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

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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: VX-548

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): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Division of Clinical Pharmacology, University of Miami
  • Oklahoma
    • Orlando, Oklahoma, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.; Other Names: Suzetrigine
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.; Other Names: Suzetrigine
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.; Other Names: Suzetrigine
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.; Other Names: Suzetrigine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Actual): July 24, 2023
• Study Completion (Actual): July 24, 2023

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: VX21-548-007

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