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

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03165071
• Other study ID #: AC-080-105
• Secondary ID: 2016-005077-12
• Status: Completed
• Phase: Phase 1
• Start date: June 3, 2017
• Est. completion date: October 27, 2017

Study information

• Verified date: November 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 27, 2017
• Est. primary completion date: October 27, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Subjects
• Renal Insufficiency
• Severe Renal Impairment

Intervention

Drug:
• ACT-132577
Capsule

Locations

Country	Name	City	State
Czechia	CEPHA	Plzen

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Czechia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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