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

NCT04697511 | Completed Phase 1

• 2 other identifiers: MS200527_00632020-003668-13
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Midazolam; Cytochrome P450; Autoimmune disorders; Inflammatory disorders; Sedative-hypnotic

Outcome Measures

Primary Outcomes (2)

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

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

• Maximum Observed Plasma Concentration (Cmax) of Midazolam

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

Secondary Outcomes (10)

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

  Up to Day 14

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

  Up to Day 14

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

  Up to Day 14

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

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

• Maximum Observed Plasma Concentration (Cmax) of 1-hydroxymidazolam

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

Study Arms (1)

Midazolam and/or M2951

EXPERIMENTAL

Drug: Midazolam; Drug: M2951

Interventions

Midazolam DRUG

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

Midazolam and/or M2951

M2951 DRUG

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

Also known as: MSC2364447C, Evobrutinib

Midazolam and/or M2951

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Location

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

Midazolam; evobrutinib

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 6, 2021
• Study Start: January 11, 2021
• Primary Completion: February 25, 2021
• Study Completion: February 25, 2021
• Last Updated: March 23, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)