A Phase 1, First-in-human Study of VX-828

Study Overview
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Brief Summary
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The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics of VX-828 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, First-in-human Study of Safety, Tolerability, and Pharmacokinetics of VX-828

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-828
* Drug: Placebo
* Drug: Itraconazole
* Drug: Midazolam


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) A total body weight of more than (>) 50 kg Nonsmoker or ex-smoker for at least 3 months before screening with current nonsmoking status confirmed by urine or blood cotinine at screening Key Exclusion Criteria: History of febrile illness or other acute illness within 14 days before the first dose of study drug Any condition possibly affecting drug absorption Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single Ascending Dose (SAD)<br>Participants will be randomized to receive a single dose of different dose levels of VX-828. | Drug: VX-828<br>* Suspension for Oral Administration<br>|
| Placebo Comparator: Part A: Placebo<br>Participants will be randomized to receive placebo matched to VX-828. | Drug: Placebo<br>* Suspension for Oral Administration<br>|
| Experimental: Part B: Multiple Ascending Dose (MAD)<br>Participants will be randomized to receive multiple doses of different dose levels of VX-828. The dose levels will be determined based on the data from Part A. | Drug: VX-828<br>* Suspension for Oral Administration<br>|
| Placebo Comparator: Part B: Placebo<br>Participants will be randomized to receive placebo matched to VX-828. | Drug: Placebo<br>* Suspension for Oral Administration<br>|
| Experimental: Part C: Drug Drug Interaction<br>Participants will receive a single dose of VX-828, followed by a washout period, Itraconazole administration, and concomitant administration of itraconazole and VX-828; or participants will receive Midazolam followed by VX-828 administration, and concomitant administration of VX-828 and Midazolam. Part C will be an open-label optional cohort. | Drug: VX-828<br>* Suspension for Oral Administration<br>Drug: Itraconazole<br>* Solution for Oral Administration<br>Drug: Midazolam<br>* Syrup for Oral Administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 17) | 
| Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 28) | 
| Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole |  | From Day 1 up to Day 34 | 
| Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole |  | From Day 1 up to Day 34 | 
| Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828 |  | From Day 1 up to Day 17 | 
| Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in Plasma in the Absence and Presence of VX-828 |  | From Day 1 up to Day 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Maximum Observed Concentration (Cmax) of VX-828 in Plasma |  | From Day 1 up to Day 15 | 
| Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma |  | From Day 1 up to Day 15 | 
| Part B: Maximum Observed Concentration (Cmax) of VX-828 at Steady State in Plasma |  | From Day 1 up to Day 28 | 
| Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Steady State in Plasma |  | From Day 1 up to Day 28 | 
| Part C: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Baseline up to Day 35 |