A Clinical Study to Assess the Effect of Clopidogrel on the Pharmacokinetics of Selexipag and Its Active Metabolite in Healthy Male Subjects
- Registration Number
- NCT03496506
- Lead Sponsor
- Actelion
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 22
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sequential treatment arm Selexipag 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 . Sequential treatment arm Clopidogrel 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 .
- Primary Outcome Measures
Name Time Method Area under the plasma concentration-time profile of selexipag and ACT-333679 during a dose interval (AUC-tau) 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 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)
Maximal plasma concentration of selexipag and ACT-333679 (Cmax) 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 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)
- Secondary Outcome Measures
Name Time Method Trough plasma concentration of selexipag and ACT-333679 (Ctrough) 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 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
Number of participants with any treatment-emergent adverse events (TEAEs) including serious adverse events From the first selexipag administration on Day 1 up to Day 18 (about 1 week after the last administration of selexipag) 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
Time to reach Cmax (tmax) 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 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)
Trial Locations
- Locations (1)
Clinical Pharmacology Unit (CPU)
🇧🇪Merksem, Belgium