Healthy
Conditions
Keywords
Midazolam, Cytochrome P450, Autoimmune disorders, Inflammatory disorders, Sedative-hypnotic
Brief summary
The study will investigate the effect of single dose and multiple doses of M2951 on midazolam Pharmacokinetics (PK) in healthy participants.
Interventions
DRUGM2951
Participants will receive multiple oral doses (twice daily) of M2951 on Day 3 to Day 13 under fed conditions.
DRUGMidazolam
Participants will receive single oral dose of midazolam on Days 1, 3 and 13 under fed conditions.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of 1-hydroxymidazolam | Pre-dose through 24 hours postdose on Days 1, 3 and 13 | — |
| Time to Reach Maximum Plasma Concentration (tmax) of Midazolam and 1-hydroxymidazolam | Pre-dose through 24 hours postdose on Days 1, 3 and 13 | — |
| Apparent Terminal Half-life (t1/2) of Midazolam and 1-hydroxymidazolam | Pre-dose through 24 hours postdose on Days 1, 3 and 13 | — |
| 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 | — |
| Apparent Total Body Clearance (CL/F) of Midazolam | Pre-dose through 24 hours postdose on Days 1, 3 and 13 | — |
| Number of Participants with Clinically Significant Change From Baseline in Laboratory Parameters, Vital Signs and 12-Lead Electrocardiogram (ECG) Findings | 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. |
| 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 | — |
| 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 | — |
| Apparent Volume of Distribution (Vz/F) of Midazolam | Pre-dose through 24 hours postdose on Days 1, 3 and 13 | — |
Countries
Germany
Outcome results
None listed