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Completed

NCT Number: NCT03017495

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

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.

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Key information

Conditions

Healthy Subjects

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Investigator Site

Kiel, 24105, Germany

About this study

Food effect will be assessed by comparing the pharmacokinetic (PK) parameters of a single dose of ACT-541468 under fasted (Treatment B) and fed (Treatment C) conditions.

Potential CYP3A4 inhibiting / inducing effects of ACT-541468 will be assessed by comparing the PK parameters of midazolam alone (Treatment A) and midazolam given with a single dose of ACT-541468 (Treatment B) or with multiple doses of ACT-541468 (Treatment D).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

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
  • 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

Treatment and study plan

midazolam

Drug

2 mg/mL oral solution

ACT-541468

Drug

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

Primary outcomes

  1. Maximum plasma concentration (Cmax) of ACT-541468

    Time frame: 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

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

  2. Time to reach Cmax (tmax) of ACT-541468

    Time frame: 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

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

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

    Time frame: 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

    AUC is calculated from time zero to 24 hours post dose

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

    Time frame: 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

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

  5. Maximum plasma concentration (Cmax) of midazolam

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

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

  6. Time to reach Cmax (tmax) of midazolam

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

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

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

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

    AUC is calculated from time zero to 24 hours post dose

  8. Terminal half-life (t1/2) of midazolam

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

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

  9. Maximum plasma concentration (Cmax) of 1-hydroxymidazolam

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

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

  10. Time to reach Cmax (tmax) of 1-hydroxymidazolam

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

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

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

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

    AUC is calculated from time zero to 24 hours post dose

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

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

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

Secondary outcomes

  1. Number of subjects with treatment-emergent adverse events and serious adverse events

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

  2. Maximum plasma concentration (Cmax) of ACT-541468 metabolites

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

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

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

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

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

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

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

Sponsors and collaborators

Lead sponsor

Idorsia Pharmaceuticals Ltd.

Industry

Registry information

Official study title

A Single-center, Open-label Study to Investigate the Food Effect on the Pharmacokinetics of ACT-541468 and the Effect of Single- and Multiple-dose ACT-541468 on the Pharmacokinetics of Midazolam and Its Metabolite 1-Hydroxymidazolam in Healthy Male Subjects

Important dates

Study start
2017
Primary completion
2017
Study completion
2017
First posted
Jan 11, 2017
Registry last updated
Jul 10, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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