Clinical trial NCT02770222: A Clinical Study to Investigate the Effect of Gemfibrozil or Rifampicin on Blood Concentrations of Selexipag in Healthy Subjects
Official title: A Single-center, Open-label, Randomized, Two-part, Two-treatment, Two-period Crossover Study to Investigate the Effect of Gemfibrozil or Rifampicin on the Pharmacokinetics of Selexipag and Its Metabolite ACT-333679 in Healthy Male Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Pharmacokinetics
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2016-05-12
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The primary objectives of this 2-part drug interaction study are as follows:

* To evaluate the effect of gemfibrozil on the pharmacokinetics (i.e., amount in the blood) of selexipag and its metabolite ACT-333679 (Part I).
* To evaluate the effect of rifampicin on the pharmacokinetics of selexipag and its metabolite ACT-333679 (Part II).

Detailed description: Because non-clinical studies have shown that selexipag and its active metabolite, ACT-333679, are substrates for cytochrome P450 2C8 (CYP2C8), the present clinical study aims at investigating the effect of a strong inhibitor (gemfibrozil) and a moderate inducer (rifampicin) of CYP2C8 on the pharmacokinetic of selexipag and ACT-333679 as recommended by the FDA's Guidance for Industry Drug Interaction Studies (FDA, 2012).

Eligibility criteria: Inclusion Criteria:

* Signed informed consent form.
* Male subjects aged between 18 and 55 years (inclusive) at screening.
* Body mass index of 18.0 to 28.0 kg/m2 (inclusive) at screening.
* Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests at screening.

Exclusion Criteria:

* Any contraindication to gemfibrozil or rifampicin treatment.
* History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might put the subject at risk of participation in the study or interfere with the absorption, distribution, metabolism or excretion of the study treatments.
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Primary outcomes:
measure: Area under the plasma concentration-time curve from zero to infinity [AUC(0-inf)] of selexipag and ACT-333679
timeFrame: Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours)
measure: Maximum plasma concentration (Cmax) of selexipag and ACT-333679
timeFrame: Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours)
Secondary outcomes:
measure: Area under the plasma concentration-time curve from zero to time t of the last measured concentration above the limit of quantification [(AUC(0-t)] of selexipag and ACT-333679
timeFrame: Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours)
measure: Time to reach maximum plasma concentration (tmax) of selexipag and ACT-333679
timeFrame: Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours)
measure: Terminal elimination half-life (t1/2) of selexipag and ACT-333679
timeFrame: Blood samples at different time points from pre-dose up to 72 hours after selexipag administration in each study period (except for the period with co-administration of gemfibrozil: up to 144 hours)
Other outcomes:
measure: Incidence of treatment-emergent adverse events and serious adverse events
timeFrame: Up to 35 days (from first study drug administration to end of study visit)
measure: Incidence of safety events of interest
timeFrame: Up to 35 days (from first study drug administration to end of study visit)
Locations:
Study officials:
affiliation: Actelion
name: Shirin Bruderer, PhD
role: STUDY_DIRECTOR
References:
citation: Bruderer S, Petersen-Sylla M, Boehler M, Remenova T, Halabi A, Dingemanse J. Effect of gemfibrozil and rifampicin on the pharmacokinetics of selexipag and its active metabolite in healthy subjects. Br J Clin Pharmacol. 2017 Dec;83(12):2778-2788. doi: 10.1111/bcp.13379. Epub 2017 Aug 16.