Acute Pain
Conditions
Brief summary
This study will evaluate the dose-response relationship and safety of VX-150 in treating acute pain following bunionectomy.
Interventions
DRUGVX-150
Capsules for oral administration.
DRUGPlacebo
Capsules for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Before surgery: * Body mass index (BMI) of 18.0 to 38.0 kilogram per meter square (kg/m\^2) * Be scheduled to undergo a primary unilateral first metatarsal bunionectomy repair, without collateral procedures, under regional anesthesia (Mayo and popliteal sciatic block) not to include base wedge procedure After surgery: * Subject reported pain of greater than or equal to (\>=) 4 on Numeric Pain Rating Scale (NPRS) and moderate or severe pain on the Verbal Categorical Rating Scale (VRS) within 9 hours after removal of the popliteal sciatic block on Day 1 * Subject is lucid and able to follow commands * All analgesic guidelines were followed during and after the bunionectomy Key
Exclusion criteria
Before surgery: * History in the past 10 years of malignancy, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ * History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s) * History of abnormal laboratory results \>=2.5\*upper limit of normal (ULN) * History of peripheral neuropathy * A known or clinically suspected infection with human immunodeficiency virus or hepatitis B or C viruses * Prior medical history of bunionectomy or other foot surgery on the index foot * History of peptic ulcer disease, or intolerance or unwillingness to receive ibuprofen After surgery: * Subject had a type 3 deformity requiring a base wedge osteotomy or concomitant surgery Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose | 0 to 24 Hours After First Dose | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo | From Baseline at 24 Hours After First Dose | Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported. |
| Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | From Baseline at 24 Hours After First Dose | Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported. |
| Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | From Baseline at 24 Hours After First Dose | Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported. |
| Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo | Up to 6 hours After the First Dose | Time to onset of confirmed perceptible pain relief (time to onset of perceptible pain relief \[any pain relief at all after the first dose\] for participants who had meaningful pain relief \[relief that is meaningful to participants after the first dose\] reported based on the stopwatch assessment. |
| Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose | 0 to 48 Hours After First Dose | 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). |
| Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | Day 1 and Day 2 | — |
| Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | Day 1 and Day 2 | — |
| Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 up to Day 10 | — |
| Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo | Up to 6 Hours After the First Dose | Time to onset of meaningful pain relief (relief that is meaningful to participants after the first dose) reported based on the stopwatch assessment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to VX-150 for 2 days. | 46 |
| VX-150 - Dose Level 1 Participants received VX-150 1500 mg as first dose, followed by VX-150 750 mg q12h for 2 days. | 42 |
| VX-150 - Dose Level 2 Participants received VX-150 1000 mg qd for 2 days. | 44 |
| VX-150 - Dose Level 3 Participants received VX-150 500 mg q12h for 2 days. | 45 |
| VX-150 - Dose Level 4 Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days. | 46 |
| VX-150 - Dose Level 5 Participants received VX-150 250 mg qd for 2 days. | 27 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal of consent (due to lack of efficacy) | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal of consent (for other reason) | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | VX-150 - Dose Level 1 | VX-150 - Dose Level 2 | VX-150 - Dose Level 3 | VX-150 - Dose Level 4 | VX-150 - Dose Level 5 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 14.21 | 44.6 years STANDARD_DEVIATION 13.03 | 44.7 years STANDARD_DEVIATION 13.23 | 46.4 years STANDARD_DEVIATION 12.18 | 47.2 years STANDARD_DEVIATION 11.51 | 48.7 years STANDARD_DEVIATION 12.92 | 46.2 years STANDARD_DEVIATION 12.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 14 Participants | 15 Participants | 13 Participants | 16 Participants | 8 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 28 Participants | 29 Participants | 32 Participants | 30 Participants | 19 Participants | 168 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Pain Intensity at Baseline (at 0 hours) as Recorded on Numeric Pain Rating Scale (NPRS) | 6.5 units on a scale STANDARD_DEVIATION 1.8 | 7.0 units on a scale STANDARD_DEVIATION 2 | 6.5 units on a scale STANDARD_DEVIATION 1.8 | 6.6 units on a scale STANDARD_DEVIATION 1.7 | 5.9 units on a scale STANDARD_DEVIATION 1.3 | 6.9 units on a scale STANDARD_DEVIATION 1.6 | 6.5 units on a scale STANDARD_DEVIATION 1.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 13 Participants | 10 Participants | 6 Participants | 3 Participants | 39 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 38 Participants | 35 Participants | 27 Participants | 31 Participants | 34 Participants | 23 Participants | 188 Participants |
| Sex: Female, Male Female | 40 Participants | 37 Participants | 40 Participants | 39 Participants | 40 Participants | 21 Participants | 217 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 42 | 0 / 44 | 0 / 45 | 0 / 46 | 0 / 27 |
| other Total, other adverse events | 7 / 46 | 9 / 42 | 13 / 44 | 12 / 45 | 12 / 46 | 4 / 27 |
| serious Total, serious adverse events | 0 / 46 | 0 / 42 | 0 / 44 | 0 / 45 | 0 / 46 | 1 / 27 |
Outcome results
Primary
Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose
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).
Time frame: 0 to 24 Hours After First Dose
Population: Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose | 19.1 units on a scale | Standard Deviation 49.7 |
| VX-150 - Dose Level 1 | Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose | 37.3 units on a scale | Standard Deviation 45.6 |
| VX-150 - Dose Level 2 | Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose | 32.3 units on a scale | Standard Deviation 51.2 |
| VX-150 - Dose Level 3 | Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose | 30.5 units on a scale | Standard Deviation 46.9 |
| VX-150 - Dose Level 4 | Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose | 27.5 units on a scale | Standard Deviation 37.8 |
| VX-150 - Dose Level 5 | Time-weighted Sum of the Pain Intensity Difference as Recorded on Numeric Pain Rating Scale (NPRS) 0 to 24 Hours (SPID24) After First Dose | 28.3 units on a scale | Standard Deviation 43.6 |
p-value: 0.2107Multiple Comparison Procedure-Modelling
p-value: 0.0766Multiple Comparison Procedure-Modelling
p-value: 0.0989Multiple Comparison Procedure-Modelling
p-value: 0.0927Multiple Comparison Procedure-Modelling
Secondary
Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114
Time frame: Day 1 and Day 2
Population: PK set. Here, number analyzed signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 1 | 39.7 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 13.4 |
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 2 | 46.1 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 14 |
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 1 | 13.7 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 4.4 |
| Placebo | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 2 | 26.8 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 9.6 |
| VX-150 - Dose Level 1 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 1 | 25.7 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 11 |
| VX-150 - Dose Level 1 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 2 | 17.6 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 7.33 |
| VX-150 - Dose Level 1 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 2 | 36.1 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 12.8 |
| VX-150 - Dose Level 1 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 1 | 10.2 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 4.84 |
| VX-150 - Dose Level 2 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 2 | 16.2 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 4.72 |
| VX-150 - Dose Level 2 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 2 | 27.1 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 8.4 |
| VX-150 - Dose Level 2 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 1 | 5.55 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 2.04 |
| VX-150 - Dose Level 2 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 1 | 13.6 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 4.6 |
| VX-150 - Dose Level 3 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 1 | 14.6 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 4.73 |
| VX-150 - Dose Level 3 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 2 | 17.7 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 6.01 |
| VX-150 - Dose Level 3 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 2 | 10.8 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 4.19 |
| VX-150 - Dose Level 3 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 1 | 5.48 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 2.58 |
| VX-150 - Dose Level 4 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 2 | 3.84 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 1.39 |
| VX-150 - Dose Level 4 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1268114: Day 1 | 2.27 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 1.01 |
| VX-150 - Dose Level 4 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 2 | 8.24 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 2.8 |
| VX-150 - Dose Level 4 | Area Under the Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12h) of VRT- 1207355 and VRT- 1268114 | VRT- 1207355: Day 1 | 5.99 microgram*hour per milliliter (mcg*h/mL) | Standard Deviation 1.68 |
Secondary
Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5)
Time frame: Day 1 and Day 2
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 1 | 4.97 micrograms per milliliter (mcg/mL) | Standard Deviation 1.67 |
| Placebo | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 2 | 4.93 micrograms per milliliter (mcg/mL) | Standard Deviation 1.38 |
| Placebo | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 1 | 1.79 micrograms per milliliter (mcg/mL) | Standard Deviation 0.637 |
| Placebo | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 2 | 2.68 micrograms per milliliter (mcg/mL) | Standard Deviation 0.944 |
| VX-150 - Dose Level 1 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 1 | 3.27 micrograms per milliliter (mcg/mL) | Standard Deviation 1.35 |
| VX-150 - Dose Level 1 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 2 | 1.87 micrograms per milliliter (mcg/mL) | Standard Deviation 0.779 |
| VX-150 - Dose Level 1 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 2 | 4.17 micrograms per milliliter (mcg/mL) | Standard Deviation 1.53 |
| VX-150 - Dose Level 1 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 1 | 1.31 micrograms per milliliter (mcg/mL) | Standard Deviation 0.602 |
| VX-150 - Dose Level 2 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 2 | 1.65 micrograms per milliliter (mcg/mL) | Standard Deviation 0.544 |
| VX-150 - Dose Level 2 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 2 | 3.00 micrograms per milliliter (mcg/mL) | Standard Deviation 0.979 |
| VX-150 - Dose Level 2 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 1 | 0.699 micrograms per milliliter (mcg/mL) | Standard Deviation 0.261 |
| VX-150 - Dose Level 2 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 1 | 1.71 micrograms per milliliter (mcg/mL) | Standard Deviation 0.536 |
| VX-150 - Dose Level 3 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 1 | 1.89 micrograms per milliliter (mcg/mL) | Standard Deviation 0.641 |
| VX-150 - Dose Level 3 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 2 | 1.95 micrograms per milliliter (mcg/mL) | Standard Deviation 0.708 |
| VX-150 - Dose Level 3 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 2 | 1.11 micrograms per milliliter (mcg/mL) | Standard Deviation 0.437 |
| VX-150 - Dose Level 3 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 1 | 0.719 micrograms per milliliter (mcg/mL) | Standard Deviation 0.341 |
| VX-150 - Dose Level 4 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 2 | 0.408 micrograms per milliliter (mcg/mL) | Standard Deviation 0.153 |
| VX-150 - Dose Level 4 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1268114: Day 1 | 0.295 micrograms per milliliter (mcg/mL) | Standard Deviation 0.128 |
| VX-150 - Dose Level 4 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 2 | 0.974 micrograms per milliliter (mcg/mL) | Standard Deviation 0.305 |
| VX-150 - Dose Level 4 | Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) | VRT- 1207355: Day 1 | 0.794 micrograms per milliliter (mcg/mL) | Standard Deviation 0.241 |
Secondary
Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo
Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported.
Time frame: From Baseline at 24 Hours After First Dose
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo | 50.0 percentage of participants |
| VX-150 - Dose Level 1 | Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo | 59.5 percentage of participants |
| VX-150 - Dose Level 2 | Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo | 56.8 percentage of participants |
| VX-150 - Dose Level 3 | Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo | 55.6 percentage of participants |
| VX-150 - Dose Level 4 | Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo | 63.0 percentage of participants |
| VX-150 - Dose Level 5 | Proportion of Participants With at Least 30 Percent (%) Reduction in NPRS at 24 Hours After First Dose of VX-150 Versus Placebo | 51.9 percentage of participants |
p-value: 0.3162Cochran-Mantel-Haenszel
p-value: 0.4613Cochran-Mantel-Haenszel
p-value: 0.4095Cochran-Mantel-Haenszel
p-value: 0.157Cochran-Mantel-Haenszel
p-value: 0.9843Cochran-Mantel-Haenszel
Secondary
Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo
Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported.
Time frame: From Baseline at 24 Hours After First Dose
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 41.3 percentage of participants |
| VX-150 - Dose Level 1 | Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 38.1 percentage of participants |
| VX-150 - Dose Level 2 | Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 45.5 percentage of participants |
| VX-150 - Dose Level 3 | Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 44.4 percentage of participants |
| VX-150 - Dose Level 4 | Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 45.7 percentage of participants |
| VX-150 - Dose Level 5 | Proportion of Participants With at Least 50% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 40.7 percentage of participants |
p-value: 0.8714Cochran-Mantel-Haenszel
p-value: 0.5815Cochran-Mantel-Haenszel
p-value: 0.4308Cochran-Mantel-Haenszel
p-value: 0.4434Cochran-Mantel-Haenszel
p-value: 0.855Cochran-Mantel-Haenszel
Secondary
Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo
Pain intensity was recorded on 11-point ordinal 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 24 hours after the first dose of VX-150 or placebo were reported.
Time frame: From Baseline at 24 Hours After First Dose
Population: FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 21.7 percentage of participants |
| VX-150 - Dose Level 1 | Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 21.4 percentage of participants |
| VX-150 - Dose Level 2 | Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 34.1 percentage of participants |
| VX-150 - Dose Level 3 | Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 22.2 percentage of participants |
| VX-150 - Dose Level 4 | Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 30.4 percentage of participants |
| VX-150 - Dose Level 5 | Proportion of Participants With at Least 70% Reduction in NPRS at 24 Hours After the First Dose of VX-150 Versus Placebo | 18.5 percentage of participants |
p-value: 0.687Cochran-Mantel-Haenszel
p-value: 0.1515Cochran-Mantel-Haenszel
p-value: 0.603Cochran-Mantel-Haenszel
p-value: 0.1361Cochran-Mantel-Haenszel
p-value: 0.564Cochran-Mantel-Haenszel
Secondary
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Day 10
Population: Safety set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 15 participants |
| Placebo | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| VX-150 - Dose Level 1 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 16 participants |
| VX-150 - Dose Level 1 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| VX-150 - Dose Level 2 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 19 participants |
| VX-150 - Dose Level 2 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| VX-150 - Dose Level 3 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 18 participants |
| VX-150 - Dose Level 3 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| VX-150 - Dose Level 4 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 19 participants |
| VX-150 - Dose Level 4 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 0 participants |
| VX-150 - Dose Level 5 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With AEs | 12 participants |
| VX-150 - Dose Level 5 | Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants With SAEs | 1 participants |
Secondary
Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo
Time to onset of confirmed perceptible pain relief (time to onset of perceptible pain relief \[any pain relief at all after the first dose\] for participants who had meaningful pain relief \[relief that is meaningful to participants after the first dose\] reported based on the stopwatch assessment.
Time frame: Up to 6 hours After the First Dose
Population: FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo | 20.4 minutes |
| VX-150 - Dose Level 1 | Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo | 29.6 minutes |
| VX-150 - Dose Level 2 | Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo | 23.8 minutes |
| VX-150 - Dose Level 3 | Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo | 20.2 minutes |
| VX-150 - Dose Level 4 | Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo | 35.6 minutes |
| VX-150 - Dose Level 5 | Time to Onset of Confirmed Perceptible Pain Relief After First Dose of VX-150 Versus Placebo | 25.2 minutes |
p-value: 0.540595% CI: [0.6, 2.67]Regression, Cox
p-value: 0.901195% CI: [0.49, 2.27]Regression, Cox
p-value: 0.912795% CI: [0.48, 2.26]Regression, Cox
p-value: 0.561995% CI: [0.6, 2.56]Regression, Cox
p-value: 0.70995% CI: [0.5, 2.79]Regression, Cox
Secondary
Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo
Time to onset of meaningful pain relief (relief that is meaningful to participants after the first dose) reported based on the stopwatch assessment.
Time frame: Up to 6 Hours After the First Dose
Population: FAS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo | 55.4 minutes |
| VX-150 - Dose Level 1 | Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo | 58.7 minutes |
| VX-150 - Dose Level 2 | Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo | 68.6 minutes |
| VX-150 - Dose Level 3 | Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo | 49.9 minutes |
| VX-150 - Dose Level 4 | Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo | 61.5 minutes |
| VX-150 - Dose Level 5 | Time to Onset of Meaningful Pain Relief After the First Dose of VX-150 Versus Placebo | 64.5 minutes |
p-value: 0.975695% CI: [0.46, 2.14]Regression, Cox
p-value: 0.558295% CI: [0.6, 2.57]Regression, Cox
p-value: 0.754395% CI: [0.49, 2.71]Regression, Cox
p-value: 0.514195% CI: [0.61, 2.72]Regression, Cox
p-value: 0.961495% CI: [0.45, 2.12]Regression, Cox
Secondary
Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose
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).
Time frame: 0 to 48 Hours After First Dose
Population: FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose | 77.4 units on a scale | Standard Deviation 105.2 |
| VX-150 - Dose Level 1 | Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose | 112.5 units on a scale | Standard Deviation 88.4 |
| VX-150 - Dose Level 2 | Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose | 106.1 units on a scale | Standard Deviation 109.6 |
| VX-150 - Dose Level 3 | Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose | 101.5 units on a scale | Standard Deviation 103.2 |
| VX-150 - Dose Level 4 | Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose | 90.9 units on a scale | Standard Deviation 81.9 |
| VX-150 - Dose Level 5 | Time-weighted Sum of Pain Intensity Difference as Recorded on NPRS 0 to 48 Hours (SPID48) After First Dose | 100.0 units on a scale | Standard Deviation 102.6 |