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

Phase 1

Completed

• Conditions: Healthy Subjects; Severe Renal Impairment
• Interventions: Drug: ACT-132577

• Registration Number: NCT03165071
• Lead Sponsor: Idorsia Pharmaceuticals Ltd.

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-23
• Study First Submitted QC: 2017-05-23
• Study First Posted: 2017-05-24
• Study Start: 2017-06-03
• Primary Completion: 2017-10-27
• Study Completion: 2017-10-27
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-22
• Last Update Posted: 2022-11-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ACT-132577 (50 mg)	ACT-132577	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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CEPHA; 🇨🇿 Plzen, Czechia