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

Healthy Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05480488
• Other study ID #: ID-078-126
• Status: Completed
• Phase: Phase 1
• Start date: August 23, 2022
• Est. completion date: October 6, 2022

Study information

• Verified date: November 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 6, 2022
• Est. primary completion date: September 23, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Midazolam
Subjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C).
• Warfarin
Subjects will receive a single oral dose of 25 mg warfarin (Treatment A and B).
• Daridorexant
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.

Locations

Country	Name	City	State
Germany	Nuvisan GmbH	Neu-Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	Area under the concentration-time curve (AUC) from zero to infinity (AUC0-8) 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)
Primary	AUC0-8 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).
Primary	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).
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)