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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: VX-121/TEZ/D-IVA

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.).

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014-3616
      • Clinical Pharmacology of Miami, LLC
    • Saint Petersburg, Florida, United States, 33705
      • GCP Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Moderate Hepatic Impairment; Participants with moderate hepatic impairment will receive single dose of VX-121/TEZ/D-IVA .	Drug: VX-121/TEZ/D-IVA; Fixed-dose combination tablets for oral administration.; Other Names: VX-121/VX-661/CTP-656; VX-121/VX-661/VX-561; VX-121/tezacaftor/deutivacaftor
Experimental: Cohort 2: Matched Healthy Participants; Healthy participants will receive single dose of VX-121/TEZ/D-IVA.	Drug: VX-121/TEZ/D-IVA; Fixed-dose combination tablets for oral administration.; Other Names: VX-121/VX-661/CTP-656; VX-121/VX-661/VX-561; VX-121/tezacaftor/deutivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2022
• Primary Completion (Actual): March 16, 2023
• Study Completion (Actual): March 16, 2023

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis
• Other Study ID Numbers: VX21-121-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No