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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.).

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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Vanzacaftor
* Drug: Vanzacaftor Placebo
* Drug: Moxifloxacin
* Drug: Moxifloxacin Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |