Healthy, Renal Insufficiency
Conditions
Brief summary
Study of the way the body takes up, distributes, and gets rid of ACT-541468 in subjects with abnormal kidney function compared to healthy subjects
Interventions
DRUGACT-541468
ACT-541468 25 mg; administered orally
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Single-center, open-label, single-dose study
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
General inclusion criteria for all subjects: * Signed informed consent in the local language prior to any study mandated procedure. * Male and female subjects aged 18 to 85 years (inclusive) at screening. * Body mass index (BMI) from 18 to 35 kg/m2 (inclusive) at screening. Body weight at least 50 kg. * Women of childbearing potential: Women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use (during the entire study and 30 days thereafter) a highly effective method of contraception with a failure rate of \< 1% per year. * Women of non-childbearing potential, i.e., postmenopausal, XY genotype, Turner syndrome, uterine agenesis: no contraceptive requirement. Additional inclusion criteria for healthy subjects (Group A): * Normal renal function as confirmed based on Creatinine Clearance (CLcr) by the Cockcroft-Gault equation adjusted for age: \>= 80 mL/min for subjects \<= 50 years of age; \>= 70 mL/min for subjects 51-60 years of age; \>= 60 mL/min for subjects 61-85 years of age; CLcr = (\[140-age(years)\]×weight (kg))/(72×serum creatinine (mg/dL)) (x 0.85 for female subjects) * The CLcr value should be confirmed (± 25%) on Day -1 in case subjects will be dosed more than 10 days after the day of screening. * Hematology, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening. * Each healthy subject must be matched with one subject with severe renal function impairment with regard to age (± 10 years difference allowed), body weight (± 15% difference allowed), and sex, determined by results at screening. Additional inclusion criteria for subjects with severe renal function impairment (Group B) * Severe renal function impairment as confirmed based on CLcr by the Cockcroft-Gault equation: \<30 mL/min, not on dialysis. * The CLcr value should be confirmed (± 25%) on Day -1 since subjects will be dosed more than 10 days after the day of screening. * Hematology, clinical chemistry, coagulation and urinalysis test results consistent with severe renal function impairment at screening. * Physical examination without clinically relevant abnormalities at screening and on Day -1 (except for those related to severe renal function impairment), which would interfere with the objectives of the study. * Stable concomitant medications. General
Exclusion criteria
for all subjects: * Pregnant or lactating women. * Clinically relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal * History of renal and/or liver transplant. * Hepatic cancer, primary biliary cirrhosis or any form of cholestatic disease. * Use of drugs which might interfere with the PK of ACT-541468 (moderate to strong CYP3A4 inhibitors or inducers). * Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC of ACT-541468 from time zero to 24 h after study drug administration (AUC0-inf) | Blood samples for PK analysis will be taken at multiple time points after ACT-541468 administration for a total duration of up to 4 days |
Secondary
| Measure | Time frame |
|---|---|
| Number of subjects with treatment-emergent (serious) adverse events (S)AEs | During treatment with ACT-541468 administration for a total duration of up to 4 days |
Other
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) of ACT-541468 | Blood samples for PK analysis will be taken at multiple time points after ACT-541468 administration for a total duration of up to 4 days | — |
| Time to reach maximum plasma concentration (tmax) of ACT-541468 | Blood samples for PK analysis will be taken at multiple time points after ACT-541468 administration for a total duration of up to 4 days | — |
| Terminal half-life (t½) of ACT-541468 | Blood samples for PK analysis will be taken at multiple time points after ACT-541468 administration for a total duration of up to 4 days | — |
| Extent of plasma protein binding (PPB; in %) | Blood samples for PK analysis will be taken at multiple time points after ACT-541468 administration for a total duration of up to 4 days | PPB % = 100 - (Cu/C×100), with 'Cu' standing for unbound and 'C' for total plasma ACT-541468 concentration. |
Countries
Germany
Outcome results
None listed