A Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment

Study Overview
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Brief Summary
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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.

Official Title
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A Single-center, Open-label, Single-dose, Phase 1 Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: ACT-541468 25 mg
* Drug: ACT-541468 25 mg (or 10 mg depending on interim results)


Participation Criteria
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Eligibility Criteria
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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: ≥ 80 mL/min/1.73 m2 for subjects ≤ 50 years of age. ≥ 70 mL/min/1.73 m2 for subjects 51-60 years of age. ≥ 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: Group A: Mild hepatic impairment, Child-Pugh score 5-6. Group B: Moderate hepatic impairment, Child-Pugh score 7-9. 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: History of alcoholism or drug abuse within the 3-year period prior to screening. Relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: prospective, single-center, open-label, single-dose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: ACT-541468 in subjects with mild hepatic impairment<br>Single oral dose administered on Day 1. | Drug: ACT-541468 25 mg<br>* Administered as a tablet.<br>|
| Experimental: Group B: ACT-541468 in subj. with moderate hepatic impairment<br>Single oral dose administered on Day 1. | Drug: ACT-541468 25 mg (or 10 mg depending on interim results)<br>* Administered as a tablet.<br>|
| Experimental: Group C: ACT-541468 in subjects with severe hepatic impairment<br>Single oral dose administered on Day 1. | Drug: ACT-541468 25 mg (or 10 mg depending on interim results)<br>* Administered as a tablet.<br>|
| Experimental: Group D: ACT-541468 in healthy subjects.<br>Single oral dose administered on Day 1. | Drug: ACT-541468 25 mg (or 10 mg depending on interim results)<br>* Administered as a tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) |