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

NCT ID: NCT03713242

Last Updated: 2020-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-26
• Study Completion Date: 2020-02-27

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.

Conditions

Hepatic Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Group A: ACT-541468 in subjects with mild hepatic impairment

Single oral dose administered on Day 1.

Group Type: EXPERIMENTAL

ACT-541468 25 mg

Intervention Type: DRUG

Administered as a tablet.

Group B: ACT-541468 in subj. with moderate hepatic impairment

Single oral dose administered on Day 1.

Group Type: EXPERIMENTAL

ACT-541468 25 mg (or 10 mg depending on interim results)

Intervention Type: DRUG

Administered as a tablet.

Group C: ACT-541468 in subjects with severe hepatic impairment

Single oral dose administered on Day 1.

Group Type: EXPERIMENTAL

ACT-541468 25 mg (or 10 mg depending on interim results)

Intervention Type: DRUG

Administered as a tablet.

Group D: ACT-541468 in healthy subjects.

Single oral dose administered on Day 1.

Group Type: EXPERIMENTAL

ACT-541468 25 mg (or 10 mg depending on interim results)

Intervention Type: DRUG

Administered as a tablet.

Interventions

ACT-541468 25 mg

Administered as a tablet.

Intervention Type: DRUG

ACT-541468 25 mg (or 10 mg depending on interim results)

Administered as a tablet.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Idorsia Pharmaceuticals Ltd.

Locations

University Hospital Basel

Basel, , Switzerland

Countries

Switzerland

References

Berger B, Dingemanse J, Sabattini G, Delahaye S, Duthaler U, Muehlan C, Krahenbuhl S. Effect of Liver Cirrhosis on the Pharmacokinetics, Metabolism, and Tolerability of Daridorexant, A Novel Dual Orexin Receptor Antagonist. Clin Pharmacokinet. 2021 Oct;60(10):1349-1360. doi: 10.1007/s40262-021-01028-8. Epub 2021 May 18.

Reference Type: DERIVED

PMID: 34002356 (View on PubMed)

Other Identifiers

ID-078-112

Identifier Type: -

Identifier Source: org_study_id

NCT03686995

Identifier Type: -

Identifier Source: nct_alias