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

NCT03165071 | Completed Phase 1

• 2 other identifiers: AC-080-1052016-005077-12
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Conditions

Severe Renal Impairment; Healthy Subjects

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Time to reach Cmax (tmax) of ACT-132577

  From baseline to up to 16 days

• Terminal half-life [t(1/2)]

  From baseline to up to 16 days

• Incidence of treatment-emergent adverse events

  From baseline to up to 16 days

• Incidence of adverse events leading to premature discontinuation of study treatment

  From baseline to up to 16 days

• Incidence of any clinical relevant findings in ECG variables

  From baseline to up to 16 days

Study Arms (1)

ACT-132577 (50 mg)

EXPERIMENTAL

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

Interventions

ACT-132577 DRUG

Capsule

Also known as: Aprocitentan

ACT-132577 (50 mg)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

CEPHA

Pilsen, 32300, Czechia

Location

Related 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.

  PMID: 31435905 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency

Interventions

aprocitentan

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 24, 2017
• Study Start: June 3, 2017
• Primary Completion: October 27, 2017
• Study Completion: October 27, 2017
• Last Updated: November 23, 2022

Record last verified: 2022-11

Locations

CZ (1)