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

Primary Purpose

Severe Renal Impairment, Healthy Subjects

Status

Completed

Phase

Phase 1

Locations

Czechia

Study Type

Interventional

Intervention

ACT-132577

About this trial

This is an interventional other trial for Severe Renal Impairment

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

CEPHA

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ACT-132577 (50 mg)

Arm Description

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

Outcomes

Primary Outcome Measures

Maximum plasma concentration (Cmax) of ACT-132577

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

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)]

AUC(0-inf) of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles

Secondary Outcome Measures

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

Terminal half-life [t(1/2)]

t1/2 of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles

Incidence of treatment-emergent adverse events

The percentage of subjects with treatment-emergent adverse events will be reported

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

Incidence of any clinical relevant findings in ECG variables

The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported

Full Information

NCT ID

NCT03165071

First Posted

May 23, 2017

Last Updated

November 22, 2022

Sponsor

Idorsia Pharmaceuticals Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03165071

Brief Title

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

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

June 3, 2017 (Actual)

Primary Completion Date

October 27, 2017 (Actual)

Study Completion Date

October 27, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Idorsia Pharmaceuticals Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Renal Impairment, Healthy Subjects

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ACT-132577 (50 mg)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

ACT-132577

Other Intervention Name(s)

Aprocitentan

Intervention Description

Capsule

Primary Outcome Measure Information:

Title

Maximum plasma concentration (Cmax) of ACT-132577

Description

Cmax of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles

Time Frame

From baseline to up to 16 days

Title

Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of ACT-132577

Description

AUC(0-T) of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles

Time Frame

From baseline to up to 16 days

Title

Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)]

Description

AUC(0-inf) of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles

Time Frame

From baseline to up to 16 days

Secondary Outcome Measure Information:

Title

Time to reach Cmax (tmax) of ACT-132577

Description

tmax of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles

Time Frame

From baseline to up to 16 days

Title

Terminal half-life [t(1/2)]

Description

t1/2 of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profiles

Time Frame

From baseline to up to 16 days

Title

Incidence of treatment-emergent adverse events

Description

The percentage of subjects with treatment-emergent adverse events will be reported

Time Frame

From baseline to up to 16 days

Title

Incidence of adverse events leading to premature discontinuation of study treatment

Description

The number of subjects who prematurely discontinued the study treatment due to an adverse event will be reported

Time Frame

From baseline to up to 16 days

Title

Incidence of any clinical relevant findings in ECG variables

Description

The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported

Time Frame

From baseline to up to 16 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Idorsia Pharmaceuticals Ltd.

Official's Role

Study Director

Facility Information:

Facility Name

CEPHA

City

Plzen

ZIP/Postal Code

32300

Country

Czechia

12. IPD Sharing Statement

Citations:

PubMed Identifier

31435905

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.

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

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