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)

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Aprocitentan
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>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<br>* Tablet for oral administration<br>|
| Experimental: Treatment B1<br>25 mg ACT-132577 will be administered o.d. from Day 5 to Day 12 | Drug: Aprocitentan<br>* Capsule for oral administration<br>* Other names: ACT-132577;|
| Experimental: Treatment B2<br>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: Aprocitentan<br>* Capsule for oral administration<br>* Other names: ACT-132577;Drug: Rosuvastatin<br>* Tablet for oral administration<br>|

What is the study measuring?
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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 |