A Study to Evaluate Efficacy and Safety of VX-150 in Subjects With Acute Pain Following Bunionectomy

Study Overview
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Brief Summary
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This is a Phase 2 randomized, double-blind, placebo-controlled, 3-arm, parallel design study to evaluate the efficacy and safety of VX-150 in treating acute pain following bunionectomy.

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled, 3-arm, Parallel-design Study of the Efficacy and Safety of VX-150 for Acute Pain Following Bunionectomy

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: VX-150
* Drug: HB/APAP
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior to Surgery: Body mass index (BMI) of 18.0 to 38.0 kg/m2, inclusive 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 ≥4 on the 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 Exclusion Criteria: Prior to 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 Intolerant of or unwilling to receive hydrocodone, acetaminophen, or ibuprofen For female subjects: Pregnant, nursing, or planning to become pregnant during the study or within 90 days after the last study drug dose For male subjects: Male subjects with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days after the last study drug dose After Surgery: Subject had a type 3 deformity requiring a base wedge osteotomy or concomitant surgery such as hammertoe repair; or experienced medical complications during the bunionectomy that, in the opinion of the investigator, should preclude randomization Other protocol defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VX-150<br> | Drug: VX-150<br>* Participants received VX-150 1500 milligram (mg) as first dose, followed by VX-150 750 mg dose every 12 hours (q12h) for 2 days.<br>|
| Active Comparator: Hydrocodone Bitartrate/Acetaminophen (HB/APAP)<br> | Drug: HB/APAP<br>* Participants received HB 5 mg/APAP 325 mg every 6 hours (q6h) for 2 days.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Participants received placebo matched to VX-150 and HB/APAP for 2 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | 0 to 24 hours after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | 2 to 24 hours after the first dose | 
| 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 | SPID was calculated as the sum of the product of time (in hours) elapsed since previous measurements and pain intensity difference. Pain intensity difference was calculated by subtracting the pain intensity score at given post-dose time points from the baseline pain intensity scores (using pain rating score range: 0 =no pain to 10 =worst possible pain). SPID48 was calculated from 0 to 48 hours and the score range was -480 (worst score) to 480 (best score). | 0 to 48 hours after the first dose | 
| Time to Onset of Perceptible Pain Relief After the First Dose of VX-150 Versus Placebo | Time to onset of perceptible pain relief (any pain relief at all after the first dose) reported based on the first stopwatch assessment. | up to 6 hours after the first dose | 
| 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 second stopwatch assessment. | up to 6 hours after the first dose | 
| Time to First Rescue Medication After the First Dose of VX-150 Versus Placebo | 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. | up to 48 hours after the first dose | 
| Percentage of Participants Using Rescue Medication After the First Dose VX-150 Versus Placebo |  | 0 to 24 hours after the first dose and 24 to 48 hours after the first dose | 
| Total Rescue Medication Used After the First Dose of VX-150 Versus Placebo | 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). | 0 to 24 hours after the first dose and 24 to 48 hours after the first dose | 
| Maximum Observed Concentration (Cmax) of VRT- 1207355 (Active Moiety) and VRT- 1268114 (Metabolite M5) |  | Day 1 and Day 2 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of VRT- 1207355 and VRT- 1268114 |  | 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 Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Day 1 up to Day 10 |