Clinical trial NCT03496506: A Clinical Study to Assess the Effect of Clopidogrel on the Pharmacokinetics of Selexipag and Its Active Metabolite in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: selexipag
clopidogrel
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2018-04-12
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, two-treatment, one-sequence, cross-over study
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the plasma concentration-time profile of selexipag and ACT-333679 during a dose interval (AUC-tau)
timeFrame: 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
measure: Maximal plasma concentration of selexipag and ACT-333679 (Cmax)
timeFrame: 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 outcomes:
measure: Trough plasma concentration of selexipag and ACT-333679 (Ctrough)
timeFrame: 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
measure: Time to reach Cmax (tmax)
timeFrame: 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
measure: Number of participants with any treatment-emergent adverse events (TEAEs) including serious adverse events
timeFrame: From the first selexipag administration on Day 1 up to Day 18 (about 1 week after the last administration of selexipag)
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit (CPU)
Study officials:
affiliation: Actelion
name: Shirin Bruderer
role: STUDY_DIRECTOR
References:
citation: Axelsen LN, Poggesi I, Rasschaert F, Perez Ruixo JJ, Bruderer S. Clopidogrel, a CYP2C8 inhibitor, causes a clinically relevant increase in the systemic exposure to the active metabolite of selexipag in healthy subjects. Br J Clin Pharmacol. 2021 Jan;87(1):119-128. doi: 10.1111/bcp.14365. Epub 2020 Jun 5.