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

NCT03713242 | Completed Phase 1 FDA Drug

• 1 other identifier: ID-078-112
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Plasma pharmacokinetics: AUC(0-t)

  At various timepoints (duration: up to 4 days)

• Plasma pharmacokinetics: AUC(0-inf)

  At various timepoints (duration: up to 4 days)

• Plasma pharmacokinetics: AUC(0-24)

  At various timepoints (duration: up to 4 days)

Study Arms (4)

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

EXPERIMENTAL

Single oral dose administered on Day 1.

Drug: ACT-541468 25 mg

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

EXPERIMENTAL

Single oral dose administered on Day 1.

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

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

EXPERIMENTAL

Single oral dose administered on Day 1.

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

Group D: ACT-541468 in healthy subjects.

EXPERIMENTAL

Single oral dose administered on Day 1.

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

Interventions

ACT-541468 25 mg DRUG

Administered as a tablet.

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

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

Administered as a tablet.

Group B: ACT-541468 in subj. with moderate hepatic impairment; Group C: ACT-541468 in subjects with severe hepatic impairment; Group D: ACT-541468 in healthy subjects.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 34002356 DERIVED

MeSH Terms

Interventions

daridorexant

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: prospective, single-center, open-label, single-dose

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 19, 2018
• Study Start: February 26, 2018
• Primary Completion: February 27, 2020
• Study Completion: February 27, 2020
• Last Updated: July 2, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)