Evaluation of Efficacy and Safety of VX-548 for Acute Pain After a Bunionectomy

A Phase 3, Randomized, Double-blind, Placebo-controlled 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 suzetrigine for acute pain after a bunionectomy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1075
• Phase: Phase 3

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
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Bakersfield, California, United States, 93301
      • Trovare Clinical Research
    • San Diego, California, United States, 92103
      • Pacific Research Network Inc
    • Tarzana, California, United States, 91356
      • New Hope Research Development
    • West Covina, California, United States, 91790
      • New Hope Research Development
  • Florida
    • Hialeah, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Tampa, Florida, United States, 33613
      • ForCare Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Kansas Spine and Specialty Hospital
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
  • Oklahoma
    • Jenks, Oklahoma, United States, 74037
      • Center for Orthopaedic Reconstruction and Excellence
  • Texas
    • Bellaire, Texas, United States, 77401
      • HD Research LLC | First Surgical Hospital
    • Carrollton, Texas, United States, 75006
      • HD Research LLC | Legent Orthopedic Hospital
    • Houston, Texas, United States, 77008
      • HD Research LLC | Houston Heights Hospital
    • McAllen, Texas, United States, 78501
      • Futuro Clinical Trials
    • San Antonio, Texas, United States, 78240
      • Endeavor Clinical Trials
    • Webster, Texas, United States, 77598
      • Houston Physicians Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Before Surgery

  • Participants 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 or other foot surgery on the index foot; or bunionectomy on the opposite foot
  • History of cardiac dysrhythmias within the last 2 years requiring anti-arrhythmia treatment(s)
  • Any prior surgery within 1 month before the first study drug dose

• After Surgery

  • Participant had a type 3 deformity requiring a base wedge osteotomy, concomitant surgery such as hammertoe repair; or experienced medical complications during the bunionectomy
  • Participant had a medical complication 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: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to suzetrigine (SUZ) 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 SUZ); Placebo matched to SUZ for oral administration.
Active Comparator: Hydrocodone bitartrate/acetaminophen (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.; Drug: Placebo (matched to SUZ); Placebo matched to SUZ for oral administration.
Experimental: Suzetrigine (SUZ); Participants received SUZ [100 mg as first dose, followed by 50 mg every 12 hours (q12h)] for 2 days.	Drug: Placebo (matched to HB/APAP); Placebo matched to HB/APAP for oral administration.; Drug: SUZ; Tablets for oral administration.; Other Names: VX-548

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48), SUZ Compared to Placebo	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 subtracting the baseline pain intensity score from the pain intensity score at each postdose time point (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
Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo		0 to 48 Hours After First Dose of Study Drug
Total Rescue Medication Usage, SUZ Compared to Placebo		0 to 48 Hours After First Dose of Study Drug
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Day 1 up to Day 19
Time-weighted Sum of the Pain Intensity Difference (SPID) as Recorded on a Numeric Pain Rating Scale (NPRS) From 0 to 48 Hours (SPID48), SUZ Compared to HB/APAP	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 baseline pain intensity score from the pain intensity score at each post dose time point(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
Time to Greater Than or Equal to (≥)2-Point Reduction in NPRS,SUZ Compared to Placebo	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The time to ≥ 2-point reduction in NPRS from baseline was the time elapsed from the first dose of study drug until the first time the participant had at least a 2-point reduction in NPRS scores from baseline.	From Baseline Up to 48 Hours After First Dose of Study Drug
Time to ≥1-Point Reduction in NPRS, SUZ Compared to Placebo	Pain intensity was recorded on 11-point NPRS, score range: 0 to 10, where 0= no pain and 10= worst imaginable pain. The time to ≥1-point reduction in NPRS from baseline was the time elapsed from the first dose of study drug until the first time the participant had at least a 1-point reduction in NPRS from baseline.	From Baseline Up to 48 Hours After First Dose of Study Drug
Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo	The PGA is a single-item assessment of patient perceptions of the method of pain control with the study drug and is evaluated on a 4-point Likert scale as: (poor, fair, good, or excellent). Percentage of participants who reported good or excellent on the PGA scale were reported.	At 48 Hours After First Dose of Study Drug
Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP	The percentage of participants with the events of vomiting or nausea during the specified time frame was reported.	From Baseline up to Day 19
Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo	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 baseline pain intensity score from the pain intensity score at each post dose time point (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
Time to First Use of Rescue Medication, SUZ Compared to Placebo	Time to first use of rescue medication is the time from the first dose of study drug until the first use of rescue medication.	0 to 48 Hours After First Dose of Study Drug

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 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: VX22-548-104

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