Evaluation of VX-828 in Healthy Participants and in Participants With Cystic Fibrosis

Vertex Pharmaceuticals Incorporated165 enrolled

Overview

The purpose of the study is to evaluate safety, tolerability, and pharmacokinetics of VX-828 and VX-828 in triple combination (TC) with Tezacaftor (TEZ)/ VX-118 or TEZ/ deutivacaftor (D-IVA) in healthy participants and VX-828 in combination with D-IVA with or without TEZ in participants with cystic fibrosis (CF).

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

165

Conditions

Cystic Fibrosis

Interventions

VX-828DRUG

Suspension for Oral Administration

PlaceboDRUG

Suspension for Oral Administration

ItraconazoleDRUG

Solution for Oral Administration

Midazolam

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: Parts A-D: * Participants between the ages of 18 and 55 years * 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 * Cohort C2 only: Willing to provide a single DNA sample Part E: * Participants 18 years or older * Confirmed diagnosis of CF as determined by the investigator * A total body weight of more than or equal to (\>=) 35 kg * Participants must be heterozygous for F508del with a second CFTR allele carrying a minimal function mutation that is not responsive to ELX/TEZ/IVA therapy * Participants must have a forced expiratory volume in 1 second (FEV1) of greater than or equal to (≥) 40% of predicted normal for age, sex, and height Key Exclusion Criteria: Parts A-D: * History of febrile illness or other acute illness within 14 days before the first dose of study drug * Any condition possibly affecting drug absorption Part E: * An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug * History of solid organ or hematological transplantation * History of clinically significant cirrhosis with or without portal hypertension * Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/Exclusion criteria will apply.

Locations (12)

Joe DiMaggio Cycstic Fibrosis & Pulmonary Center

Hollywood, Florida, United States

AdventHealth Medical Group Pulmonology at Orlando Ridgewood

Orlando, Florida, United States

Altasciences Clinical Kansas

Overland Park, Kansas, United States

Outcomes

Primary Outcomes

Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 67)

Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)

Part D: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 80)

Part E: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: From Signing of Informed Consent Form (ICF) up to End of Study (Up to Day 111)

Part C: Maximum Observed Concentration (Cmax) of VX-828 in Plasma in the Absence and Presence of Itraconazole

Time frame: From Day 1 up to Day 71

Part C: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma in the Absence and Presence of Itraconazole

Time frame: From Day 1 up to Day 71

Part C: Maximum Observed Concentration (Cmax) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA

Time frame: From Day 1 up to Day 30

Part C: Area Under the Concentration Versus Time Curve (AUC) of Midazolam in Plasma in the Absence and Presence of VX-828/TEZ/D-IVA

Time frame: From Day 1 up to Day 30

Secondary Outcomes

Data from ClinicalTrials.gov

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Part A: Maximum Observed Concentration (Cmax) of VX-828 in Plasma

Time frame: From Day 1 up to Day 67

Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-828 in Plasma

Time frame: From Day 1 up to Day 67

Part B: Maximum Observed Concentration (Cmax) of VX-828 at Day 28 in Plasma

Time frame: From Day 1 up to Day 80

Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-828 at Day 28 in Plasma

Time frame: From Day 1 up to Day 80

Part C: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: From Signing of Informed Consent Form (ICF) up to Safety Follow Up (Up to Day 82)

Part D: Maximum Observed Concentration (Cmax) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma

Time frame: Day 28

Part D: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ and D-IVA and their Metabolites at Day 28 in Plasma

Time frame: Day 28

Part E: Maximum Observed Concentration (Cmax) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma

Time frame: Day 1 and Day 28

Part E: Area Under the Concentration Versus Time Curve (AUC) of VX-828, TEZ, and D-IVA and their Metabolites in Plasma

Time frame: Day 28

Part E: Pre-dose Plasma Concentration (Ctrough) of VX-828, TEZ, D-IVA and its Metabolites

Time frame: Pre-dose at Day 4, Day 8, Day 15, Day 22, Day 35, Day 49, Day 63, Day 80

Part E: Absolute Change in Sweat Chloride

Time frame: From Baseline and At Day 28