An Electrocardiogram Study to Evaluate the Effect of Vanzacaftor on the QT/QTc Interval in Healthy Participants

A Phase 1, Randomized, Double-blind, Placebo- and Positive-controlled, Thorough QT/QTc Study of Vanzacaftor Monotherapy in Healthy Subjects

The purpose of this study is to evaluate the effect of Vanzacaftor (VNZ) on QTcF, as well as the pharmacokinetic (PK), safety, and tolerability of VNZ in healthy participants.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Vanzacaftor; Drug: Vanzacaftor Placebo; Drug: Moxifloxacin Placebo; Drug: Moxifloxacin

Detailed Description

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion - Tempe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• Body mass index (BMI) of 18.0 to 32.0 kilogram per meter square (Kg/m^2), both inclusive
• Male and female participants of age 18 to 45 years, both inclusive
• Serum potassium, calcium, and magnesium values within normal ranges

Key Exclusion Criteria:

• Median QTcF>450 msec on triplicate 12-lead ECGs
• History of conduction abnormalities

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Participants will receive VNZ-matching placebo, moxifloxacin-matching placebo and VNZ at different time points.	Drug: Vanzacaftor; Tablets for oral administration.; Drug: Vanzacaftor Placebo; Placebo for oral administration.; Drug: Moxifloxacin Placebo; Tablets for oral administration.
Active Comparator: Group 2A; Participants will receive VNZ-matching placebo, moxifloxacin, and moxifloxacin-matching placebo at different time points.	Drug: Vanzacaftor Placebo; Placebo for oral administration.; Drug: Moxifloxacin Placebo; Tablets for oral administration.; Drug: Moxifloxacin; Tablets for oral administration.
Active Comparator: Group 2B; Participants will receive VNZ-matching placebo, moxifloxacin-matching placebo and moxifloxacin at different time points.	Drug: Vanzacaftor Placebo; Placebo for oral administration.; Drug: Moxifloxacin Placebo; Tablets for oral administration.; Drug: Moxifloxacin; Tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in QT interval corrected by Fridericia's formula (QTcF)	From Baseline up to Day 23

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Heart Rate (HR)	From Baseline up to Day 23
Change in PR interval, segment	From Baseline up to Day 23
Change in QRS duration	From Baseline up to Day 23
Placebo-corrected Change in QTcF	From Baseline up to Day 23
Placebo-corrected Change in HR	From Baseline up to Day 23
Placebo-corrected Change in PR interval	From Baseline up to Day 23
Placebo-corrected Change in QRS duration	From Baseline up to Day 23
Number of Outliers for QTcF	From Baseline up to Day 23
Number of Outliers for HR	From Baseline up to Day 23
Number of Outliers for PR interval	From Baseline up to Day 23
Number of Outliers for QRS duration	From Baseline up to Day 23
Frequency of Treatment-emergent Changes of T-wave Morphology and U-wave Presence	From Baseline up to Day 23
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Day -2 up to Day 38
Maximum Observed Plasma Concentration (Cmax) of VNZ	Days 11 and 21
Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to 24 hours (AUC0-24h)) of VNZ	Days 11 and 21
Time Taken for VNZ to Reach Maximum Concentration (tmax)	Days 11 and 21

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Actual): June 14, 2023
• Study Completion (Actual): June 14, 2023

Study Registration Dates

• First Submitted: April 21, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination
• Other Study ID Numbers: VX22-121-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

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