A Study Evaluating Efficacy and Safety of VX-548 for Acute Pain After a Bunionectomy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of VX-548 doses in treating acute pain after a bunionectomy.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Study Evaluating the Efficacy and Safety of VX-548 for Acute Pain After a Bunionectomy

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: VX-548
* Drug: HB/APAP
* Drug: Placebo (matched to VX-548)
* Drug: Placebo (matched to HB/APAP)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Before Surgery: Participant scheduled to undergo a primary unilateral bunionectomy with distal first metatarsal osteotomy (i.e., Austin procedure) and internal fixation under regional anesthesia (Mayo and popliteal sciatic block) After Surgery: Participant is lucid and able to follow commands All analgesic guidelines were followed during and after the bunionectomy Key Exclusion Criteria: Before Surgery: Prior history of bunionectomy or other foot surgery on the index foot History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s) Any prior surgery within 1 month before the first study drug After Surgery: Participant had a Type 3 deformity requiring a base wedge osteotomy or concomitant surgery such as hammertoe repair, or had medical complications during the bunionectomy that, in the opinion of the investigator, should preclude randomization Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VX-548<br>Participants will be randomized to receive different dose levels of VX-548. | Drug: VX-548<br>* Tablets for oral administration.<br>Drug: Placebo (matched to HB/APAP)<br>* Placebo matched to HB/APAP for oral administration.<br>|
| Active Comparator: Hydrocodone bitartrate/acetaminophen (HB/APAP)<br>Participants will receive HB/APAP. | Drug: HB/APAP<br>* Capsules for oral administration.<br>Drug: Placebo (matched to VX-548)<br>* Placebo matched to VX-548 for oral administration.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebos matched to VX-548 and HB/APAP. | Drug: Placebo (matched to VX-548)<br>* Placebo matched to VX-548 for oral administration.<br>Drug: Placebo (matched to HB/APAP)<br>* Placebo matched to HB/APAP for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted sum of Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 48 Hours (SPID48) After the First Dose of Study Drug |  | 0 to 48 Hours After the First Dose of Study Drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) After the First Dose of Study Drug |  | 0 to 24 Hours After the First Dose of Study Drug | 
| Proportions of Participants With >=30 Percent (%), >=50%, and >=70% Reduction in NPRS at 48 Hours After the First Dose of Study Drug |  | At 48 Hours After the First Dose of Study Drug | 
| Maximum Observed Plasma Concentration (Cmax) of VX-548 |  | Pre-dose to 12 Hours and 24 to 36 Hours After the First Dose of Study Drug | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 |  | Pre-dose to 12 Hours and 24 to 36 Hours After the First Dose of Study Drug | 
| Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548 |  | Pre-dose to 12 Hours and 24 to 36 Hours After the First Dose of Study Drug | 
| Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Day 1 up to Day 18 |