Potential Pharmacokinetic Interaction Between Selexipag and Midazolam in Healthy Male Subjects

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02791815
• Other study ID #: AC-065-114
• Secondary ID: 2016-000856-83
• Status: Completed
• Phase: Phase 1
• First received: June 2, 2016
• Last updated: October 12, 2016
• Start date: July 2016
• Est. completion date: September 2016

Study information

• Verified date: October 2016
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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)

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Midazolam
Single oral dose of 7.5 mg midazolam (tablet)
• Selexipag
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. )

Locations

Country	Name	City	State
France	Investigator Site	Gieres

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

France, 

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 39 days (from Day 1 of Period 1 to end of study of Period 2)	Yes
Primary	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	From pre-dose up to 24 hours after midazolam admisnitration for each treatment period	No
Primary	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	From pre-dose up to 24 hours after midazolam admisnitration for each treatment period	No
Secondary	Cmax of 1-hydroxymidazolam following administration of midazolam alone and in combination with selexipag		From pre-dose up to 24 hours after midazolam admisnitration	No
Secondary	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	No
Secondary	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	From pre-dose up to 24 hours after midazolam admisnitration	No
Secondary	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	From pre-dose up to 24 hours after midazolam admisnitration	No
Secondary	Trough concentration of selexipag and its metabolite ACT-333679 at steady-state	Trough concentrations are measured before morning administration of selexipag	Days 1, 4, 7, 10,12 and 13	No