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HealthyPhase 1NCT04697511

Drug-drug Interaction Study of Evobrutinib With Midazolam in Healthy Participants

A Phase 1 study testing Midazolam and M2951 in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The study will investigate the effect of single dose and multiple doses of M2951 on midazolam Pharmacokinetics (PK) in healthy participants. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Midazolam and M2951
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteGermany
Study dates
11 Jan 2021to 25 Feb 2021
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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Participants are overtly healthy as determined by medical evaluation, including no clinically significant abnormality identified on physical examination or laboratory evaluation and no active clinically significant disorder, condition, infection or disease that would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
  • Participants have a body weight within 50.0 and 100.0 kilograms [kg] (inclusive) and body mass index within the range of 19.0 and 30.0 kilograms per square meter [kg/m^2] (inclusive)
  • Other protocol defined inclusion criteria could apply

Who cannot join

  • History or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, as determined by medical evaluation
  • Individuals with diagnosis of hemochromatosis, Wilson´s disease, alpha 1 antitrypsin deficiency, or any other chronic liver disease including Gilbert's disease will be excluded from the study
  • Prior history of cholecystectomy or splenectomy, and any clinically relevant surgery within 6 months prior to Screening
  • History of any malignancy
  • History of chronic or recurrent acute infection or any bacterial, viral, parasitic or fungal infections within 30 days prior to Screening and at any time between Screening and admission, or hospitalization due to infection within 6 months prior to Screening
  • History of shingles within 12 months prior to Screening
Show all 12Show fewer
  • History of drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients; history of serious allergic reactions leading to hospitalization or any other hypersensitivity reaction in general, which may affect the safety of the participant and/or outcome of the study per the Investigator's discretion
  • History of alcoholism or drug abuse within 2 years prior to Screening, or positive for drugs of abuse, nicotine/cotinine or alcohol by the laboratory assays conducted during Screening and Day -1
  • History of residential exposure to tuberculosis, or a positive QuantiFERON® test within 4 weeks prior to or at the time of Screening
  • Administration of live vaccines or live-attenuated virus vaccines within 3 months prior to Screening
  • Moderate or strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A4/5) within 4 weeks prior to the first administration of study intervention
  • Other protocol defined exclusion criteria could apply

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • Nuvisan GmbH

    Neu-Ulm, 89231

Other trials in Germany

About this study

Official title: A Phase I, Single-Sequence, Open-Label, Single- and Multiple-Dose Study of the Effect of Evobrutinib on Midazolam Pharmacokinetics in Healthy Participants

The study will investigate the effect of single dose and multiple doses of M2951 on midazolam Pharmacokinetics (PK) in healthy participants.

Conditions
Healthy
Being tested
Midazolam, M2951
Keywords
Midazolam, Cytochrome P450, Autoimmune disorders, Inflammatory disorders, Sedative-hypnotic
Medical subject headings
Autoimmune Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MidazolamDrug

    Participants will receive single oral dose of midazolam on Days 1, 3 and 13 under fed conditions.

  • M2951Drug

    Also called MSC2364447C, Evobrutinib

    Participants will receive multiple oral doses (twice daily) of M2951 on Day 3 to Day 13 under fed conditions.

Study groups in NCT04697511
Study groupRoleWhat they receive
Midazolam and/or M2951ExperimentalNot described
Receives: Drug: Midazolam; Drug: M2951

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

  2. Maximum Observed Plasma Concentration (Cmax) of Midazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

Secondary outcomes (10)
  1. Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    Measured: Up to Day 14

  2. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) by Severity

    Measured: Up to Day 14

  3. Number of Participants with Clinically Significant Change From Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Findings

    Number of participants with clinically significant change from baseline in laboratory parameters, vital signs and 12- lead ECG findings will be reported.

    Measured: Up to Day 14

  4. Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of 1-hydroxymidazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

  5. Maximum Observed Plasma Concentration (Cmax) of 1-hydroxymidazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

  6. Time to Reach Maximum Plasma Concentration (tmax) of Midazolam and 1-hydroxymidazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

  7. Apparent Terminal Half-life (t1/2) of Midazolam and 1-hydroxymidazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

  8. Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Midazolam and 1-hydroxymidazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

  9. Apparent Total Body Clearance (CL/F) of Midazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

  10. Apparent Volume of Distribution (Vz/F) of Midazolam

    Measured: Pre-dose through 24 hours postdose on Days 1, 3 and 13

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jan 2021
  2. Study start11 Jan 2021
  3. Primary completion25 Feb 2021
  4. Study completion25 Feb 2021

Resources

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
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04697511
Sponsor's protocol ID
MS200527_0063
Other IDs
2020-003668-13
Status last verified
Mar 2021
First submitted
4 Jan 2021
Last updated
23 Mar 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Midazolam and M2951 in people with Healthy, run by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany 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 3 inclusion and 12 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 23 Mar 2021. 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?

Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam (time frame: Pre-dose through 24 hours postdose on Days 1, 3 and 13). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 23 Mar 2021.

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