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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: VX-150; Drug: HB/APAP; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Participants received placebo matched to VX-150 and HB/APAP for 2 days.
Experimental: VX-150	Drug: 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.
Active Comparator: Hydrocodone Bitartrate/Acetaminophen (HB/APAP)	Drug: HB/APAP; Participants received HB 5 mg/APAP 325 mg every 6 hours (q6h) for 2 days.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2017
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 8, 2017

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: VX16-150-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No