A Study to Investigate the Effect of ACT-132577 on the Pharmacokinetics of Midazolam and 1-hydroxy Midazolam in Healthy Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of ACT-132577 on the pharmacokinetics of midazolam and 1-hydroxy midazolam and to evaluate the safety and tolerability of ACT-132577 when administered alone and in combination with midazolam.

Official Title
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A Single-center, Open-label, Two-treatment Study to Investigate the Effect of ACT-132577 at Steady State on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxy Midazolam in Healthy Male Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Midalozam
* Drug: Aprocitentan


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 Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at screening Healthy on the basis of medical history, physical examination, cardiovascular assessments and serology and laboratory tests Exclusion Criteria: 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A (Midazolam)<br>Single dose of Midazolam 8 mg on Day 1 | Drug: Midalozam<br>* Syrup for oral use<br>|
| Experimental: Treatment B1 (ACT-132577)<br>Single dose of ACT-132577 150 mg on Day 2; single dose of ACT-132577 50 mg on Day 3, Day 4, and Day 5. | Drug: Aprocitentan<br>* Capsules for oral use<br>* Other names: ACT-132577;|
| Experimental: Treatment B2 (Midazolam + ACT-132577)<br>Single dose of Midazolam 8 mg and single dose of ACT-132577 50 mg on Day 6 | Drug: Midalozam<br>* Syrup for oral use<br>Drug: Aprocitentan<br>* Capsules for oral use<br>* Other names: ACT-132577;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plama concentration (Cmax) | Cmax of midazolam and 1-hydroxy midazolam following administration of midazolam alone and in combination with ACT-132577 | Midazolam PK sampling on Days 1, 2, 6 and 7 | 
| Area under the plasma concentration-time curve from zero to infinity (AUC0-∞) | AUC0-∞ of midazolam and 1-hydroxy midazolam following administration of midazolam alone and in combination with ACT-132577 | Midazolam PK sampling on Days 1, 2, 6 and 7 | 
| Time to reach Cmax (tmax) | Tmax of midazolam and 1-hydroxy midazolam following administration of midazolam alone and in combination with ACT-132577 | Midazolam PK sampling on Days 1, 2, 6 and 7 | 
| Terminal half-life (t1/2) | T1/2 of midazolam and 1-hydroxy midazolam following administration of midazolam alone and in combination with ACT-132577 | Midazolam PK sampling on Days 1, 2, 6 and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events |  | From Day 1 to Follow-up (for up to 38 days) | 
| Number of subjects with serious adverse events |  | From Screening to Follow-up (for up to 59 days) |