A Study to Evaluate ACT-132577 in Healthy Subjects and in People With Severe Kidney Disease

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

Official Title
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A Single-center, Open Label, Single-dose Study to Investigate the Effect of Severe Renal Impairment on the Pharmacokinetics of ACT-132577

Conditions
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Severe Renal Impairment, Healthy Subjects

Intervention / Treatment
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* Drug: ACT-132577


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-132577 (50 mg)<br>8 healthy subjects and 8 subjects with severe renal function impairment will receive a single oral dose of 50 mg ACT-132577 administered as capsule following an overnight fast | Drug: ACT-132577<br>* Capsule<br>* Other names: Aprocitentan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) of ACT-132577 | Cmax of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles | From baseline to up to 16 days | 
| Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of ACT-132577 | AUC(0-T) of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles | From baseline to up to 16 days | 
| Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)] | AUC(0-inf) of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles | From baseline to up to 16 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach Cmax (tmax) of ACT-132577 | tmax of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles | From baseline to up to 16 days | 
| Terminal half-life [t(1/2)] | t1/2 of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles | From baseline to up to 16 days | 
| Incidence of treatment-emergent adverse events | The percentage of subjects with treatment-emergent adverse events will be reported | From baseline to up to 16 days | 
| Incidence of adverse events leading to premature discontinuation of study treatment | The number of subjects who prematurely discontinued the study treatment due to an adverse event will be reported | From baseline to up to 16 days | 
| Incidence of any clinical relevant findings in ECG variables | The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported | From baseline to up to 16 days |