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

NCT05560464 | Completed Phase 1 FDA Drug

• 1 other identifier: VX21-548-007
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Pain

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• 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

Study Arms (4)

Cohort 1: Mild Hepatic Impairment

EXPERIMENTAL

Participants will receive multiple doses of VX-548 every 12 hours (q12h) from Day 1 through Day 14.

Drug: VX-548

Cohort 2: Matched Healthy Participants

EXPERIMENTAL

Healthy participants matched to cohort 1 will receive multiple doses of VX-548 q12h from Day 1 through Day 14.

Drug: VX-548

Cohort 3: Moderate Hepatic Impairment

EXPERIMENTAL

Participants will receive multiple doses of VX-548 q12h from Day 1 through Day 14.

Drug: VX-548

Cohort 4: Matched Healthy Participants

EXPERIMENTAL

Healthy participants matched to cohort 3 will receive multiple doses of VX-548 q12h from Day 1 through Day 14.

Drug: VX-548

Interventions

VX-548 DRUG

Tablets for oral administration.

Also known as: Suzetrigine

Cohort 1: Mild Hepatic Impairment; Cohort 2: Matched Healthy Participants; Cohort 3: Moderate Hepatic Impairment; Cohort 4: Matched Healthy Participants

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (2)

Division of Clinical Pharmacology, University of Miami

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Oklahoma, 32809, United States

Location

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: September 29, 2022
• Study Start: October 14, 2022
• Primary Completion: July 24, 2023
• Study Completion: July 24, 2023
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)