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

NCT02770222 | Completed Phase 1

• 2 other identifiers: AC-065-1132016-000811-34
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Healthy Subjects

Keywords

Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• 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)

• 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)

Secondary Outcomes (3)

• 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)

• 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)

• 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)

Other Outcomes (2)

• Incidence of treatment-emergent adverse events and serious adverse events

  Up to 35 days (from first study drug administration to end of study visit)

• Incidence of safety events of interest

  Up to 35 days (from first study drug administration to end of study visit)

Study Arms (4)

Part 1, sequence AB

EXPERIMENTAL

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; Drug: Gemfibrozil

Part 1, sequence BA

EXPERIMENTAL

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; Drug: Gemfibrozil

Part 2, sequence AB

EXPERIMENTAL

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; Drug: Rifampicin

Part 2, sequence BA

EXPERIMENTAL

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; Drug: Rifampicin

Interventions

Selexipag DRUG

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

Also known as: ACT-293987

Part 1, sequence AB; Part 1, sequence BA; Part 2, sequence AB; Part 2, sequence BA

Gemfibrozil DRUG

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

Part 1, sequence AB; Part 1, sequence BA

Rifampicin DRUG

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

Part 2, sequence AB; Part 2, sequence BA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• Bruderer S, Petersen-Sylla M, Boehler M, Remenova T, Halabi A, Dingemanse J. Effect of gemfibrozil and rifampicin on the pharmacokinetics of selexipag and its active metabolite in healthy subjects. Br J Clin Pharmacol. 2017 Dec;83(12):2778-2788. doi: 10.1111/bcp.13379. Epub 2017 Aug 16.

  PMID: 28715853 DERIVED

MeSH Terms

Interventions

selexipag; Gemfibrozil; Rifampin

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Volatile; Fatty Acids; Lipids; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Shirin Bruderer, PhD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: May 12, 2016
• Study Start: June 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: February 3, 2025

Record last verified: 2025-01