Hepatic Impairment, Healthy Subjects
Conditions
Keywords
Liver Diseases
Brief summary
This is a prospective, open-label, single-dose, Phase 1 study, to assess the effect of moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics of aprocitentan (ACT-132577).
Interventions
DRUGAprocitentan
A single oral dose of 25 mg.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Healthy subjects will be matched to subjects with moderate hepatic impairment
Eligibility
Sex/Gender
ALL
Age
30 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent in a language understandable to the subject prior to any study-mandated procedure. * Women of childbearing potential (WoCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1 and must agree to use highly effective methods of contraception from screening up to 30 days after study treatment. * A Women of non-childbearing potential (WoNCBP) must meet one of the following criteria: * Previous bilateral salpingectomy, salpingo-oophorectomy or hysterectomy. * Premature ovarian failure confirmed by a specialist gynecologist. * Post-menopausal, defined as 12 consecutive months with amenorrhea prior to screening without alternative medical cause and confirmed with a follicle stimulating hormone test. * Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening. * Normal renal function confirmed by a creatinine clearance at screening according to Cockcroft and Gault adjusted to age. * Additional principal inclusion criteria for subjects with moderate hepatic impairment (Group 1) * Moderate hepatic function impairment due to liver cirrhosis defined as a score of 7-9 (inclusive) according to the Child-Pugh classification. * Systolic blood pressure 95 to 160 mmHg, diastolic blood pressure 60 to 95 mmHg, and pulse rate 50 to 100 bpm (inclusive), measured on the same arm, after 5 minutes in the supine position at screening and on Day 1 pre-dose. * International normalized ratio equal or less than 2.5 at screening. * Stable concomitant medications for at least 3 weeks prior to screening and up to Day 1 and expected to be stable during the conduct of the study. * Additional principal inclusion criteria for healthy subjects (Group 2) * Healthy on the basis of medical history, physical examination, cardiovascular assessments, and clinical laboratory tests.
Exclusion criteria
* Pregnant or lactating women. * Previous exposure to aprocitentan and/or macitentan. * Known hypersensitivity to any excipients of the drug formulation. * Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. * Any signs or symptoms of active, ongoing infection judged to be clinically relevant by the investigator (special attention should be given to COVID-19, e.g., fever, dry cough, dyspnea, sore throat, or fatigue). * Subjects must adhere to the clinical site's house rules, which include, amongst others, polymerase chain reaction testing for SARS-CoV-2 at screening and admission. * Legal incapacity or limited legal capacity at screening. * Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The maximum plasma concentration (Cmax) of aprocitentan | Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14. |
| Area under the plasma concentration-time curves (AUC0-t) of aprocitentan | Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14. |
| Area under the plasma concentration-time curve to infinity (AUC0 to inf) of aprocitentan | Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 14. |
Secondary
| Measure | Time frame |
|---|---|
| Treatment-emergent Adverse Events | From study treatment administration on Day 1 up to last assessment on End of Study (Day 15) |
Countries
Germany, Poland
Outcome results
None listed