Healthy Subjects
Conditions
Keywords
Pharmacokinetics
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).
Interventions
DRUGSelexipag
Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg)
DRUGGemfibrozil
Gemfibrozil film-coated tablet of 600 mg administered orally b.i.d. from Day 1 to Day 9
DRUGRifampicin
Rifampicin film-coated tablet of 600 mg administered orally o.d.from Day 1 to Day 9
Sponsors
Actelion
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve from zero to infinity [AUC(0-inf)] of selexipag and ACT-333679 | 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) | AUC(0-inf) is calculated for selexipag and its metabolite, ACT-333679, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) |
| Maximum plasma concentration (Cmax) of selexipag and ACT-333679 | 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) | Cmax is directly derived from the individual plasma concentration-time curves for selexipag and its metabolite, ACT-333679, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal elimination half-life (t1/2) of selexipag and ACT-333679 | 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) | t1/2 is the period of time required for the concentration levels of selexipag or ACT-333679 to be reduced by one-half, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) |
| Time to reach maximum plasma concentration (tmax) of selexipag and ACT-333679 | 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) | tmax is directly derived from the individual plasma concentration-time curves for selexipag and its metabolite, ACT-333679, following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) |
| 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 | 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) | AUC(0-t) is calculated for selexipag and ACT-333679,following administration of selexipag alone or concomitantly with gemfibrozil (Part I) or rifampicin (Part II) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events and serious adverse events | Up to 35 days (from first study drug administration to end of study visit) | A treatment-emergent AE is any AE temporally associated with the use of a study treatment, whether or not considered related to the study treatment |
| Incidence of safety events of interest | Up to 35 days (from first study drug administration to end of study visit) | Include any abnormalities in ECG, vital signs or laboratory test results |
Outcome results
None listed