A Phase 2, Double-blind, Randomized, Placebo-controlled, Four-arm, Multicenter, Dose-finding Study to Assess the Safety and Efficacy of Three Dose Levels of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Central Neuropathic Pain in Patients With Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 209
- 试验地点
- 71
- 主要终点
- Association Between the Dextromethorphan Plasma Concentration and the Change From Baseline Pain Rating Scale (PRS) Score to the Average Pain Rating Scale Score During Days 57 Through 84
研究概览
简要总结
The objectives of the study are to evaluate the safety, tolerability, and efficacy of 3 doses of AVP-923 capsules in the treatment of central neuropathic pain in participants with multiple sclerosis.
详细描述
The objectives of the study are to evaluate the safety, tolerability, and efficacy of 3 doses of AVP-923 (dextromethorphan [DM]/quinidine [Q]) capsules containing either 45 mg DM and 10 mg Q (AVP-923-45) or 30 mg DM and 10 mg Q (AVP-923-30) or 20 mg DM and 10 mg Q (AVP-923-20) compared to placebo, for the treatment of central neuropathic pain in a population of participants with multiple sclerosis (MS) over a 12-week period. The MS participant population enrolled includes participants with relapsing-remitting multiple sclerosis (RRMS) and participants with secondary progressive multiple sclerosis (SPMS).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Multiple Sclerosis (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS]), Clinical history and symptoms of central neuropathic pain (dysesthetic pain) for at least 3 months prior to screening, pain rating scale (PRS) baseline score = or > 4, No MS relapse within previous 30 days.
排除标准
- •Personal history of complete heart block, QT interval corrected for heart rate (QTc) prolongation, or torsades de pointes, family history of congenital QT interval prolongation syndrome, Myasthenia Gravis, Beck Depression Inventory Second Edition (BDI-II) score > 19
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
AVP-923-45
干预措施: AVP-923-45 (Drug)
AVP-923-30
干预措施: AVP-923-30 (Drug)
AVP-923-20
干预措施: AVP-923-20 (Drug)
结局指标
主要结局
Association Between the Dextromethorphan Plasma Concentration and the Change From Baseline Pain Rating Scale (PRS) Score to the Average Pain Rating Scale Score During Days 57 Through 84
时间窗: Baseline; Days 57 through 84 (PRS score); Days 22 and 50 (dextromethorphan plasma concentrations)
PRS required participants to rate their pain over the past 12 hours (hrs) on a scale of 0 to 10 (0=no pain; 10=worst possible pain). Baseline (B) PRS was defined as the average of the PRS scores in the last 7 days collected prior to the B visit. If participants did not have at least 4 PRS scores during the last 7 days prior to the B visit, then the average of up to 7 of the most recent PRS scores available prior to the B visit was used. Post-B PRS was the average of Days 57 through 84 values. For participants who did not have any PRS scores during Days 57 through 84, the average of the last 7 available post-B PRS scores was used. Change from B was calculated as the post-B score minus B score. The average logarithms of dextromethorphan plasma concentrations (Cmax) on Days 22 and 50 are reported in primary outcome measure #2 below. Pearson correlation was calculated between Cmax as one group of data across the reporting groups and Change from Baseline in PRS score.
Average Logarithms of Dextromethorphan (DM) Plasma Concentrations (Cmax) on Days 22 and 50
时间窗: 0 to 3 hours post-dose on Day 22 and 50
The average of the logarithms of the DM plasma concentrations on Days 22 and 50 were presented.
次要结局
- Mean Change From Baseline in Fatigue Severity Scale (FSS) Scores at Days 57 Through 84(Baseline; Days 57 through 84)
- Mean Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Scores at Day 85(Baseline; Day 85)
- Comparison of the Adjusted Mean Change From Baseline PRS Score to the Average PRS Score During Days 57 Through 84(Baseline; Days 57 through 84)
- Mean Change From Baseline in Expanded Disability Status Scale (EDSS) Scores at Days 22 and 85(Baseline; Days 22 and 85)
- Mean Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Scores at Day 85(Baseline; Day 85)
- Mean Change From Baseline in MS Neuropsychological Screening Questionnaire (MSNQ) Scores at Day 85(Baseline; Day 85)
- Mean Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores at Day 85(Baseline; Day 85)
- Mean Change From Baseline in Beck Depression Inventory (BDI-II) Scores at Day 85(Baseline; Day 85)
- Mean Overall Patient Global Impression of Change (PGIC) Scores at Day 85(Day 85)
- Mean Numerical Rating Scale (NRS) Scores at Days 22, 50, and 85(Days 22, 50, and 85)