Potential Pharmacokinetic Interaction Between Selexipag and Midazolam in Healthy Male Subjects

Actelion20 enrolled

Overview

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)

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Masking

NONE

Enrollment

Conditions

Healthy Subjects

Interventions

MidazolamDRUG

Single oral dose of 7.5 mg midazolam (tablet)

SelexipagDRUG

Oral administration of selexipag (200 µg film-coated tablet) for 12 consecutive days (with a titration scheme from 400 to 1600 μg b.i.d. )

Eligibility

Sex: MALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Investigator Site

Gières, France

Outcomes

Primary Outcomes

Cmax of midazolam following administration of midazolam alone and in combination with selexipag

Cmax is the maximum observed plasma concentration and is directly derived from the individual plasma concentration time curves of midazolam

Time frame: From pre-dose up to 24 hours after midazolam admisnitration for each treatment period

AUC(0-inf) of midazolam following administration of midazolam alone and in combination with selexipag

AUC(0-inf) is the area under the plasma concentration-time curves of midazolam, calculated from time 0 (pre-dose) to the extrapolated infinite time

Time frame: From pre-dose up to 24 hours after midazolam admisnitration for each treatment period

Secondary Outcomes

Cmax of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag

Time frame: From pre-dose up to 24 hours after midazolam admisnitration

AUC(0-inf) of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag

Time frame: From pre-dose up to 24 hours after midazolam admisnitration

tmax of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag

tmax is the time to reach Cmax of midazolam and its metabolite (1-hydroxymidazolam), respectively

Time frame: From pre-dose up to 24 hours after midazolam admisnitration

t½ of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag.

t½ is the terminla half-life of midazolam and its metabolite (1-hydroxymidazolam), and corresponds to the period of time required for the concentration levels of midazolam and its metabolite to be reduced by one-half, respectively

Data from ClinicalTrials.gov

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