A Clinical Study to Investigate the Effect of Gemfibrozil or Rifampicin on Blood Concentrations of Selexipag in Healthy Subjects

Actelion40 enrolled

Overview

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).

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy Subjects

Interventions

SelexipagDRUG

Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg)

GemfibrozilDRUG

Gemfibrozil film-coated tablet of 600 mg administered orally b.i.d. from Day 1 to Day 9

RifampicinDRUG

Rifampicin film-coated tablet of 600 mg administered orally o.d.from Day 1 to Day 9

Eligibility

Sex: MALEMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Area under the plasma concentration-time curve from zero to infinity [AUC(0-inf)] of selexipag and ACT-333679

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)

Time frame: 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)

Maximum plasma concentration (Cmax) of selexipag and ACT-333679

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 Outcomes

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

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)

Time to reach maximum plasma concentration (tmax) of selexipag and ACT-333679

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)

Data from ClinicalTrials.gov

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