Trial Outcomes & Findings for Evaluation of Efficacy and Safety of VX-548 for Acute Pain After a Bunionectomy (NCT NCT05553366)

NCT ID: NCT05553366

Last Updated: 2025-08-01

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1075 participants

Primary outcome timeframe

0 to 48 hours After First Dose of Study Drug

Results posted on

2025-08-01

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo
Participants received placebo matched to suzetrigine (SUZ) and hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days.
Hydrocodone Bitartrate/Acetaminophen (HB/APAP)
Participants received HB 5 milligrams (mg)/ APAP 325 mg every 6 hours (q6h) for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg every 12 hours (q12h)\] for 2 days.
Overall Study
STARTED
216
431
428
Overall Study
Safety Set
216
431
426
Overall Study
COMPLETED
208
419
418
Overall Study
NOT COMPLETED
8
12
10

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Participants received placebo matched to suzetrigine (SUZ) and hydrocodone bitartrate/acetaminophen (HB/APAP) for 2 days.
Hydrocodone Bitartrate/Acetaminophen (HB/APAP)
Participants received HB 5 milligrams (mg)/ APAP 325 mg every 6 hours (q6h) for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg every 12 hours (q12h)\] for 2 days.
Overall Study
Withdrawal of Consent (not due to AE
4
8
5
Overall Study
Lost to Follow-up
3
3
3
Overall Study
Other non-compliance
1
1
0
Overall Study
Randomized but not dosed
0
0
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Hydrocodone Bitartrate/Acetaminophen (HB/APAP)
n=431 Participants
Participants received HB 5 mg/ APAP 325 mg q6h for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Total
n=1073 Participants
Total of all reporting groups
Age, Continuous
48.1 years
STANDARD_DEVIATION 13.5 • n=5 Participants
48.3 years
STANDARD_DEVIATION 12.6 • n=7 Participants
47.7 years
STANDARD_DEVIATION 13.3 • n=5 Participants
48.0 years
STANDARD_DEVIATION 13.1 • n=4 Participants
Sex: Female, Male
Female
187 Participants
n=5 Participants
359 Participants
n=7 Participants
366 Participants
n=5 Participants
912 Participants
n=4 Participants
Sex: Female, Male
Male
29 Participants
n=5 Participants
72 Participants
n=7 Participants
60 Participants
n=5 Participants
161 Participants
n=4 Participants
Race/Ethnicity, Customized
Hispanic or Latino
84 Participants
n=5 Participants
149 Participants
n=7 Participants
131 Participants
n=5 Participants
364 Participants
n=4 Participants
Race/Ethnicity, Customized
Not Hispanic or Latino
132 Participants
n=5 Participants
282 Participants
n=7 Participants
295 Participants
n=5 Participants
709 Participants
n=4 Participants
Race/Ethnicity, Customized
White
160 Participants
n=5 Participants
314 Participants
n=7 Participants
285 Participants
n=5 Participants
759 Participants
n=4 Participants
Race/Ethnicity, Customized
Black or African American
48 Participants
n=5 Participants
96 Participants
n=7 Participants
116 Participants
n=5 Participants
260 Participants
n=4 Participants
Race/Ethnicity, Customized
Asian
8 Participants
n=5 Participants
7 Participants
n=7 Participants
9 Participants
n=5 Participants
24 Participants
n=4 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
0 Participants
n=5 Participants
7 Participants
n=7 Participants
4 Participants
n=5 Participants
11 Participants
n=4 Participants
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
Race/Ethnicity, Customized
Other
0 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants
5 Participants
n=4 Participants
Race/Ethnicity, Customized
Multiracial
0 Participants
n=5 Participants
3 Participants
n=7 Participants
6 Participants
n=5 Participants
9 Participants
n=4 Participants
Race/Ethnicity, Customized
Missing
0 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
3 Participants
n=4 Participants

PRIMARY outcome

Timeframe: 0 to 48 hours After First Dose of Study Drug

Population: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

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).

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
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
70.6 units on a scale
Standard Error 6.3
99.9 units on a scale
Standard Error 4.5

SECONDARY outcome

Timeframe: 0 to 48 hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure.

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).

Outcome measures

Outcome measures
Measure
Placebo
n=431 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
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
120.1 units on a scale
Standard Error 4.5
99.9 units on a scale
Standard Error 4.5

SECONDARY outcome

Timeframe: From Baseline Up to 48 Hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Time to Greater Than or Equal to (≥)2-Point Reduction in NPRS,SUZ Compared to Placebo
480 minutes
Interval 476.0 to 716.0
240 minutes
Interval 117.0 to 477.0

SECONDARY outcome

Timeframe: From Baseline Up to 48 Hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Time to ≥1-Point Reduction in NPRS, SUZ Compared to Placebo
61 minutes
Interval 34.0 to 121.0
60 minutes
Interval 58.0 to 65.0

SECONDARY outcome

Timeframe: At 48 Hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Percentage of Participants Reporting Good or Excellent on the Patient Global Assessment (PGA) Scale, SUZ Compared to Placebo
53.2 percentage of participants
61.7 percentage of participants

SECONDARY outcome

Timeframe: From Baseline up to Day 19

Population: Safety Set included all participants who received at least 1 dose of study drug. Data for this outcome measure was planned to be collected and analyzed only for the HB/APAP and SUZ group.

The percentage of participants with the events of vomiting or nausea during the specified time frame was reported.

Outcome measures

Outcome measures
Measure
Placebo
n=431 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Incidence of Vomiting or Nausea, SUZ Compared to HB/APAP
16.5 percentage of participants
9.2 percentage of participants

SECONDARY outcome

Timeframe: 0 to 24 Hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.

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).

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Time-weighted SPID as Recorded on the NPRS From 0 to 24 Hours (SPID24), SUZ Compared to Placebo
19.8 units on a scale
Standard Error 3.0
30.6 units on a scale
Standard Error 2.1

SECONDARY outcome

Timeframe: 0 to 48 Hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.

Time to first use of rescue medication is the time from the first dose of study drug until the first use of rescue medication.

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Time to First Use of Rescue Medication, SUZ Compared to Placebo
185 minutes
Interval 143.0 to 210.0
157 minutes
Interval 145.0 to 192.0

SECONDARY outcome

Timeframe: 0 to 48 Hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Percentage of Participants Using Rescue Medication From 0 to 48 Hours, SUZ Compared to Placebo
85.6 percentage of participants
85.4 percentage of participants

SECONDARY outcome

Timeframe: 0 to 48 Hours After First Dose of Study Drug

Population: FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were evaluated for this specific outcome measure. Data for this outcome measure was planned to be collected and analyzed only for the Placebo and SUZ group.

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Total Rescue Medication Usage, SUZ Compared to Placebo
800 milligram
Interval 0.0 to 3200.0
800 milligram
Interval 0.0 to 3200.0

SECONDARY outcome

Timeframe: Day 1 up to Day 19

Population: Safety Set included all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure
Placebo
n=216 Participants
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Suzetrigine (SUZ)
n=431 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Suzetrigine (SUZ)
n=426 Participants
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants with TEAEs
76 Participants
180 Participants
132 Participants
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants with SAEs
0 Participants
0 Participants
0 Participants

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 51 other events
Deaths: 0 deaths

Hydrocodone Bitartrate/Acetaminophen (HB/APAP)

Serious events: 0 serious events
Other events: 113 other events
Deaths: 0 deaths

Suzetrigine (SUZ)

Serious events: 0 serious events
Other events: 72 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Placebo
n=216 participants at risk
Participants received placebo matched to SUZ and HB/APAP for 2 days.
Hydrocodone Bitartrate/Acetaminophen (HB/APAP)
n=431 participants at risk
Participants received HB 5 mg/ APAP 325 mg q6h for 2 days.
Suzetrigine (SUZ)
n=426 participants at risk
Participants received SUZ \[100 mg as first dose, followed by 50 mg q12h\] for 2 days.
Gastrointestinal disorders
Constipation
4.2%
9/216 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
5.1%
22/431 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
3.5%
15/426 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
Gastrointestinal disorders
Nausea
10.6%
23/216 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
14.4%
62/431 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
8.2%
35/426 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
Nervous system disorders
Dizziness
5.1%
11/216 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
5.3%
23/431 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
3.5%
15/426 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
Nervous system disorders
Headache
9.3%
20/216 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
10.4%
45/431 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.
4.9%
21/426 • Day 1 up to Day 19
Safety Set included all participants who received at least 1 dose of the study drug.

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place