Evaluation of the Pharmacokinetics and Safety of VX-548 in Participants With Mild or Moderate Hepatic Impairment

Pain Clinical Trial

Official title:

A Phase 1, Open-label Study to Evaluate the Pharmacokinetics and Safety of Multiple Doses of VX-548 in Subjects With Mild or Moderate Hepatic Impairment and in Matched Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05560464
• Other study ID #: VX21-548-007
• Status: Completed
• Phase: Phase 1
• Start date: October 14, 2022
• Est. completion date: July 24, 2023

Study information

• Verified date: March 2024
• 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 and safety of multiple doses of VX-584 in participants with mild or moderate hepatic impairment as compared to matched healthy controls.

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: 36
• Est. completion date: July 24, 2023
• Est. primary completion date: July 24, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

• Cohorts 1 and 3: Participants with Mild or Moderate Hepatic Impairment

• Participants will satisfy the criteria for mild (Cohort 1) and moderate hepatic impairment (Cohort 3) defined as a Child-Pugh total score of 5 to 6 and 7 to 9 points, respectively at the screening visit

• Participants will have chronic (greater than or equal to (=) 6 months) documented liver disease

• Cohorts 2 and 4: Matched Healthy Participants

• Participants will be matched (cohort 2 matched to cohort 1; and cohort 4 matched to cohort 3) during screening to participants with hepatic impairment for age, sex, and weight

Key Exclusion Criteria:

• Cohorts 1 and 3: Participants with Mild or Moderate Hepatic Impairment

• History of febrile illness or other acute illness that has not fully resolved by 14 days before the first dose of study drug

• Severe portal hypertension

• History or presence of severe hepatic encephalopathy (Grade >2)

• Any condition possibly affecting drug absorption

• Significant renal dysfunction (creatinine clearance <60 milliliter per minute [mL/min] ) estimated according to the method of Cockcroft and Gault at the screening Visit or Day-1

• History of solid organ or bone marrow transplantation

• Cohorts 2 and 4: Matched Healthy Participants

• History of febrile illness or other acute illness that has not fully resolved by 14 days before the first dose of study drug

• Any condition possibly affecting drug absorption

Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• VX-548
Tablets for oral administration.

Locations

Country	Name	City	State
United States	Division of Clinical Pharmacology, University of Miami	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Oklahoma

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-548		Day 1 to Day 31
Primary	Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548		Day 1 to Day 31
Primary	Time Taken for VX-548 to Reach Maximum Concentration (tmax)		Day 1 to Day 31
Primary	Time Required for Plasma Concentration of VX-548 to Reduce to Half (t1/2)		Day 1 to Day 31
Primary	Apparent Volume of Distribution of VX-548 (Vz/F)		Day 1 to Day 31
Primary	Apparent Clearance of VX-548 (CL/F)		Day 1 to Day 31
Primary	Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to the Last Measured Concentration (AUC0-last) of VX-548		Day 1 to Day 31
Secondary	Maximum Observed Plasma Concentration (Cmax) of VX-548 Metabolite		Day 1 to Day 31
Secondary	Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548 Metabolite		Day 1 to Day 31
Secondary	Time Taken for VX-548 metabolite to Reach Maximum Concentration (tmax)		Day 1 to Day 31
Secondary	Time Required for Plasma Concentration of VX-548 Metabolite to Reduce to Half (t1/2)		Day 1 to Day 31
Secondary	Apparent Volume of Distribution of VX-548 Metabolite (Vz/F)		Day 1 to Day 31
Secondary	Apparent Clearance of VX-548 Metabolite (CL/F)		Day 1 to Day 31
Secondary	Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to the Last Measured Concentration (AUC0-last) of VX-548 Metabolite		Day 1 to Day 31
Secondary	Fraction Unbound (fu) for VX-548 and its Metabolite in Plasma		Day 14: Up to 24 hours Post-dose
Secondary	Unbound Area Under the Concentration Versus Time Curve of VX-548 and its Metabolite		Day 14: Up to 24 hours Post-dose
Secondary	Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		From Day 1 up to Day 42