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Completed

NCT Number: NCT05480488

A Study to Examine the Effect of Daridorexant on the Way the Body Absorbs, Distributes, and Gets Rid of Midazolam and Warfarin in Healthy Male Subjects

A study to examine the effect of daridorexant on the way the body absorbs, distributes, and gets rid of midazolam and warfarin in healthy male subjects

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Key information

Conditions

Healthy

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
  • Healthy male subject aged between 18 and 45 years (inclusive) at Screening.

Exclusion criteria

  • Known hypersensitivity to daridorexant, midazolam, warfarin, or treatments of the same class, or any of their excipients.
  • Any history of hemorrhagic disease, whether or not hereditary.
  • Any history of complications with bleeding after surgery or tooth extractions and/or frequent nasal, hemorrhoidal, or gingival bleeding.
  • Activated partial thromboplastin time (aPTT) > 40 sec and/or international normalized ratio (INR) > 1.15 at Screening.
  • Platelet count < 150 or >400 x 10^9/L at Screening.
  • Clinically relevant findings on the physical examination at Screening.
  • Clinically relevant abnormalities on 12-lead ECG, measured after 5 min in the supine position at Screening.
  • Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry) at Screening.

Treatment and study plan

midazolam

Drug

Subjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C).

Warfarin

Drug

Subjects will receive a single oral dose of 25 mg warfarin (Treatment A and B).

Daridorexant

Drug

Subjects will receive an o.d. oral dose of 50 mg daridorexant from Day 1 to Day 7 of Treatment B and a single oral dose of 50 mg daridorexant on Day 1 of Treatment C.

Primary outcomes

  1. Maximum concentration (Cmax) of midazolam and its metabolite 1-OH midazolam

    Time frame: Blood samples for pharmacokinetic analyses of midazolam will be taken at various time points from Day 1 to 2 of Treatment Period A, from Day 1 to 2 of Treatment Period B, and from Day 1 to 2 of Treatment Period C (total duration: 6 days).

  2. Cmax of S-warfarin

    Time frame: Blood samples for pharmacokinetic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days).

  3. Time to reach Cmax (tmax) of midazolam and 1-OH midazolam

    Time frame: Blood samples for pharmacokinetic analyses of midazolam will be taken at various time points from Day 1 to 2 of Treatment Period A, from Day 1 to 2 of Treatment Period B, and from Day 1 to 2 of Treatment Period C (total duration: 6 days).

  4. Tmax of S-warfarin

    Time frame: Blood samples for pharmacokinetic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days).

  5. Area under the concentration-time curve (AUC) from zero to infinity (AUC0-∞) of midazolam and 1-OH midazolam

    Time frame: Blood samples for pharmacokinetic analyses of midazolam will be taken at various time points from Day 1 to 2 of Treatment Period A, from Day 1 to 2 of Treatment Period B, and from Day 1 to 2 of Treatment Period C (total duration: 6 days)

  6. AUC0-∞ of S-warfarin

    Time frame: Blood samples for pharmacokinetic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days).

  7. Terminal elimination half-life (t½) of midazolam and 1-OH midazolam

    Time frame: Blood samples for pharmacokinetic analyses of midazolam will be taken at various time points from Day 1 to 2 of Treatment Period A, from Day 1 to 2 of Treatment Period B, and from Day 1 to 2 of Treatment Period C (total duration: 6 days).

  8. T½ of S-warfarin

    Time frame: Blood samples for pharmacokinetic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days).

Secondary outcomes

  1. AUC0-144 for international normalized ratio (AUC INR)

    Time frame: Blood samples for pharmacodynamic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days)

  2. The maximum effect on INR (INRmax)

    Time frame: Blood samples for pharmacodynamic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days)

  3. Time to reach maximum effect of INR (t Emax)

    Time frame: Blood samples for pharmacodynamic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days)

  4. AUC0-144 for Factor VII (AUC VII)

    Time frame: Blood samples for pharmacodynamic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days)

  5. The maximum effect on Factor VII (VIImax)

    Time frame: Blood samples for pharmacodynamic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days)

  6. Time to reach maximum effect of Factor VII (t Emax)

    Time frame: Blood samples for pharmacodynamic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days)

Sponsors and collaborators

Lead sponsor

Idorsia Pharmaceuticals Ltd.

Industry

Registry information

Official study title

A Single-center, Open-label Study to Investigate the Effect of Single- and Multiple-dose Daridorexant on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam, and the Effect of Single-dose Daridorexant on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects

Important dates

Study start
2022
Primary completion
2022
Study completion
2022
First posted
Jul 29, 2022
Registry last updated
Nov 8, 2022

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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