HealthyPhase 1NCT05480488
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 Phase 1 study testing Midazolam, Warfarin and Daridorexant in people with Healthy, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
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 Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Midazolam, Warfarin and Daridorexant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteGermany
- Study dates
- 23 Aug 2022to 6 Oct 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Conditions
- Healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Subjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C).
WarfarinDrug
Subjects will receive a single oral dose of 25 mg warfarin (Treatment A and B).
DaridorexantDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) | Other | * 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. Receives: Drug: Midazolam; Drug: Warfarin; Drug: Daridorexant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum concentration (Cmax) of midazolam and its metabolite 1-OH midazolam
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
AUC0-∞ of S-warfarin
Measured: 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).
Terminal elimination half-life (t½) of midazolam and 1-OH midazolam
Measured: 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
Measured: 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 (6)
AUC0-144 for international normalized ratio (AUC INR)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2022
- Study start23 Aug 2022
- Primary completion23 Sep 2022
- Study completion6 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- This is a prospective, open-label, fixed-sequence Phase 1 study.
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Idosia Pharmaceuticals Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05480488
- Sponsor's protocol ID
- ID-078-126
- Status last verified
- Nov 2022
- First submitted
- 27 Jul 2022
- Last updated
- 8 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zenklusen I, Dingemanse J, Reh C, Gehin M, Kaufmann P. Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects. Drugs R D. 2024 Mar;24(1):97-108. doi: 10.1007/s40268-024-00456-8. Epub 2024 Mar 13.
PubMed 38472696
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05480488
- Acronym / sponsor ID
- ID-078-126
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 23 Aug 2022 (actual)
- Primary completion
- 23 Sep 2022 (actual)
- Study completion
- 6 Oct 2022 (actual)
- First posted
- 29 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective, open-label, fixed-sequence Phase 1 study.
| Arm | Type | Receives |
|---|---|---|
| • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) | Other | Drug: Midazolam, Drug: Warfarin, Drug: 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MidazolamSubjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C). | Drug | • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) |
| WarfarinSubjects will receive a single oral dose of 25 mg warfarin (Treatment A and B). | Drug | • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) |
| DaridorexantSubjects 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. | Drug | • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) |
Primary outcome
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).
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).
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).
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).
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)
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).
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).
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).
6 secondary outcomes
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)
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)
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)
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)
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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Derived from this study: PubMed 38472696Zenklusen I, Dingemanse J, Reh C, Gehin M, Kaufmann P. Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects. Drugs R D. 2024 Mar;24(1):97-108. doi: 10.1007/s40268-024-00456-8. Epub 2024 Mar 13.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Idosia Pharmaceuticals Ltd
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Midazolam, Warfarin and Daridorexant in people with Healthy, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05480488, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.