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
- Registration Number
- NCT05480488
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 18
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) Warfarin * Treatment A - midazolam and warfarin: In the morning of Day 1, subjects will receive a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. * Treatment B - daridorexant, midazolam, and warfarin: Subjects will receive an o.d. oral dose of 50 mg daridorexant in the morning from Day 1 to Day 7 under fasted conditions. In addition, in the morning of Day 1, the oral administration of 50 mg daridorexant will be followed 1 h later by a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. * Treatment C - daridorexant and midazolam: In the morning of Day 1, subjects will receive a single oral dose of 50 mg daridorexant followed 1 h later by a single oral dose of 2 mg midazolam under fasted conditions. • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) Midazolam * Treatment A - midazolam and warfarin: In the morning of Day 1, subjects will receive a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. * Treatment B - daridorexant, midazolam, and warfarin: Subjects will receive an o.d. oral dose of 50 mg daridorexant in the morning from Day 1 to Day 7 under fasted conditions. In addition, in the morning of Day 1, the oral administration of 50 mg daridorexant will be followed 1 h later by a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. * Treatment C - daridorexant and midazolam: In the morning of Day 1, subjects will receive a single oral dose of 50 mg daridorexant followed 1 h later by a single oral dose of 2 mg midazolam under fasted conditions. • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) Daridorexant * Treatment A - midazolam and warfarin: In the morning of Day 1, subjects will receive a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. * Treatment B - daridorexant, midazolam, and warfarin: Subjects will receive an o.d. oral dose of 50 mg daridorexant in the morning from Day 1 to Day 7 under fasted conditions. In addition, in the morning of Day 1, the oral administration of 50 mg daridorexant will be followed 1 h later by a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. * Treatment C - daridorexant and midazolam: In the morning of Day 1, subjects will receive a single oral dose of 50 mg daridorexant followed 1 h later by a single oral dose of 2 mg midazolam under fasted conditions.
- Primary Outcome Measures
Name Time Method AUC0-∞ of S-warfarin 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). Maximum concentration (Cmax) of midazolam and its metabolite 1-OH midazolam 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). Cmax of S-warfarin 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). Time to reach Cmax (tmax) of midazolam and 1-OH midazolam 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). Tmax of S-warfarin 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). Area under the concentration-time curve (AUC) from zero to infinity (AUC0-∞) of midazolam and 1-OH midazolam 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) Terminal elimination half-life (t½) of midazolam and 1-OH midazolam 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). T½ of S-warfarin 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 Outcome Measures
Name Time Method AUC0-144 for international normalized ratio (AUC INR) 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) The maximum effect on INR (INRmax) 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) AUC0-144 for Factor VII (AUC VII) 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) Time to reach maximum effect of INR (t Emax) 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) The maximum effect on Factor VII (VIImax) 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) Time to reach maximum effect of Factor VII (t Emax) 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)
Trial Locations
- Locations (1)
Nuvisan GmbH
🇩🇪Neu-Ulm, Germany