Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of VX-150 in Subjects With Acute Pain Following Bunionectomy (NCT NCT03206749)
NCT ID: NCT03206749
Last Updated: 2021-02-03
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 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).
COMPLETED
PHASE2
243 participants
0 to 24 hours after the first dose
2021-02-03
Participant Flow
Participant milestones
| Measure |
VX-150
Participants received VX-150 1500 milligram (mg) as first dose, followed by VX-150 750 mg dose every 12 hours (q12h) for 2 days.
|
Hydrocodone Bitartrate/Acetaminophen (HB/APAP)
Participants received HB 5 mg/APAP 325 mg every 6 hours (q6h) for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
80
|
81
|
82
|
|
Overall Study
COMPLETED
|
75
|
78
|
75
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
7
|
Reasons for withdrawal
| Measure |
VX-150
Participants received VX-150 1500 milligram (mg) as first dose, followed by VX-150 750 mg dose every 12 hours (q12h) for 2 days.
|
Hydrocodone Bitartrate/Acetaminophen (HB/APAP)
Participants received HB 5 mg/APAP 325 mg every 6 hours (q6h) for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Overall Study
Withdrawal of consent
|
5
|
3
|
6
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate Efficacy and Safety of VX-150 in Subjects With Acute Pain Following Bunionectomy
Baseline characteristics by cohort
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
HB/APAP
n=81 Participants
Participants received HB 5 mg/APAP 325 mg q6h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Total
n=243 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
44.4 years
STANDARD_DEVIATION 12.87 • n=5 Participants
|
44.8 years
STANDARD_DEVIATION 13.04 • n=7 Participants
|
45.0 years
STANDARD_DEVIATION 12.43 • n=5 Participants
|
44.7 years
STANDARD_DEVIATION 12.73 • n=4 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
193 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
21 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
62 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
59 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
181 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
8 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
17 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
56 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
52 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
166 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Pain Intensity at Baseline (at 0 hours) as Recorded on Numeric Pain Rating Scale (NPRS)
|
6.1 units on scale
STANDARD_DEVIATION 1.7 • n=5 Participants
|
6.6 units on scale
STANDARD_DEVIATION 1.6 • n=7 Participants
|
6.1 units on scale
STANDARD_DEVIATION 1.5 • n=5 Participants
|
6.3 units on scale
STANDARD_DEVIATION 1.6 • n=4 Participants
|
PRIMARY outcome
Timeframe: 0 to 24 hours after the first dosePopulation: Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
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).
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Time-weighted Sum of the Pain Intensity Difference (SPID) Between VX-150 Versus Placebo as Recorded on a Numeric Pain Rating Scale (NPRS) 0 to 24 Hours After the First Dose
|
36.14 units on a scale
Standard Error 5.15
|
6.64 units on a scale
Standard Error 5.03
|
—
|
SECONDARY outcome
Timeframe: 2 to 24 hours after the first dosePopulation: FAS. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
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). SPID22 was calculated from 2 to 24 hours and the score range was -220 (worst score) to 220 (best score).
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Time-weighted Sum of the Pain Intensity Difference Between VX-150 Versus Placebo as Recorded on a NPRS 2 to 24 Hours After the First Dose
|
34.95 units on a scale
Standard Error 4.93
|
6.43 units on a scale
Standard Error 4.82
|
—
|
SECONDARY outcome
Timeframe: 0 to 48 hours after the first dosePopulation: FAS. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
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).
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Time-weighted Sum of the Pain Intensity Difference Between VX-150 Versus Placebo as Recorded on a NPRS 0 to 48 Hours After the First Dose
|
112.22 units on a scale
Standard Error 10.57
|
49.43 units on a scale
Standard Error 10.33
|
—
|
SECONDARY outcome
Timeframe: up to 6 hours after the first dosePopulation: FAS. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
Time to onset of perceptible pain relief (any pain relief at all after the first dose) reported based on the first stopwatch assessment.
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Time to Onset of Perceptible Pain Relief After the First Dose of VX-150 Versus Placebo
|
26.8 minutes
Interval 2.0 to 177.0
|
28.3 minutes
Interval 5.0 to 239.0
|
—
|
SECONDARY outcome
Timeframe: up to 6 hours after the first dosePopulation: FAS. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
Time to onset of meaningful pain relief (relief that is meaningful to participants after the first dose) reported based on the second stopwatch assessment.
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo
|
53.4 minutes
Interval 8.0 to 359.0
|
75.9 minutes
Interval 27.0 to 358.0
|
—
|
SECONDARY outcome
Timeframe: up to 48 hours after the first dosePopulation: FAS. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
Time to first rescue medication was the time elapsed from the first dose of VX-150 or placebo until the participants received the first dose of rescue medication.
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Time to First Rescue Medication After the First Dose of VX-150 Versus Placebo
|
2.7 hours
Interval 0.5 to 42.7
|
2.3 hours
Interval 0.5 to 40.2
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours after the first dose and 24 to 48 hours after the first dosePopulation: FAS. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Percentage of Participants Using Rescue Medication After the First Dose VX-150 Versus Placebo
0 to 24 hours after the first dose
|
83.8 percentage of participants
|
89.0 percentage of participants
|
—
|
|
Percentage of Participants Using Rescue Medication After the First Dose VX-150 Versus Placebo
24 to 48 hours after the first dose
|
56.3 percentage of participants
|
69.5 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours after the first dose and 24 to 48 hours after the first dosePopulation: FAS. As a standard-of-care reference arm, the "HB/APAP" arm was not intended for statistical comparisons to VX-150.
Total use of rescue medication was calculated as the sum of number of capsules multiplied by capsule strength at each dosing occasion of rescue medication. Rescue medication was ibuprofen (400 mg \[oral\] every 4 hours (q4h) as needed).
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Total Rescue Medication Used After the First Dose of VX-150 Versus Placebo
0 to 24 hours after the first dose
|
800 mg
Standard Deviation 341.1
|
1084.9 mg
Standard Deviation 478.3
|
—
|
|
Total Rescue Medication Used After the First Dose of VX-150 Versus Placebo
24 to 48 hours after the first dose
|
577.8 mg
Standard Deviation 289.9
|
786.0 mg
Standard Deviation 413.8
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 2Population: The pharmacokinetic (PK) set included all randomized participants who received at least 1 dose of study drug. Here "Number Analyzed" signifies those participants who were evaluable at specified time points. This outcome measure is applicable to VX-150 arm only.
Outcome measures
| Measure |
VX-150
n=79 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5)
VRT- 1207355 Day 1
|
4.95 microgram per milliliter (mcg/mL)
Standard Deviation 2.00
|
—
|
—
|
|
Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5)
VRT- 1207355 Day 2
|
4.92 microgram per milliliter (mcg/mL)
Standard Deviation 1.61
|
—
|
—
|
|
Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5)
VRT- 1268114 Day 1
|
1.65 microgram per milliliter (mcg/mL)
Standard Deviation 0.779
|
—
|
—
|
|
Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5)
VRT- 1268114 Day 2
|
2.53 microgram per milliliter (mcg/mL)
Standard Deviation 0.797
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 2Population: PK set. Here "Number Analyzed" signifies those participants who were evaluable at specified time points. This outcome measure is applicable to VX-150 arm only.
Outcome measures
| Measure |
VX-150
n=79 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VRT- 1207355 and VRT- 1268114
VRT- 1207355 Day 2
|
4.03 hours
Interval 0.0 to 6.25
|
—
|
—
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VRT- 1207355 and VRT- 1268114
VRT- 1268114 Day 1
|
8.10 hours
Interval 1.08 to 12.3
|
—
|
—
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VRT- 1207355 and VRT- 1268114
VRT- 1207355 Day 1
|
5.58 hours
Interval 1.08 to 12.1
|
—
|
—
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of VRT- 1207355 and VRT- 1268114
VRT- 1268114 Day 2
|
4.03 hours
Interval 0.0 to 8.18
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 and Day 2Population: PK set. Here "Number Analyzed" signifies those participants who were evaluable at specified time points. This outcome measure is applicable to VX-150 arm only.
Outcome measures
| Measure |
VX-150
n=79 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114
VRT- 1207355 Day 1
|
38.8 microgram*hour per milliliter (mcg*h/mL)
Standard Deviation 15.9
|
—
|
—
|
|
Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114
VRT- 1207355 Day 2
|
45.7 microgram*hour per milliliter (mcg*h/mL)
Standard Deviation 15.5
|
—
|
—
|
|
Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114
VRT- 1268114 Day 1
|
12.9 microgram*hour per milliliter (mcg*h/mL)
Standard Deviation 6.20
|
—
|
—
|
|
Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114
VRT- 1268114 Day 2
|
25.0 microgram*hour per milliliter (mcg*h/mL)
Standard Deviation 7.95
|
—
|
—
|
SECONDARY outcome
Timeframe: From Day 1 up to Day 10Population: The Safety Set was included all participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
VX-150
n=80 Participants
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
Placebo
n=81 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
Placebo
n=82 Participants
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
25 participants
|
30 participants
|
29 participants
|
|
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
VX-150
HB/APAP
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
VX-150
n=80 participants at risk
Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days.
|
HB/APAP
n=81 participants at risk
Participants received HB 5 mg/APAP 325 mg q6h for 2 days.
|
Placebo
n=82 participants at risk
Participants received placebo matched to VX-150 and HB/APAP for 2 days.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
11.2%
9/80 • From Day 1 up to Day 10
|
12.3%
10/81 • From Day 1 up to Day 10
|
17.1%
14/82 • From Day 1 up to Day 10
|
|
Nervous system disorders
Dizziness
|
5.0%
4/80 • From Day 1 up to Day 10
|
7.4%
6/81 • From Day 1 up to Day 10
|
2.4%
2/82 • From Day 1 up to Day 10
|
|
Gastrointestinal disorders
Nausea
|
11.2%
9/80 • From Day 1 up to Day 10
|
19.8%
16/81 • From Day 1 up to Day 10
|
13.4%
11/82 • From Day 1 up to Day 10
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
4/80 • From Day 1 up to Day 10
|
8.6%
7/81 • From Day 1 up to Day 10
|
3.7%
3/82 • From Day 1 up to Day 10
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER