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

Sponsor

Vertex Pharmaceuticals Incorporated (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05560464

Collaborator

(none)

Enrollment

Locations

Arms

6.5

Anticipated Duration (Months)

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: VX-548	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

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

Actual Study Start Date :

Oct 14, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Mild Hepatic Impairment Participants will receive multiple doses of VX-548 every 12 hours (q12h) from Day 1 through Day 14.	Drug: VX-548 Tablets for oral administration.
Experimental: Cohort 2: Matched Healthy Participants Healthy participants matched to cohort 1 will receive multiple doses of VX-548 q12h from Day 1 through Day 14.	Drug: VX-548 Tablets for oral administration.
Experimental: Cohort 3: Moderate Hepatic Impairment Participants will receive multiple doses of VX-548 q12h from Day 1 through Day 14.	Drug: VX-548 Tablets for oral administration.
Experimental: Cohort 4: Matched Healthy Participants Healthy participants matched to cohort 3 will receive multiple doses of VX-548 q12h from Day 1 through Day 14.	Drug: VX-548 Tablets for oral administration.

Outcome Measures

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of VX-548 [Day 1 to Day 31]
Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548 [Day 1 to Day 31]
Time Taken for VX-548 to Reach Maximum Concentration (tmax) [Day 1 to Day 31]
Time Required for Plasma Concentration of VX-548 to Reduce to Half (t1/2) [Day 1 to Day 31]
Apparent Volume of Distribution of VX-548 (Vz/F) [Day 1 to Day 31]
Apparent Clearance of VX-548 (CL/F) [Day 1 to Day 31]
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 Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of VX-548 Metabolite [Day 1 to Day 31]
Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548 Metabolite [Day 1 to Day 31]
Time Taken for VX-548 metabolite to Reach Maximum Concentration (tmax) [Day 1 to Day 31]
Time Required for Plasma Concentration of VX-548 Metabolite to Reduce to Half (t1/2) [Day 1 to Day 31]
Apparent Volume of Distribution of VX-548 Metabolite (Vz/F) [Day 1 to Day 31]
Apparent Clearance of VX-548 Metabolite (CL/F) [Day 1 to Day 31]
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]
Fraction Unbound (fu) for VX-548 and its Metabolite in Plasma [Day 14: Up to 24 hours Post-dose]
Unbound Area Under the Concentration Versus Time Curve of VX-548 and its Metabolite [Day 14: Up to 24 hours Post-dose]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Division of Clinical Pharmacology, University of Miami	Miami	Florida	United States	33136
2	Orlando Clinical Research Center	Orlando	Oklahoma	United States	32809

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Vertex Pharmaceuticals Incorporated

ClinicalTrials.gov Identifier:

NCT05560464

Other Study ID Numbers:

VX21-548-007

First Posted:

Sep 29, 2022

Last Update Posted:

Nov 8, 2022

Last Verified:

Sep 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Study Results

No Results Posted as of Nov 8, 2022