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

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

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

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: VX-548; Drug: Placebo (matched to HB/APAP); Drug: HB/APAP; Drug: Placebo (matched to VX-548)

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • Shoals Medical Trials Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research
    • Tarzana, California, United States, 91356
      • New Hope Research Development
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Chesapeake Research Group
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Texas
    • Bellaire, Texas, United States, 77401
      • First Surgical Hospital
    • Carrollton, Texas, United States, 75006
      • Legent Orthopedic Hospital
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VX-548: High Dose; Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.	Drug: VX-548; Tablets for oral administration.; Other Names: Suzetrigine
Placebo Comparator: Placebo; Participants received placebo matched to VX-548 and Hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days.	Drug: Placebo (matched to HB/APAP); Placebo matched to HB/APAP for oral administration.; Drug: Placebo (matched to VX-548); Placebo matched to VX-548 for oral administration.
Active Comparator: HB/APAP; Participants received HB 5 milligrams (mg)/ APAP 325 mg every 6 hours (q6h) for 2 days.	Drug: HB/APAP; Capsules for oral administration.
Experimental: VX-548: Low Dose; Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg tablet every 12 hours (q12h) for 2 days.	Drug: VX-548; Tablets for oral administration.; Other Names: Suzetrigine
Experimental: VX-548: Mid Dose; Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.	Drug: VX-548; Tablets for oral administration.; Other Names: Suzetrigine

What is the study measuring?

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	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). SPID48 was calculated from 0 to 48 hours and the score range was -480 (worst score) to 480 (best score).	0 to 48 hours After 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	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).	0 to 24 hours After First Dose of Study Drug
Percentage of Participants With at Least 30 Percent (%) Reduction in NPRS at 48 Hours After the First Dose of Study Drug	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The percentage of participants with at least 30% reduction from baseline in NPRS at 48 hours after the first dose of VX-548, HB/APAP or placebo was reported.	From Baseline at 48 Hours After First Dose of Study Drug
Percentage of Participants With at Least 50% Reduction in NPRS at 48 Hours After the First Dose of Study Drug	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The percentage of participants with at least 50% reduction from baseline in NPRS at 48 hours after the first dose of VX-548, HB/APAP or placebo were reported.	From Baseline at 48 Hours After First Dose of Study Drug
Percentage of Participants With at Least 70% Reduction in NPRS at 48 Hours After the First Dose of Study Drug	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The percentage of participants with at least 70% reduction from baseline in NPRS at 48 hours after the first dose of VX-548, HB/APAP or placebo were reported.	From Baseline at 48 Hours After First Dose of Study Drug
Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite)		Day 1 and Day 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite)		Day 1 and Day 2
Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VX-548 and M6-548 (Metabolite)		Day 1 and Day 2
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Day 16

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Actual): February 17, 2022
• Study Completion (Actual): March 4, 2022

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: July 15, 2021
• First Posted (Actual): July 26, 2021

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 9, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Acetaminophen
• Other Study ID Numbers: VX21-548-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No