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

Healthy Subjects Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02770222
• Other study ID #: AC-065-113
• Secondary ID: 2016-000811-34
• Status: Completed
• Phase: Phase 1
• First received: May 11, 2016
• Last updated: July 20, 2016
• Start date: June 2016
• Est. completion date: July 2016

Study information

• Verified date: July 2016
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Selexipag
Two selexipag film-coated tablets of 200 µg as single oral dose (total dose = 400 µg)
• Gemfibrozil
Gemfibrozil film-coated tablet of 600 mg administered orally b.i.d. from Day 1 to Day 9
• Rifampicin
Rifampicin film-coated tablet of 600 mg administered orally o.d.from Day 1 to Day 9

Locations

Country	Name	City	State
Germany	Investigator Site	Kiel

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of treatment-emergent adverse events and serious adverse events	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)	Yes
Other	Incidence of safety events of interest	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)	Yes
Primary	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)	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)	No
Primary	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)	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)	No
Secondary	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)	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)	No
Secondary	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)	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)	No
Secondary	Terminal elimination half-life (t1/2) of selexipag and ACT-333679	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)	No