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OpenTrials
Completed

NCT Number: NCT04697511

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

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

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

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

  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

midazolam

Drug

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

M2951

Drug

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

Other names: MSC2364447C, Evobrutinib

Primary outcomes

  1. 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

  2. Maximum Observed Plasma Concentration (Cmax) of Midazolam

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

Secondary outcomes

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

    Time frame: Up to Day 14

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

    Time frame: 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

    Time frame: Up to Day 14

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

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

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

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

    Time frame: 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

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

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

    Time frame: 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

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

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

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

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

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

Sponsors and collaborators

Lead sponsor

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2021
Study completion
2021
First posted
Jan 6, 2021
Registry last updated
Mar 23, 2021

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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