Hepatic Impairment
Conditions
Brief summary
This is a prospective, single-center, open-label, single-dose, Phase 1 study, to assess the effect of mild, moderate, and severe hepatic impairment due to liver cirrhosis on the pharmacokinetics of ACT-541468.
Interventions
DRUGACT-541468 25 mg
Administered as a tablet.
DRUGACT-541468 25 mg (or 10 mg depending on interim results)
Administered as a tablet.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
prospective, single-center, open-label, single-dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent prior to any study-mandated procedure. * Male and female subjects aged between 18 and 75 years (inclusive) at screening. * Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use (from screening, during the entire study, and for at least one month after last study treatment intake) a highly effective method of contraception, be sexually inactive, or have a vasectomized partner. * Women of non-childbearing potential. * Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening. * For healthy subjects: Normal renal function confirmed by a creatinine clearance at screening according to Cockroft and Gault adjusted to age of: 1. ≥ 80 mL/min/1.73 m2 for subjects ≤ 50 years of age. 2. ≥ 70 mL/min/1.73 m2 for subjects 51-60 years of age. 3. ≥ 60 mL/min/1.73 m2 for subjects 61-75 years of age. * For subjects with hepatic impairment: Degree of liver function impairment due to liver cirrhosis according to the Child-Pugh classification: 1. Group A: Mild hepatic impairment, Child-Pugh score 5-6. 2. Group B: Moderate hepatic impairment, Child-Pugh score 7-9. 3. Group C: Severe hepatic impairment, Child-Pugh score 10-15.
Exclusion criteria
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. * For subjects with hepatic impairment: History of major medical or surgical disorders, which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment except for those related to liver cirrhosis (appendectomy and herniotomy allowed, cholecystectomy not allowed). * For healthy subjects: 1. History of alcoholism or drug abuse within the 3-year period prior to screening. 2. Relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment-emergent adverse events (AEs) | From study treatment administration up to EOS (duration: up to 4 days) |
| Treatment-emergent serious adverse events (SAEs) | From study treatment administration up to EOS (duration: up to 4 days) |
Other
| Measure | Time frame |
|---|---|
| Plasma pharmacokinetics: AUC(0-24) | At various timepoints (duration: up to 4 days) |
| Plasma pharmacokinetics: Cmax | At various timepoints (duration: up to 4 days) |
| Plasma pharmacokinetics: AUC(0-t) | At various timepoints (duration: up to 4 days) |
| Plasma pharmacokinetics: T1/2 | At various timepoints (duration: up to 4 days) |
| Plasma pharmacokinetics: Cu/C (extent of plasma protein binding) | At various timepoints (duration: up to 4 days) |
| Plasma pharmacokinetics: Tmax | At various timepoints (duration: up to 4 days) |
| Plasma pharmacokinetics: AUC(0-inf) | At various timepoints (duration: up to 4 days) |
Countries
Switzerland
Outcome results
None listed