A Clinical Study to Assess the Effect of Clopidogrel on the Pharmacokinetics of Selexipag and Its Active Metabolite 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 clopidogrel on the pharmacokinetics of selexipag and its active metabolite (ACT-333679) in healthy male adults (by determining the blood concentrations of selexipag and its metabolite). Also, the safety of selexipag when administered alone or with clopidogrel will be assessed.

Official Title
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A Single-center, Open-label, Two-treatment, One-sequence, Cross-over Study to Investigate the Effect of Clopidogrel on the Pharmacokinetics of Selexipag and Its Active Metabolite, ACT-333679, in Healthy Male Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Selexipag
* Drug: Clopidogrel


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. Healty male subjects aged between 18 and 45 years (inclusive) at screening. Body mass index from 18.0 to 28.0 kg/m2 (inclusive) at screening. Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 45-90 bpm (inclusive). Exclusion Criteria: Any contraindication included in the SmPC of selexipag or clopidogrel treatment. History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study treatments. History or clinical evidence of any disorder of hemostasis, hemorrhagic diathesis, nose or gingival bleeding, hemophilia, thrombotic thrombocytopenic purpura, presence of any lesions with a propensity to bleed (particularly gastrointestinal and intraocular), history of bleeding complications after surgical procedures such as tooth extraction Previous history of stroke, fainting, collapse, syncope, orthostatic hypotension,vasovagal reactions, head injury. Excessive caffeine consumption Nicotine consumption within 3 months prior to screening, and inability to refrain from nicotine consumption during the course of the study Previous treatment with any prescribed medications (including vaccines) or over the counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 2 weeks prior to first selexipag administration. Subjects with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's 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
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, two-treatment, one-sequence, cross-over study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequential treatment arm<br>Subjects receive 1 tablet of selexipag twice daily from Day 1 to Day 9 and 1 tablet in the morning of Day 10. In the morning of Day 4 and 1 hour before the administration of selexipag, they receive 4 tablets of clopidogrel. Then from Day 5 to Day 10, 1 hour before the morning administration of selexipag, they receive 1 tablet of clopidogrel . | Drug: Selexipag<br>* Each film-coated tablet contains 200 microgram (mcg) of selexipag (oral use)<br>* Other names: ACT-293987;Drug: Clopidogrel<br>* Each film-coated tablet containing 75 mg of clopidogrel (oral use)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time profile of selexipag and ACT-333679 during a dose interval (AUC-tau) | AUC-tau for selexipag and ACT-333679 is calculated on the basis of the actual blood sampling time points drawn during the 12-hour interval after the morning administration of selexipag administered either alone (Day 3) or concomitantly with clopidogrel (Day 4 and Day 10) | Blood samples at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post-dose on Day 3, Day 4 and Day 10 | 
| Maximal plasma concentration of selexipag and ACT-333679 (Cmax) | Cmax is directly derived from the individual plasma concentration-time curves for selexipag and ACT-333679, following administration of selexipag alone (Day 3) or concomitantly with clopidogrel (Day 4 and Day 10) | Blood samples at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post-dose on Day 3, Day 4 and Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough plasma concentration of selexipag and ACT-333679 (Ctrough) | Ctrough is the concentration of selexipag and ACT-333679 directly measured in the blood samples collected prior to the morning and evening administrations of selexipag | Blood samples from Day 1 to Day 9 before the morning and evening administrations of selexipag and on Day 10 before the morning administration of selexipag | 
| Time to reach Cmax (tmax) | tmax is the time to reach the maximal plasma concentration of selexipag and ACT-333679 and it is directly derived from the individual plasma concentration-time curves for selexipag and ACT-333679, following administration of selexipag alone (Day 3) or concomitantly with clopidogrel (Day 4 and Day 10) | Blood samples at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post-dose on Day 3, Day 4 and Day 10 | 
| Number of participants with any treatment-emergent adverse events (TEAEs) including serious adverse events | A treatment-emergent adverse event is any adverse event temporally associated with the use of a study treatment, whether or not considered related to the study treatment | From the first selexipag administration on Day 1 up to Day 18 (about 1 week after the last administration of selexipag) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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selexipag, clopidogrel