A Phase 2B Randomized, Double-blind, Placebo-controlled, Dose-ranging, Parallel-design Study of the Efficacy and Safety of VX-150 for Acute Pain Following Bunionectomy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 250
- 试验地点
- 6
- 主要终点
- Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose
研究概览
简要总结
This study will evaluate the dose-response relationship and safety of VX-150 in treating acute pain following bunionectomy.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Before surgery:
- •Body mass index (BMI) of 18.0 to 38.0 kilogram per meter square (kg/m^2)
- •Be scheduled to undergo a primary unilateral first metatarsal bunionectomy repair, without collateral procedures, under regional anesthesia (Mayo and popliteal sciatic block) not to include base wedge procedure
- •After surgery:
- •Subject reported pain of greater than or equal to (>=) 4 on Numeric Pain Rating Scale (NPRS) and moderate or severe pain on the Verbal Categorical Rating Scale (VRS) within 9 hours after removal of the popliteal sciatic block on Day 1
- •Subject is lucid and able to follow commands
- •All analgesic guidelines were followed during and after the bunionectomy
排除标准
- •Before surgery:
- •History in the past 10 years of malignancy, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ
- •History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s)
- •History of abnormal laboratory results >=2.5*upper limit of normal (ULN)
- •History of peripheral neuropathy
- •A known or clinically suspected infection with human immunodeficiency virus or hepatitis B or C viruses
- •Prior medical history of bunionectomy or other foot surgery on the index foot
- •History of peptic ulcer disease, or intolerance or unwillingness to receive ibuprofen
- •After surgery:
- •Subject had a type 3 deformity requiring a base wedge osteotomy or concomitant surgery
- •Other protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Placebo
Participants received placebo matched to VX-150 for 2 days.
干预措施: Placebo (Drug)
VX-150 - Dose Level 1
Participants received VX-150 1500 milligrams (mg) as first dose, followed by VX-150 750 mg every 12 hours (q12h) for 2 days.
干预措施: VX-150 (Drug)
VX-150 - Dose Level 2
Participants received VX-150 1000 mg once daily (qd) for 2 days.
干预措施: VX-150 (Drug)
VX-150 - Dose Level 3
Participants received VX-150 500 mg q12h for 2 days.
干预措施: VX-150 (Drug)
VX-150 - Dose Level 4
Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.
干预措施: VX-150 (Drug)
VX-150 - Dose Level 5
Participants received VX-150 250 mg qd for 2 days.
干预措施: VX-150 (Drug)
结局指标
主要结局
Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose
时间窗: 0 to 24 Hours After First Dose
SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference was calculated by subtracting the pain intensity score at given post-dose time points from the baseline pain intensity scores (using pain rating score range: 0= no pain to 10= worst possible pain). SPID24 was calculated from 0 to 24 hours and the score range was -240 (worst score) to 240 (best score).
次要结局
- Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose(0 to 48 Hours After First Dose)
- Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo(From Baseline at 24 Hours After First Dose)
- Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo(From Baseline at 24 Hours After First Dose)
- Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo(From Baseline at 24 Hours After First Dose)
- Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo(Up to 6 hours After the First Dose)
- Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114(Day 1 and Day 2)
- Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Day 1 up to Day 10)
- Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo(Up to 6 Hours After the First Dose)
- Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5)(Day 1 and Day 2)