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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Severe Renal Impairment
• Intervention / Treatment: Drug: ACT-132577

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Plzen, Czechia, 32300
    • CEPHA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACT-132577 (50 mg); 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; Capsule; Other Names: Aprocitentan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2017
• Primary Completion (Actual): October 27, 2017
• Study Completion (Actual): October 27, 2017

Study Registration Dates

• First Submitted: May 23, 2017
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (Actual): May 24, 2017

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: AC-080-105; 2016-005077-12 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No