Clinical trial NCT05560464: Evaluation of the Pharmacokinetics and Safety of VX-548 in Participants With Mild or Moderate Hepatic Impairment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pain
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2022-09-29
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.).

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of VX-548
timeFrame: Day 1 to Day 31
measure: Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548
timeFrame: Day 1 to Day 31
measure: Time Taken for VX-548 to Reach Maximum Concentration (tmax)
timeFrame: Day 1 to Day 31
measure: Time Required for Plasma Concentration of VX-548 to Reduce to Half (t1/2)
timeFrame: Day 1 to Day 31
measure: Apparent Volume of Distribution of VX-548 (Vz/F)
timeFrame: Day 1 to Day 31
measure: Apparent Clearance of VX-548 (CL/F)
timeFrame: Day 1 to Day 31
measure: Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to the Last Measured Concentration (AUC0-last) of VX-548
timeFrame: Day 1 to Day 31
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of VX-548 Metabolite
timeFrame: Day 1 to Day 31
measure: Area Under the Plasma Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-548 Metabolite
timeFrame: Day 1 to Day 31
measure: Time Taken for VX-548 metabolite to Reach Maximum Concentration (tmax)
timeFrame: Day 1 to Day 31
measure: Time Required for Plasma Concentration of VX-548 Metabolite to Reduce to Half (t1/2)
timeFrame: Day 1 to Day 31
measure: Apparent Volume of Distribution of VX-548 Metabolite (Vz/F)
timeFrame: Day 1 to Day 31
measure: Apparent Clearance of VX-548 Metabolite (CL/F)
timeFrame: Day 1 to Day 31
measure: Area Under the Concentration Versus Time Curve From the Time of Dosing Extrapolated to the Last Measured Concentration (AUC0-last) of VX-548 Metabolite
timeFrame: Day 1 to Day 31
measure: Fraction Unbound (fu) for VX-548 and its Metabolite in Plasma
timeFrame: Day 14: Up to 24 hours Post-dose
measure: Unbound Area Under the Concentration Versus Time Curve of VX-548 and its Metabolite
timeFrame: Day 14: Up to 24 hours Post-dose
measure: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to Day 42
Other outcomes:
Locations:
city: Miami
country: United States
facility: Division of Clinical Pharmacology, University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Oklahoma
Study officials:
References: