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

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03713242
• Other study ID #: ID-078-112
• Status: Completed
• Phase: Phase 1
• Start date: February 26, 2018
• Est. completion date: February 27, 2020

Study information

• Verified date: July 2020
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT03686995

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 27, 2020
• Est. primary completion date: February 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• ACT-541468 25 mg
Administered as a tablet.
• ACT-541468 25 mg (or 10 mg depending on interim results)
Administered as a tablet.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma pharmacokinetics: AUC(0-t)		At various timepoints (duration: up to 4 days)
Other	Plasma pharmacokinetics: AUC(0-inf)		At various timepoints (duration: up to 4 days)
Other	Plasma pharmacokinetics: AUC(0-24)		At various timepoints (duration: up to 4 days)
Other	Plasma pharmacokinetics: Cmax		At various timepoints (duration: up to 4 days)
Other	Plasma pharmacokinetics: Tmax		At various timepoints (duration: up to 4 days)
Other	Plasma pharmacokinetics: T1/2		At various timepoints (duration: up to 4 days)
Other	Plasma pharmacokinetics: Cu/C (extent of plasma protein binding)		At various timepoints (duration: up to 4 days)
Primary	Treatment-emergent adverse events (AEs)		From study treatment administration up to EOS (duration: up to 4 days)
Primary	Treatment-emergent serious adverse events (SAEs)		From study treatment administration up to EOS (duration: up to 4 days)