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

July 20, 2016 updated by: Actelion

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.

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Kiel, Germany, 24105
        • Investigator site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1, sequence AB
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.
Drug: Selexipag
Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg)
Other Names:
  • ACT-293987
Drug: Gemfibrozil
Gemfibrozil film-coated tablet of 600 mg administered orally b.i.d. from Day 1 to Day 9
Experimental: Part 1, sequence BA
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.
Drug: Selexipag
Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg)
Other Names:
  • ACT-293987
Drug: Gemfibrozil
Gemfibrozil film-coated tablet of 600 mg administered orally b.i.d. from Day 1 to Day 9
Experimental: Part 2, sequence AB
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.
Drug: Selexipag
Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg)
Other Names:
  • ACT-293987
Drug: Rifampicin
Rifampicin film-coated tablet of 600 mg administered orally o.d.from Day 1 to Day 9
Experimental: Part 2, sequence BA
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.
Drug: Selexipag
Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg)
Other Names:
  • ACT-293987
Drug: Rifampicin
Rifampicin film-coated tablet of 600 mg administered orally o.d.from Day 1 to Day 9

What is the study measuring?

Primary Outcome Measures

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

Outcome Measure
Measure Description
Time Frame
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
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)
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)
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)
Time to reach maximum plasma concentration (tmax) of selexipag and ACT-333679
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)
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)
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)
Terminal elimination half-life (t1/2) of selexipag and ACT-333679
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)
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)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-emergent adverse events and serious adverse events
Time Frame: 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
Up to 35 days (from first study drug administration to end of study visit)
Incidence of safety events of interest
Time Frame: 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
Up to 35 days (from first study drug administration to end of study visit)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Actelion

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2016

Primary Completion (Actual)

July 1, 2016

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

May 11, 2016

First Submitted That Met QC Criteria

May 11, 2016

First Posted (Estimate)

May 12, 2016

Study Record Updates

Last Update Posted (Estimate)

July 21, 2016

Last Update Submitted That Met QC Criteria

July 20, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-065-113
  • 2016-000811-34 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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