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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04697511
• Other study ID #: MS200527_0063
• Secondary ID: 2020-003668-13
• Status: Completed
• Phase: Phase 1
• Start date: January 11, 2021
• Est. completion date: February 25, 2021

Study information

• Verified date: March 2021
• Source: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 25, 2021
• Est. primary completion date: February 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Midazolam
Participants will receive single oral dose of midazolam on Days 1, 3 and 13 under fed conditions.
• M2951
Participants will receive multiple oral doses (twice daily) of M2951 on Day 3 to Day 13 under fed conditions.

Locations

Country	Name	City	State
Germany	Nuvisan GmbH	Neu-Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Maximum Observed Plasma Concentration (Cmax) of Midazolam		Pre-dose through 24 hours postdose on Days 1, 3 and 13
Secondary	Number of Participants with Treatment-Emergent Adverse Events (TEAEs)		Up to Day 14
Secondary	Number of Participants with Treatment-Emergent Adverse Events (TEAEs) by Severity		Up to Day 14
Secondary	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.	Up to Day 14
Secondary	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
Secondary	Maximum Observed Plasma Concentration (Cmax) of 1-hydroxymidazolam		Pre-dose through 24 hours postdose on Days 1, 3 and 13
Secondary	Time to Reach Maximum Plasma Concentration (tmax) of Midazolam and 1-hydroxymidazolam		Pre-dose through 24 hours postdose on Days 1, 3 and 13
Secondary	Apparent Terminal Half-life (t1/2) of Midazolam and 1-hydroxymidazolam		Pre-dose through 24 hours postdose on Days 1, 3 and 13
Secondary	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Midazolam and 1-hydroxymidazolam		Pre-dose through 24 hours postdose on Days 1, 3 and 13
Secondary	Apparent Total Body Clearance (CL/F) of Midazolam		Pre-dose through 24 hours postdose on Days 1, 3 and 13
Secondary	Apparent Volume of Distribution (Vz/F) of Midazolam		Pre-dose through 24 hours postdose on Days 1, 3 and 13

External Links

•   Trial Awareness and Transparency website