Clinical trial NCT05437120: Pharmacokinetics and Safety Assessment of VX-121/Tezacaftor/Deutivacaftor in Participants With Moderate Hepatic Impairment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2022-06-29
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.).

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of VX-121, TEZ, D-IVA, and Relevant Metabolites
timeFrame: Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-dose up to Day 13
measure: Area Under the Concentration Versus Time Curve (AUC) of VX-121,TEZ, D-IVA, and Relevant Metabolites
timeFrame: Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-Dose up to Day 13
measure: Fraction Unbound (fu) for VX-121 and D-IVA in Plasma
timeFrame: Cohorts 1 and 2: Pre-dose up to Day 2
measure: Unbound Maximum Observed Concentration (Cmax ub) for VX-121 and D-IVA
timeFrame: Cohorts 1 and 2: Pre-dose up to Day 2
measure: Unbound Area Under the Concentration Versus Time Curve (AUC ub) of VX-121 and D-IVA
timeFrame: Cohorts 1 and 2: Pre-dose up to Day 2
Secondary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Cohort 1: Day 1 up to Day 32; Cohort 2: Day 1 up to Day 17
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, LLC
state: Florida
city: Saint Petersburg
country: United States
facility: GCP Research
state: Florida
Study officials:
References: