A Study in Healthy Male Subjects to Investigate Whether Administration of ACT-132577 Can Affect Rosuvastatin's Fate in the Body (Amount and Time of Presence in the Blood)

A Single-center, Open-label, One-sequence, Two-treatment Study to Investigate the Effect of ACT-132577 at Steady State on the Pharmacokinetics of Rosuvastatin in Healthy Male Subjects

The primary purpose of this study is to investigate the effect of Aprocitentan (ACT-132577) at steady state on the pharmacokinetics of single-dose rosuvastatin in healthy male subjects

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Aprocitentan

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Plzen, Czechia, 32300
    • Cepha s.r.o

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed informed consent in the local language prior to any study mandated procedure;
• Healthy male subjects aged 18 to 45 years (inclusive) at screening;
• Body mass index of 18.0 to 28.0 kg/m2 (inclusive) at screening;
• Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests;
• Hemoglobin ≥ 135 g/L at screening.

Exclusion Criteria:

• Known allergic reactions or hypersensitivity to ACT-132577, rosuvastatin, any drug of the same classes, or any of their excipients;
• Any contraindication for rosuvastatin treatment;
• History or clinical evidence of myopathy;
• Asian or Indian-Asian ethnicity;
• Known hypersensitivity or allergy to natural rubber latex;
• Previous exposure to ACT-132577;
• Treatment with rosuvastatin within 3 months prior to screening;
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A; In the morning of Day 1, a single dose of 10 mg rosuvastatin will be administered in the fasted state followed by an observation period of 96 h	Drug: Rosuvastatin; Tablet for oral administration
EXPERIMENTAL: Treatment B1; 25 mg ACT-132577 will be administered o.d. from Day 5 to Day 12	Drug: Aprocitentan; Capsule for oral administration; Other Names: ACT-132577
EXPERIMENTAL: Treatment B2; In the morning of Day 13, a single dose of 10 mg rosuvastatin will be administered in the fasted state, concomitantly with 25 mg ACT-132577, followed by an observation period of 120 h. Doses of 25 mg ACT-132577 will be administered o.d. from Day 14 to Day 17.	Drug: Rosuvastatin; Tablet for oral administration; Drug: Aprocitentan; Capsule for oral administration; Other Names: ACT-132577

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) of rosuvastatin	Cmax of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to Day 29
Time to reach Cmax (tmax) of rosuvastatin	tmax of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to Day 29
Terminal half-life (t1/2) of rosuvastatin	t1/2 of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to Day 29
Area under the plasma concentration-time curves during a dosing interval [AUC(0-t)] of rosuvastatin	AUC(0-t) of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profiles	Up to Day 29
Area under the plasma concentration-time curves from time 0 to inf [AUC(0-inf)] of rosuvastatin	AUC(0-inf) of rosuvastatin will be derived by non-compartmental analysis of the plasma concentration-time profile	Up to Day 29
Trough (pre-dose) plasma concentrations (Ctrough) of ACT-132577	Ctrough of ACT-132577 will be derived by non-compartmental analysis of the plasma concentration-time profile	Up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	Treatment emergent adverse events and treatment emergent serious adverse events will be evaluated throughout the study	Up to Day 29
Changes from baseline in electrocardiogram (ECG) variables	ECG variables are to be recorded at rest using a standard 12-lead ECG	Up to Day 29
Changes from baseline in blood pressure	Blood pressure (mmHg) measured using an automatic oscillometric device	Up to Day 29
Changes from baseline in pulse rate	Pulse rate (bpm) measured using an automatic oscillometric device	Up to Day 29

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 10, 2017
• Primary Completion (ACTUAL): September 18, 2017
• Study Completion (ACTUAL): September 18, 2017

Study Registration Dates

• First Submitted: August 8, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (ACTUAL): August 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 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: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: AC-080-106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No