Back to resultsPharmacokinetics and Safety Assessment of VX-121/Tezacaftor/Deutivacaftor in Participants With Moderate Hepatic Impairment
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VX-121/TEZ/D-IVA
Sponsored by
About this trial
This is an interventional basic science trial for Cystic Fibrosis
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.
Sites / Locations
- Clinical Pharmacology of Miami, LLC
- GCP Research
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1: Moderate Hepatic Impairment
Cohort 2: Matched Healthy Participants
Arm Description
Participants with moderate hepatic impairment will receive single dose of VX-121/TEZ/D-IVA .
Healthy participants will receive single dose of VX-121/TEZ/D-IVA.
Outcomes
Primary Outcome Measures
Maximum Observed Plasma Concentration (Cmax) of VX-121, TEZ, D-IVA, and Relevant Metabolites
Area Under the Concentration Versus Time Curve (AUC) of VX-121,TEZ, D-IVA, and Relevant Metabolites
Fraction Unbound (fu) for VX-121 and D-IVA in Plasma
Unbound Maximum Observed Concentration (Cmax ub) for VX-121 and D-IVA
Unbound Area Under the Concentration Versus Time Curve (AUC ub) of VX-121 and D-IVA
Secondary Outcome Measures
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Full Information
NCT ID
NCT05437120
First Posted
June 23, 2022
Last Updated
March 29, 2023
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT05437120
Brief Title
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
July 22, 2022 (Actual)
Primary Completion Date
March 16, 2023 (Actual)
Study Completion Date
March 16, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Moderate Hepatic Impairment
Arm Type
Experimental
Arm Description
Participants with moderate hepatic impairment will receive single dose of VX-121/TEZ/D-IVA .
Arm Title
Cohort 2: Matched Healthy Participants
Arm Type
Experimental
Arm Description
Healthy participants will receive single dose of VX-121/TEZ/D-IVA.
Intervention Type
Drug
Intervention Name(s)
VX-121/TEZ/D-IVA
Other Intervention Name(s)
VX-121/VX-661/VX-561, VX-121/VX-661/CTP-656, VX-121/tezacaftor/deutivacaftor
Intervention Description
Fixed-dose combination tablets for oral administration.
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of VX-121, TEZ, D-IVA, and Relevant Metabolites
Time Frame
Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-dose up to Day 13
Title
Area Under the Concentration Versus Time Curve (AUC) of VX-121,TEZ, D-IVA, and Relevant Metabolites
Time Frame
Cohort 1: Pre-dose up to Day 23; Cohort 2: Pre-Dose up to Day 13
Title
Fraction Unbound (fu) for VX-121 and D-IVA in Plasma
Time Frame
Cohorts 1 and 2: Pre-dose up to Day 2
Title
Unbound Maximum Observed Concentration (Cmax ub) for VX-121 and D-IVA
Time Frame
Cohorts 1 and 2: Pre-dose up to Day 2
Title
Unbound Area Under the Concentration Versus Time Curve (AUC ub) of VX-121 and D-IVA
Time Frame
Cohorts 1 and 2: Pre-dose up to Day 2
Secondary Outcome Measure Information:
Title
Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Cohort 1: Day 1 up to Day 32; Cohort 2: Day 1 up to Day 17
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
Clinical Pharmacology of Miami, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33014-3616
Country
United States
Facility Name
GCP Research
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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
Learn more about this trial
Pharmacokinetics and Safety Assessment of VX-121/Tezacaftor/Deutivacaftor in Participants With Moderate Hepatic Impairment
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