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

Phase 1
Completed
Conditions
Cystic Fibrosis
Interventions
Registration Number
NCT05437120
Lead Sponsor
Vertex Pharmaceuticals Incorporated
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.).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 1: Moderate Hepatic ImpairmentVX-121/TEZ/D-IVAParticipants with moderate hepatic impairment will receive single dose of VX-121/TEZ/D-IVA .
Cohort 2: Matched Healthy ParticipantsVX-121/TEZ/D-IVAHealthy participants will receive single dose of VX-121/TEZ/D-IVA.
Primary Outcome Measures
NameTimeMethod
Area Under the Concentration Versus Time Curve (AUC) of VX-121,TEZ, D-IVA, and Relevant MetabolitesCohort 1: Pre-dose up to Day 23; Cohort 2: Pre-Dose up to Day 13
Maximum Observed Plasma Concentration (Cmax) of VX-121, TEZ, D-IVA, and Relevant MetabolitesCohort 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 PlasmaCohorts 1 and 2: Pre-dose up to Day 2
Unbound Maximum Observed Concentration (Cmax ub) for VX-121 and D-IVACohorts 1 and 2: Pre-dose up to Day 2
Unbound Area Under the Concentration Versus Time Curve (AUC ub) of VX-121 and D-IVACohorts 1 and 2: Pre-dose up to Day 2
Secondary Outcome Measures
NameTimeMethod
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

Trial Locations

Locations (2)

Clinical Pharmacology of Miami, LLC

🇺🇸

Miami, Florida, United States

GCP Research

🇺🇸

Saint Petersburg, Florida, United States

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