Pain
Conditions
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.).
Interventions
DRUGVX-548
Tablets for oral administration.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion 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/
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
United States
Outcome results
None listed