Pharmacokinetics and Safety Assessment of VX-121/Tezacaftor/Deutivacaftor in Participants With Moderate Hepatic Impairment

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics (PK) and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in participants with moderate hepatic impairment and in matched 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, Open-label Study to Assess the Pharmacokinetics and Safety of a Single Dose of VX-121/Tezacaftor/Deutivacaftor in Subjects With Moderate Hepatic Impairment and in Matched Healthy Subjects

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-121/TEZ/D-IVA


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Cohort 1: Participants with Moderate Hepatic Impairment Participants will satisfy the criteria for moderate hepatic impairment defined as a Child-Pugh total score of 7 to 9 points at the screening visit Participants will have chronic (≥6 months) documented liver disease Cohort 2: Matched Healthy Participants Participants will be matched during screening to participants with hepatic impairment for cigarette smoking habit, age, sex, and weight Key Exclusion Criteria: Cohort 1: Participants with Moderate Hepatic Impairment History of febrile illness or other acute illness History of solid organ or bone marrow transplantation History or presence of severe hepatic encephalopathy (Grade >2) Any condition possibly affecting drug absorption Severe portal hypertension Significant renal dysfunction (creatinine clearance <50 milliliter per minute [mL/min] ) estimated according to the method of Cockcroft and Gault at the screening Visit or Day-1 Cohort 2: Matched Healthy Participants History of febrile illness or other acute illness 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: 70 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Moderate Hepatic Impairment<br>Participants with moderate hepatic impairment will receive single dose of VX-121/TEZ/D-IVA . | Drug: VX-121/TEZ/D-IVA<br>* Fixed-dose combination tablets for oral administration.<br>* Other names: VX-121/tezacaftor/deutivacaftor;|
| Experimental: Cohort 2: Matched Healthy Participants<br>Healthy participants will receive single dose of VX-121/TEZ/D-IVA. | Drug: VX-121/TEZ/D-IVA<br>* Fixed-dose combination tablets for oral administration.<br>* Other names: VX-121/tezacaftor/deutivacaftor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of VX-121, TEZ, D-IVA, and Relevant Metabolites |  | Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-dose up to Day 13 | 
| Area Under the Concentration Versus Time Curve (AUC) of VX-121,TEZ, D-IVA, and Relevant Metabolites |  | Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-Dose up to Day 13 | 
| Fraction Unbound (fu) for VX-121 and D-IVA in Plasma |  | Cohorts 1 and 2: Pre-dose up to Day 2 | 
| Unbound Maximum Observed Concentration (Cmax ub) for VX-121 and D-IVA |  | Cohorts 1 and 2: Pre-dose up to Day 2 | 
| Unbound Area Under the Concentration Versus Time Curve (AUC ub) of VX-121 and D-IVA |  | Cohorts 1 and 2: Pre-dose up to Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Cohort 1: Day 1 up to Day 32; Cohort 2: Day 1 up to Day 17 |