A Clinical Study to Assess the Effect of Clopidogrel on the Pharmacokinetics of Selexipag and Its Active Metabolite in Healthy Male Subjects

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03496506
• Other study ID #: AC-065-117
• Status: Completed
• Phase: Phase 1
• Start date: March 5, 2018
• Est. completion date: May 18, 2018

Study information

• Verified date: May 2018
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: May 18, 2018
• Est. primary completion date: May 10, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Selexipag
Each film-coated tablet contains 200 microgram (mcg) of selexipag (oral use)
• Clopidogrel
Each film-coated tablet containing 75 mg of clopidogrel (oral use)

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit (CPU)	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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)