of active hepatitis B or C within the past 3 months;
- •Life-long history of seizure disorder or epilepsy;
- •History of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated;
- •Uncontrolled hypertension;
- •Patients with severely impaired renal function;
- •Patients with moderate to severely impaired hepatic function or with laboratory values reflecting inadequate hepatic function,
- •Treatment with neuroleptics, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants, anticonvulsants, or anti-parkinsonian drugs, treatment with any other analgesic therapy than investigational medication or rescue medication during the trial.
研究组 & 干预措施
Matching Placebo (twice daily)
The starting dose of placebo was matched with the active treatment arms taken twice daily for the first 3 days. The dose was then increased to match the active treatments for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days as in the active treatment arms. Dose decreases were allowed without time restrictions.
干预措施: Matching Placebo (twice daily) (Drug)
Tapentadol ER (100 to 250 mg twice daily)
The starting dose was tapentadol ER 50 mg twice daily for 3 days. The dose was then increased to 100 mg tapentadol ER twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions.
干预措施: Tapentadol ER (100 to 250 mg twice daily) (Drug)
Oxycodone CR (20 to 50 mg twice daily)
The starting dose was oxycodone CR 10 mg twice daily for 3 days. The dose was then increased to 20 mg oxycodone CR twice daily for at least 4 days. Thereafter, during the titration and maintenance phase participants were allowed to increase the dose every 3 days. Dose decreases were allowed without time restrictions.
干预措施: Oxycodone CR (20 to 50 mg twice daily) (Drug)
结局指标
主要结局
Change From Baseline of the Average Pain Intensity Overall in the 12-week Maintenance Period of the Daily Pain Intensity on an 11-point Numeric Rating Scale (NRS).
时间窗: Change from baseline over the 12 week Maintenance Period
For this twice daily pain assessment, the participants were required to indicate the level of pain experienced over the previous 12 hours on an 11-point Numeric Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The lower the value the less pain in the treatment group. Negative values indicate a reduction in pain.
次要结局
- Time to Treatment Discontinuation Due to Lack of Efficacy(Baseline to week 12 of the maintenance period)
- Patient Global Impression of Change(Baseline; End of 12 week maintenance period)
- Change in the Health Survey Scores Form (SF-36)(Change From Baseline to Week 12 of the Maintenance Period)
- Sleep Questionnaire: Amount of Time Slept in Hours(Baseline to Week 12 of the maintenance period)
- Number of Participants Reporting a Category From the Quality of Sleep (Sleep Questionnaire)(Week 12 of the maintenance period compared to baseline)
- Sleep Questionnaire: Change From Baseline in Sleep Latency Time in Hours to the Last Week of the Maintenance Period.(Week 12 of the maintenance period compared to baseline)
- Sleep Questionnaire: Number of Awakenings During Sleep(Week 12 of the maintenance period compared with baseline)
- Change From Baseline of the Average Pain Intensity Based on an 11-point Numerical Rating Scale (NRS) Over the Last Week of the Maintenance Period at Week 12.(Change from Baseline to Week 12 of the Maintenance Period)
- Change From Baseline in the Western Ontario McMaster Questionnaire (WOMAC) Global Score Assessing Pain, Disability and Joint Stiffness of the Knee Over the Last Week of the Maintenance Period at Week 12(Change from baseline to week 12 of the maintenance period)
- EuroQol-5 (EQ-5D) Health Status Index Outcome Over Time(Comparison of Baseline to Week 12 of the Maintenance Period)
- Patient Assessment of Constipation Symptoms (PAC-SYM) Over Time(Change from Baseline to Week 12 of the Maintenance Period)