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

Phase 1

Completed

• Conditions: Hepatic Impairment
• Interventions: Drug: ACT-541468 25 mg; Drug: ACT-541468 25 mg (or 10 mg depending on interim results)

• Registration Number: NCT03713242
• Lead Sponsor: Idorsia Pharmaceuticals Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-26
• Study First Submitted: 2018-10-18
• Study First Submitted QC: 2018-10-18
• Study First Posted: 2018-10-19
• Primary Completion: 2020-02-27
• Study Completion: 2020-02-27
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-01
• Last Update Posted: 2020-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group A: ACT-541468 in subjects with mild hepatic impairment	ACT-541468 25 mg	Single oral dose administered on Day 1.
Group B: ACT-541468 in subj. with moderate hepatic impairment	ACT-541468 25 mg (or 10 mg depending on interim results)	Single oral dose administered on Day 1.
Group C: ACT-541468 in subjects with severe hepatic impairment	ACT-541468 25 mg (or 10 mg depending on interim results)	Single oral dose administered on Day 1.
Group D: ACT-541468 in healthy subjects.	ACT-541468 25 mg (or 10 mg depending on interim results)	Single oral dose administered on Day 1.

Primary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, Switzerland