Potential Pharmacokinetic Interaction Between Selexipag and Midazolam in Healthy Male Subjects

Phase 1

Completed

• Conditions: Healthy Subjects
• Interventions: Drug: Midazolam; Drug: Selexipag

• Registration Number: NCT02791815
• Lead Sponsor: Actelion

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).

Study Timeline

• Study First Submitted: 2016-06-02
• Study First Submitted QC: 2016-06-02
• Study First Posted: 2016-06-07
• Study Start: 2016-07
• Primary Completion: 2016-09
• Study Completion: 2016-09
• Status Verified: 2016-10
• Last Update Submitted: 2016-10-12
• Last Update Posted: 2016-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence AB	Midazolam	Subjects participate in two study periods: During the first period, they receive a single oral dose of midazolam on Day 1. During the second period, they receive oral selexipag alone from Day 1 to Day 11 and selexipag + midazolam on Day 12. There is a washout period of 14 to 21 days between the two periods.
Sequence BA	Midazolam	Subjects participate in two study periods: During the first period, they receive oral selexipag alone from Day 1 to Day 11 and selexipag + midazolam on Day 12. During the second period, they receive a single oral dose of midazolam on Day 1. There is a washout period of 14 to 21 days between the two periods.
Sequence AB	Selexipag	Subjects participate in two study periods: During the first period, they receive a single oral dose of midazolam on Day 1. During the second period, they receive oral selexipag alone from Day 1 to Day 11 and selexipag + midazolam on Day 12. There is a washout period of 14 to 21 days between the two periods.
Sequence BA	Selexipag	Subjects participate in two study periods: During the first period, they receive oral selexipag alone from Day 1 to Day 11 and selexipag + midazolam on Day 12. During the second period, they receive a single oral dose of midazolam on Day 1. There is a washout period of 14 to 21 days between the two periods.

Primary Outcome Measures

Name	Time	Method
Cmax of midazolam following administration of midazolam alone and in combination with selexipag	From pre-dose up to 24 hours after midazolam admisnitration for each treatment period	Cmax is the maximum observed plasma concentration and is directly derived from the individual plasma concentration time curves of midazolam
AUC(0-inf) of midazolam following administration of midazolam alone and in combination with selexipag	From pre-dose up to 24 hours after midazolam admisnitration for each treatment period	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

Secondary Outcome Measures

Name	Time	Method
Cmax of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag	From pre-dose up to 24 hours after midazolam admisnitration
Trough concentration of selexipag and its metabolite ACT-333679 at steady-state	Days 1, 4, 7, 10,12 and 13	Trough concentrations are measured before morning administration of selexipag
tmax of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag	From pre-dose up to 24 hours after midazolam admisnitration	tmax is the time to reach Cmax of midazolam and its metabolite (1-hydroxymidazolam), respectively
t½ of midazolam and 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag.	From pre-dose up to 24 hours after midazolam admisnitration	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
AUC(0-inf) of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag	From pre-dose up to 24 hours after midazolam admisnitration

Trial Locations

Locations (1)

Investigator Site; 🇫🇷 Gieres, France