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

Actelion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Selexipag; Drug: Rifampicin; Drug: Gemfibrozil

Study type: Interventional

Funder types: Industry

Identifiers

NCT02770222

2016-000811-34 (EudraCT Number)

AC-065-113

Details and patient eligibility

About

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).

Full 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).

Enrollment: 40 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

Part 1, sequence AB

Experimental group

Description:

Subjects participate in two study periods: During the first period (Treatment A), they receive oral selexipag on Day 1. During the second period (Treatment B), they receive multiple oral dose of gemfibrozil from Day 1 to Day 9. Subjects also receive a single oral dose of selexipag on Day 4 concomitantly with gemfibrozil. There is a washout period of 14 to 21 days between the two periods.

Treatment:

Drug: Gemfibrozil

Drug: Selexipag

Part 1, sequence BA

Experimental group

Description:

Subjects participate in two study periods: During the first period (Treatment B), they receive multiple oral dose of gemfibrozil from Day 1 to Day 9. They also receive a single oral dose of selexipag on Day 4 concomitantly with gemfibrozil. During the second period (Treatment A) they receive oral selexipag on Day 1. There is a washout period of 14 to 21 days between the two periods.

Treatment:

Drug: Gemfibrozil

Drug: Selexipag

Part 2, sequence AB

Experimental group

Description:

Subjects participate in two study periods: During the first period (Treatment A), they receive oral selexipag on Day 1. During the second period (Treatment B), they receive rifampicin once daily from Day 1 to Day 9. Subjects also receive a single oral dose of selexipag on Day 7 together with the dose of rifampicin.There is a washout period of 14 to 21 days between the two periods.

Treatment:

Drug: Rifampicin

Drug: Selexipag

Part 2, sequence BA

Experimental group

Description:

Subjects participate in two study periods: During the first period (Treatment B), they receive rifampicin once daily from Day 1 to Day 9. Subjects also receive a single oral dose of selexipag on Day 7 together with the dose of rifampicin. During the second period (Treatment A), they receive oral selexipag on Day 1. There is a washout period of 14 to 21 days between the two periods.

Treatment:

Drug: Rifampicin

Drug: Selexipag