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

NCT04977336 | Completed Phase 2 Results FDA Drug

• 1 other identifier: VX21-548-101
• Study Type: interventional
• Target: 274
• Locations: 1 country
• Sites: 12

Brief Summary

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

Conditions

Acute Pain

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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 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

  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

  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

  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

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Participants received placebo matched to VX-548 and Hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days.

Drug: Placebo (matched to VX-548); Drug: Placebo (matched to HB/APAP)

HB/APAP

ACTIVE COMPARATOR

Participants received HB 5 milligrams (mg)/ APAP 325 mg every 6 hours (q6h) for 2 days.

Drug: HB/APAP

VX-548: Low Dose

EXPERIMENTAL

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

VX-548: Mid Dose

EXPERIMENTAL

Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.

Drug: VX-548

VX-548: High Dose

EXPERIMENTAL

Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.

Drug: VX-548

Interventions

VX-548 DRUG

Tablets for oral administration.

Also known as: Suzetrigine

VX-548: High Dose; VX-548: Low Dose; VX-548: Mid Dose

HB/APAP DRUG

Capsules for oral administration.

HB/APAP

Placebo (matched to VX-548) DRUG

Placebo matched to VX-548 for oral administration.

Placebo

Placebo (matched to HB/APAP) DRUG

Placebo matched to HB/APAP for oral administration.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (12)

Shoals Medical Trials Inc.

Sheffield, Alabama, 35660, United States

Location

Arizona Research Center

Phoenix, Arizona, 85053, United States

Location

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Lotus Clinical Research

Pasadena, California, 91105, United States

Location

New Hope Research Development

Tarzana, California, 91356, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Chesapeake Research Group

Pasadena, Maryland, 21122, United States

Location

Midwest Clinical Research Center

Dayton, Ohio, 45417, United States

Location

First Surgical Hospital

Bellaire, Texas, 77401, United States

Location

Legent Orthopedic Hospital

Carrollton, Texas, 75006, United States

Location

Endeavor Clinical Trials

San Antonio, Texas, 78229, United States

Location

JBR Clinical Research

Salt Lake City, Utah, 84107, United States

Location

Related Publications (2)

• Jones J, Correll DJ, Lechner SM, Jazic I, Miao X, Shaw D, Simard C, Osteen JD, Hare B, Beaton A, Bertoch T, Buvanendran A, Habib AS, Pizzi LJ, Pollak RA, Weiner SG, Bozic C, Negulescu P, White PF; VX21-548-101 and VX21-548-102 Trial Groups. Selective Inhibition of NaV1.8 with VX-548 for Acute Pain. N Engl J Med. 2023 Aug 3;389(5):393-405. doi: 10.1056/NEJMoa2209870.

  PMID: 37530822 DERIVED

• Russo MA, Baron R, Dickenson AH, Kern KU, Santarelli DM. Ambroxol for neuropathic pain: hiding in plain sight? Pain. 2023 Jan 1;164(1):3-13. doi: 10.1097/j.pain.0000000000002693. Epub 2022 May 17.

  PMID: 35580314 DERIVED

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: July 26, 2021
• Study Start: July 19, 2021
• Primary Completion: February 17, 2022
• Study Completion: March 4, 2022
• Last Updated: June 25, 2025
• Results First Posted: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)