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

A Phase 2B Randomized, Double-blind, Placebo-controlled, Dose-ranging, Parallel-design Study of the Efficacy and Safety of VX-150 for Acute Pain Following Bunionectomy

This study will evaluate the dose-response relationship and safety of VX-150 in treating acute pain following bunionectomy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Chesapeake Research Group
  • Texas
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical 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

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/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to VX-150 for 2 days.	Drug: Placebo; Capsules for oral administration.
Experimental: VX-150 - Dose Level 1; Participants received VX-150 1500 milligrams (mg) as first dose, followed by VX-150 750 mg every 12 hours (q12h) for 2 days.	Drug: VX-150; Capsules for oral administration.
Experimental: VX-150 - Dose Level 2; Participants received VX-150 1000 mg once daily (qd) for 2 days.	Drug: VX-150; Capsules for oral administration.
Experimental: VX-150 - Dose Level 3; Participants received VX-150 500 mg q12h for 2 days.	Drug: VX-150; Capsules for oral administration.
Experimental: VX-150 - Dose Level 4; Participants received VX-150 500 mg as first dose, followed by VX-150 250 mg q12h for 2 days.	Drug: VX-150; Capsules for oral administration.
Experimental: VX-150 - Dose Level 5; Participants received VX-150 250 mg qd for 2 days.	Drug: VX-150; Capsules for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	0 to 24 Hours After First Dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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).	0 to 48 Hours After First Dose
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.	From Baseline at 24 Hours After First Dose
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.	From Baseline at 24 Hours After First Dose
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.	From Baseline at 24 Hours After First Dose
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.	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 stopwatch assessment.	Up to 6 Hours After the First Dose
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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): January 17, 2019
• Study Completion (Actual): January 25, 2019

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: December 3, 2018
• First Posted (Actual): December 4, 2018

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: VX18-150-104

Drug and device information, study documents

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