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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05437120
• Other study ID #: VX21-121-008
• Status: Completed
• Phase: Phase 1
• Start date: July 22, 2022
• Est. completion date: March 16, 2023

Study information

• Verified date: March 2023
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 16, 2023
• Est. primary completion date: March 16, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis

Intervention

Drug:
• VX-121/TEZ/D-IVA
Fixed-dose combination tablets for oral administration.

Locations

Country	Name	City	State
United States	Clinical Pharmacology of Miami, LLC	Miami	Florida
United States	GCP Research	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Fraction Unbound (fu) for VX-121 and D-IVA in Plasma		Cohorts 1 and 2: Pre-dose up to Day 2
Primary	Unbound Maximum Observed Concentration (Cmax ub) for VX-121 and D-IVA		Cohorts 1 and 2: Pre-dose up to Day 2
Primary	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	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