A Two-part, Placebo-controlled, Study of the Safety and Efficacy of Sativex® Oromucosal Spray (Sativex®; Nabiximols) as Adjunctive Therapy in Relieving Uncontrolled Persistent Chronic Pain in Patients With Advanced Cancer, Who Have Inadequate Analgesia Even With Optimized Chronic Opioid Therapy.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 406
- 主要终点
- Change From Randomization Baseline In Mean NRS Average Pain At End Of Treatment
研究概览
简要总结
The primary objective of this study was to evaluate the efficacy of nabiximols (Sativex®), compared with placebo, when used as an adjunctive measure in relieving uncontrolled persistent chronic pain (not breakthrough pain) in participants with advanced cancer, who had inadequate analgesia even with optimized chronic opioid therapy.
This multi-center study was conducted in two parts. All participants enrolled into the trial received nabiximols during one of two parts of the study, but they did not know which part.
Eligible participants were not required to stop any of their current treatments or medications.
详细描述
This 11-week, multi-center, placebo-controlled study aimed to determine the efficacy, safety and tolerability of nabiximols administered as an adjunctive treatment for 5 weeks, versus placebo, assessed by a 2-part, randomized withdrawal design. The first part of the study (Part A) was single-blind (participants) and the second part of the study (Part B) was randomized, double-blind. Eligible participants had advanced cancer, with a clinical diagnosis of cancer related pain which was not wholly alleviated by their current optimized opioid treatment.
Qualifying participants entered the study at screening and commenced a 5- to 14-day eligibility period. During this period, eligible participants had 3 consecutive days where pain severity remained within defined parameters, break-through opioid usage had not exceeded an average of 4 episodes per day, and maintenance opioid medication and dose had not changed. Eligible participants underwent nabiximols titration during a single-blind treatment period lasting 10 days, followed by 4 days of therapy at the titrated dose. Participants who demonstrated an improvement of 15% or more on the score of the pain numerical rating scale were advanced to Part B, where they were randomized 1:1 to nabiximols or placebo in a double-blind fashion. Participants then received study treatments at their self-titrated doses for 5 weeks. After the end of the 5-week treatment period, participants were offered the option of entering an open-label extension (OLE) study; participants who entered the OLE up to 7 days after study completion had their follow-up assessments performed on the same day as their first OLE study visit. Participants that did not enter the OLE study had a safety follow up visit 14 days after treatment completion, which could be via telephone.
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
- Triple (Participant, Care Provider, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Nabiximols
Nabiximols was self-administered by participants as a 100 microliter (μL) oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day for 2 or 7 weeks. Nabiximols oromucosal spray contained delta-9-tetrahydrocannabinol (THC) (27 milligrams [mg]/milliliter [mL]):cannabidiol (CBD) (25 mg/mL), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%)flavoring. Each 100 μL actuation delivered 2.7 mg THC and 2.5 mg CBD.
干预措施: Nabiximols (Drug)
Placebo (GA-0034)
Placebo was self-administered by participants as a 100 μL oromucosal spray in the morning and evening, up to a maximum of 10 sprays per day for 5 weeks. Placebo oromucosal spray contained ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavoring and colorings.
干预措施: Placebo (GA-0034) (Drug)
结局指标
主要结局
Change From Randomization Baseline In Mean NRS Average Pain At End Of Treatment
时间窗: Randomization Baseline, End of Treatment (Day 36 of the double-blind period)
Participants indicated the level of pain experienced in the last 24 hours on an 11-point NRS, where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine." Change in mean NRS average pain was calculated as: End of Treatment NRS average pain score - Randomization (Part B) Baseline NRS average pain score. The participant's Randomization (Part B) baseline pain 0-10 NRS value was the mean over the last 4 consecutive days of the single-blind treatment period (Part A; pre-randomization). A negative value indicates an improvement in average pain score from Randomization (Part B) Baseline.
次要结局
- Percent Improvement From Eligibility Baseline In Mean NRS Average Pain Score At End Of Treatment(Eligibility Baseline, End of Treatment (Day 36 of the double-blind period))
- Change From Randomization Baseline In Mean NRS Worst Pain At End Of Treatment(Randomization Baseline, End of Treatment (Day 36 of the double-blind period))
- Change From Randomization Baseline In Mean Sleep Disruption NRS At End Of Treatment(Randomization Baseline, End of Treatment (Day 36 of the double-blind period))
- Subject Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)(Last Visit (up to Day 36 of the double-blind period))
- Physician Global Impression Of Change At Last Visit (Up To Day 36 Of The Double-blind Period)(Last Visit (up to Day 36 of the double-blind period))
- Patient Satisfaction Questionnaire At Last Visit (Up To Day 36 Of The Double-blind Period)(Last Visit (up to Day 36 of the double-blind period))
- Change From Randomization Baseline In Daily Total Opioid Use (Morphine Equivalent) At End Of Treatment(Randomization Baseline, End of Treatment (Day 36 of the double-blind period))
- Change From Randomization Baseline In Daily Maintenance Opioid Dose (Morphine Equivalent) At End Of Treatment(Randomization Baseline, End of Treatment (Day 36 of the double-blind period))
- Change From Randomization Baseline In NRS Constipation At Last Visit (Up To Day 36 Of The Double-blind Period)(Randomization Baseline, Last Visit (up to Day 36 of the double-blind period))
- Change From Randomization Baseline In Daily Break-through Opioid Dose (Morphine Equivalent) At End Of Treatment(Randomization Baseline, End of Treatment (Day 36 of the double-blind period))