Clinical trial NCT02791815: Potential Pharmacokinetic Interaction Between Selexipag and Midazolam in Healthy Male Subjects
Official title: A Single-center, Open-label, Randomized, Two-treatment Crossover Study to Investigate the Effect of Selexipag on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: selexipag
pharmacokinetics
midazolam
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2016-06-07
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The primary purpose of this study is to evaluate the effect of repeated doses of selexipag on the pharmacokinetics of a single oral dose of midazolam (i.e., how long and how much midazolam is present in the blood)

Detailed description: In order to exclude an inductive effect of selexipag in the gastrointestinal tract, this study aims at investigating the effect of selexipag on the PK of midazolam, a sensitive substrate of both hepatic and intestinal cytochrome P450 3A4 (CYP3A4).

Eligibility criteria: Key Inclusion Criteria:

* Signed informed consent form
* Age from 18 to 45 years (inclusive) at screening
* Body mass index (BMI) from 18.0 to 28.0 kg/m2 (inclusive) at screening
* Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests

Key Exclusion Criteria:

* Any contraindication to the study treatments
* History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may 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 the subject's full participation in the study or compliance with the protocol

Primary outcomes:
measure: Cmax of midazolam following administration of midazolam alone and in combination with selexipag
timeFrame: From pre-dose up to 24 hours after midazolam admisnitration for each treatment period
measure: AUC(0-inf) of midazolam following administration of midazolam alone and in combination with selexipag
timeFrame: From pre-dose up to 24 hours after midazolam admisnitration for each treatment period
Secondary outcomes:
measure: Cmax of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag
timeFrame: From pre-dose up to 24 hours after midazolam admisnitration
measure: AUC(0-inf) of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag
timeFrame: From pre-dose up to 24 hours after midazolam admisnitration
measure: tmax of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag
timeFrame: From pre-dose up to 24 hours after midazolam admisnitration
measure: t½ of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag.
timeFrame: From pre-dose up to 24 hours after midazolam admisnitration
measure: Trough concentration of selexipag and its metabolite ACT-333679 at steady-state
timeFrame: Days 1, 4, 7, 10,12 and 13
Other outcomes:
measure: Incidence of treatment-emergent adverse events and serious adverse events
timeFrame: Up to 39 days (from Day 1 of Period 1 to end of study of Period 2)
Locations:
city: Gieres
country: France
facility: Investigator Site
Study officials:
affiliation: Actelion
name: Pierre-Eric Juif, PhD
role: STUDY_DIRECTOR
References: