Clinical trial NCT03165071: A Study to Evaluate ACT-132577 in Healthy Subjects and in People With Severe Kidney Disease
Official title: A Single-center, Open Label, Single-dose Study to Investigate the Effect of Severe Renal Impairment on the Pharmacokinetics of ACT-132577
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Severe Renal Impairment
Healthy Subjects
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The primary purpose of this study is to investigate the fate of ACT-132577 in healthy subjects and in people with severe kidney disease


Eligibility criteria: Inclusion Criteria:

ALL SUBJECTS:

* Signed informed consent in the local language prior to any study-mandated procedure;
* Male/female aged 18 to 65 years (inclusive) at screening;
* Body mass index of 18.0 to 32.0 kg/m2 (inclusive) at screening. Body weight at least 50 kg;
* Women of childbearing potential must have a negative serum pregnancy test and use reliable birth controls up to 30 days after the end of study treatment.

HEALTHY SUBJECTS:

* Normal renal function confirmed by the estimated glomerular filtration rate (eGFR) determined at screening;
* Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests.

SEVERE RENAL FUNCTION IMPAIRMENT SUBJECTS:

- Severe renal function impairment is defined by eGFR estimated at screening between 15 mL/min/1.73 m2 and 29 mL/min/1.73 m2 (inclusive).

Exclusion Criteria:

ALL SUBJECTS:

* Pregnant or lactating women;
* Known hypersensitivity to ACT-132577 or drugs of the same class, or any of their excipients;
* Known hypersensitivity or allergy to natural rubber latex;
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

SEVERE RENAL FUNCTION IMPAIRMENT SUBJECTS:

* End-stage renal disease that requires dialysis;
* Hemoglobin concentration \< 9 g/dL;
* History of severe renal stenosis;
* Serum potassium concentration \> 5.5 mmol/L;
* Presence of severe cardiac disease;
* History of clinically relevant bleeding disorder;
* Presence of any organ disorder, with the exception of renal function impairment, or use of any medication which might interfere with the pharmacokinetics of ACT-132577;
* Known life-threatening disease with a life expectancy of less than 1 year;
* Presence of unstable diabetes mellitus.

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of ACT-132577
timeFrame: From baseline to up to 16 days
measure: Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of ACT-132577
timeFrame: From baseline to up to 16 days
measure: Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)]
timeFrame: From baseline to up to 16 days
Secondary outcomes:
measure: Time to reach Cmax (tmax) of ACT-132577
timeFrame: From baseline to up to 16 days
measure: Terminal half-life [t(1/2)]
timeFrame: From baseline to up to 16 days
measure: Incidence of treatment-emergent adverse events
timeFrame: From baseline to up to 16 days
measure: Incidence of adverse events leading to premature discontinuation of study treatment
timeFrame: From baseline to up to 16 days
measure: Incidence of any clinical relevant findings in ECG variables
timeFrame: From baseline to up to 16 days
Other outcomes:
Locations:
city: Plzen
country: Czechia
facility: CEPHA
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Sidharta PN, Ulc I, Dingemanse J. Single-Dose Pharmacokinetics and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Subjects with Severe Renal Function Impairment. Clin Drug Investig. 2019 Nov;39(11):1117-1123. doi: 10.1007/s40261-019-00837-x.