Acute PainPhase 2NCT04977336

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

A Phase 2 study testing VX-548 and HB/APAP in people with Acute Pain, run by Vertex Pharmaceuticals Incorporated at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Acute Pain
What is being tested?: VX-548 and HB/APAP
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 274 participants
Where: 12 sitesUnited States
Study dates: 19 Jul 2021to 4 Mar 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

United States12 sites

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

Other trials in United States

About this study

Official title: 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.

Conditions: Acute Pain
Being tested: VX-548, HB/APAP, Placebo (matched to VX-548), Placebo (matched to HB/APAP)
Medical subject headings: Acute Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VX-548Drug
Also called Suzetrigine
Tablets for oral administration.
HB/APAPDrug
Capsules for oral administration.
Placebo (matched to VX-548)Drug
Placebo matched to VX-548 for oral administration.
Placebo (matched to HB/APAP)Drug
Placebo matched to HB/APAP for oral administration.

Study groups in NCT04977336
Study group	Role	What they receive
Placebo	Placebo comparator	Participants received placebo matched to VX-548 and Hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: VX-548

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Baseline at 48 Hours After First Dose of Study Drug
Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite)
Measured: Day 1 and Day 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite)
Measured: 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)
Measured: Day 1 and Day 2
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Day 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Jul 20214 Mar 2022

First posted26 Jul 2021
Study start19 Jul 2021
Primary completion17 Feb 2022
Study completion4 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Acute PainStudies of the same condition, open and under way.
More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 274 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04977336
Sponsor's protocol ID: VX21-548-101
Status last verified: Jun 2025
First submitted: 15 Jul 2021
Last updated: 25 Jun 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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

Publications

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.
PubMed 37530822
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.
PubMed 35580314

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acute Pain trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04977336
Acronym / sponsor ID: VX21-548-101
Conditions: Acute Pain
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 274 participants (actual)
Lead sponsor: Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
Study start: 19 Jul 2021 (actual)
Primary completion: 17 Feb 2022 (actual)
Study completion: 4 Mar 2022 (actual)
First posted: 26 Jul 2021 (actual)
Results: Posted 25 Jun 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebo (matched to VX-548), Drug: Placebo (matched to HB/APAP)Participants received placebo matched to VX-548 and Hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days.
HB/APAP	Active comparator	Drug: HB/APAPParticipants received HB 5 milligrams (mg)/ APAP 325 mg every 6 hours (q6h) for 2 days.
VX-548: Low Dose	Experimental	Drug: VX-548Participants received VX-548 20 mg as first dose, followed by VX-548 10 mg tablet every 12 hours (q12h) for 2 days.
VX-548: Mid Dose	Experimental	Drug: VX-548Participants received VX-548 60 mg as first dose, followed by VX-548 30 mg q12h for 2 days.
VX-548: High Dose	Experimental	Drug: VX-548Participants received VX-548 100 mg as first dose, followed by VX-548 50 mg q12h for 2 days.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Before Surgery:
After Surgery:

Key exclusion criteria (7 listed)

Before Surgery:
After Surgery:
Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VX-548Also: SuzetrigineTablets for oral administration.	Drug	VX-548: High Dose, VX-548: Low Dose, VX-548: Mid Dose
HB/APAPCapsules for oral administration.	Drug	HB/APAP
Placebo (matched to VX-548)Placebo matched to VX-548 for oral administration.	Drug	Placebo
Placebo (matched to HB/APAP)Placebo matched to HB/APAP for oral administration.	Drug	Placebo

Primary outcome

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
Time frame: 0 to 48 hours After 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).

8 secondary outcomes

Time-Weighted SPID as Recorded on a NPRS 0 to 24 Hours (SPID24) After the First Dose of Study Drug
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Baseline at 48 Hours After First Dose of Study Drug
Maximum Observed Plasma Concentration (Cmax) of VX-548 and M6-548 (Metabolite)
Time frame: Day 1 and Day 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VX-548 and M6-548 (Metabolite)
Time frame: 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)
Time frame: Day 1 and Day 2
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Day 16

Results and safety

Results posted to the registry on 25 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	59	58
HB/APAP	60	60
VX-548: Low Dose	33	32
VX-548: Mid Dose	62	61
VX-548: High Dose	60	58

Primary outcome: 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

Time frame: 0 to 48 hours After First Dose of Study Drug. Least squares mean (Standard Error). Unit: units on a scale

Measure	Placebo n = 59	HB/APAP n = 60	VX-548: Low Dose n = 33	VX-548: Mid Dose n = 62	VX-548: High Dose n = 60
Value	100.98 (11.60)	115.64 (11.49)	112.92 (15.52)	86.87 (11.33)	137.77 (11.50)

Placebo vs HB/APAP: p = 0.3706, ANCOVA
Placebo vs VX-548: Low Dose: p = 0.5379, ANCOVA
Placebo vs VX-548: Mid Dose: p = 0.3859, ANCOVA

Population analysed: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 up to Day 16. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 59 (0%)	12 of 59 (20.3%)	0 of 59
HB/APAP	0 of 60 (0%)	13 of 60 (21.7%)	0 of 60
VX-548: Low Dose	0 of 33 (0%)	2 of 33 (6.1%)	0 of 33
VX-548: Mid Dose	0 of 62 (0%)	7 of 62 (11.3%)	0 of 62
VX-548: High Dose	0 of 60 (0%)	9 of 60 (15%)	0 of 60

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37530822Jones 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.
Derived from this study: PubMed 35580314Russo 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.
Individual participant dataSharing planned: No. 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

Related trials for Acute Pain

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VX-548 and HB/APAP in people with Acute Pain, run by Vertex Pharmaceuticals Incorporated at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 0 to 48 hours After First Dose of Study Drug). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04977336, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2025.