Clinical trial NCT03713242: A Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-10-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: prospective, single-center, open-label, single-dose
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Treatment-emergent adverse events (AEs)
timeFrame: From study treatment administration up to EOS (duration: up to 4 days)
measure: Treatment-emergent serious adverse events (SAEs)
timeFrame: From study treatment administration up to EOS (duration: up to 4 days)
Secondary outcomes:
Other outcomes:
measure: Plasma pharmacokinetics: AUC(0-t)
timeFrame: At various timepoints (duration: up to 4 days)
measure: Plasma pharmacokinetics: AUC(0-inf)
timeFrame: At various timepoints (duration: up to 4 days)
measure: Plasma pharmacokinetics: AUC(0-24)
timeFrame: At various timepoints (duration: up to 4 days)
measure: Plasma pharmacokinetics: Cmax
timeFrame: At various timepoints (duration: up to 4 days)
measure: Plasma pharmacokinetics: Tmax
timeFrame: At various timepoints (duration: up to 4 days)
measure: Plasma pharmacokinetics: T1/2
timeFrame: At various timepoints (duration: up to 4 days)
measure: Plasma pharmacokinetics: Cu/C (extent of plasma protein binding)
timeFrame: At various timepoints (duration: up to 4 days)
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.