A Clinical Study to Investigate the Potential Interactions Between Food and ACT-541468 and Between ACT-541468 and Midazolam

NCT03017495 | Completed Phase 1

• 2 other identifiers: AC-078-1042016-003490-18
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The main objectives of this phase 1 trial are to evaluate the effect of food on the pharmacokinetics (i.e. how long and how much a compound is present in the blood) of ACT-541468 and to evaluate whether ACT-541468 can affect the pharmacokinetics of midazolam, a CYP3A4 substrate.

Conditions

Healthy Subjects

Keywords

food-drug interaction; drug-drug interaction; pharmacokinetics

Outcome Measures

Primary Outcomes (12)

• Maximum plasma concentration (Cmax) of ACT-541468

  Cmax is directly determined from the plasma concentrations-time curves of ACT-541468

  PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only

• Time to reach Cmax (tmax) of ACT-541468

  Tmax is directly determined from the plasma concentrations-time curves of ACT-541468

  PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only

• Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468

  AUC is calculated from time zero to 24 hours post dose

  PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only

• Terminal half-life (t1/2) of ACT-541468

  t1/2 is calculated from the plasma concentrations-time curves of ACT-541468

  PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only

• Maximum plasma concentration (Cmax) of midazolam

  Cmax is directly obtained from the plasma concentrations-time curves of midazolam

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

• Time to reach Cmax (tmax) of midazolam

  Tmax is directly obtained from the plasma concentrations-time curves of midazolam

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

• Area under the plasma concentration-time curve [AUC(0-24)] of midazolam

  AUC is calculated from time zero to 24 hours post dose

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

• Terminal half-life (t1/2) of midazolam

  t1/2 is calculated from the plasma concentrations-time curves of midazolam

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

• Maximum plasma concentration (Cmax) of 1-hydroxymidazolam

  Cmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

• Time to reach Cmax (tmax) of 1-hydroxymidazolam

  Tmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

• Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam

  AUC is calculated from time zero to 24 hours post dose

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

• Terminal half-life (t1/2) of 1-hydroxymidazolam

  t1/2 is calculated from the plasma concentrations-time curves of 1-hydroxymidazolam

  PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose

Secondary Outcomes (5)

• Number of subjects with treatment-emergent adverse events and serious adverse events

  From baseline to end-of-study, i.e.,maximum 5 days after Day 8

• Maximum plasma concentration (Cmax) of ACT-541468 metabolites

  PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose

• Time to reach Cmax (tmax) of ACT-541468 metabolites

  PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose

• Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 metabolites

  PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose

• Terminal half-life (t1/2) of ACT-541468 metabolites

  PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose

Study Arms (1)

Food effect and Drug-Drug interaction

EXPERIMENTAL

Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted).

Drug: Midazolam; Drug: ACT-541468

Interventions

Midazolam DRUG

2 mg/mL oral solution

Food effect and Drug-Drug interaction

ACT-541468 DRUG

Hard gelatin capsules for oral use at a strength of 25 mg

Food effect and Drug-Drug interaction

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
• Male subjects aged from 18 to 45 years (inclusive) at screening
• Body mass index (BMI) from 18.0 to 30.0 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
• History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score \< 0
• 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

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

Investigator Site

Kiel, 24105, Germany

Location

MeSH Terms

Interventions

Midazolam; daridorexant

Intervention Hierarchy (Ancestors)

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

Study Officials

• Marie-Laure Boof, PhD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2017
• First Posted: January 11, 2017
• Study Start: January 1, 2017
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

DE (1)