Potential Pharmacokinetic Interaction Between Selexipag and Midazolam in Healthy Male Subjects

NCT02791815 | Completed Phase 1

• 2 other identifiers: AC-065-1142016-000856-83
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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)

Conditions

Healthy Subjects

Keywords

selexipag; pharmacokinetics; midazolam

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (5)

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

  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

  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

  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.

  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

Other Outcomes (1)

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

  Up to 39 days (from Day 1 of Period 1 to end of study of Period 2)

Study Arms (2)

Sequence AB

EXPERIMENTAL

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.

Drug: Midazolam; Drug: Selexipag

Sequence BA

EXPERIMENTAL

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.

Drug: Midazolam; Drug: Selexipag

Interventions

Midazolam DRUG

Single oral dose of 7.5 mg midazolam (tablet)

Sequence AB; Sequence BA

Selexipag DRUG

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. )

Also known as: ACT-293987

Sequence AB; Sequence BA

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Investigator Site

Gières, 38610, France

Location

MeSH Terms

Interventions

Midazolam; selexipag

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pierre-Eric Juif, PhD

  Actelion

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 7, 2016
• Study Start: July 1, 2016
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: October 13, 2016

Record last verified: 2016-10

Locations

FR (1)