Study with healthy volunteers
Conditions
Interventions
Group 1: Cohort A: Single dose 500 mg, multiple doses 500 mg.
Group 2: Cohort B: Single dose 1000 mg, multiple doses 3 x 500 mg.
Group 3: Cohort C: Only multiple dose: 4 x 1000 mg.
Sponsors
Universitätsklinikum Heidelberg
Eligibility
Sex/Gender
All
Age
18 Years to 59 Years
Inclusion criteria
Inclusion criteria: - Males and females of childbearing potential who are willing to use adequate contraception during the treatment and for 15 d after the last administration of imatinib or until EOT, whichever is longer, or women of non-childbearing potential (WNCBP), or individuals who are convincingly sexually abstinent - Participation in a genotyping study (K093) to determine CYP and/or drug transporter genotypes, - Understanding, ability, and willingness to fully comply with trial interventions and restrictions, and - Ability to provide written, personally signed and dated informed consent to participate in the trial, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6, and applicable regulations, prior to any trial-related interventions.
Exclusion criteria
Exclusion criteria: - Clinically significant or relevant abnormalities in the medical history, physical examination, and laboratory evaluation as assessed by the investigator, - Clinically relevant ongoing or clinically relevant history of physical or psychiatric illness as judged by the investigator, - Pregnancy or breast feeding, - Any acute or chronic illness or clinically relevant finding known or expected to modify absorption, distribution, metabolism, or excretion of the Investigational medicinal products (IMPs), - Any known history of severe allergic or anaphylactic reactions to drugs or food or any other clinically significant allergies, - Any known allergies to the IMPs midazolam, metamizole, edoxaban, or imatinib or further ingredients of the trial drugs, - Clinically relevant findings in any investigations at screening (SCR). Minor deviations of laboratory values from the normal range can be acceptable, if judged by the investigator to be of no clinical relevance for this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Geometric mean ratio (GMR) of the area under the plasma concentration-time curve (AUC) extrapolated to infinity (AUC8) and maximal plasma concentration (Cmax) of imatinib at baseline and at presumed maximum cytochrome P450 (CYP) 3A induction by metamizole in cohorts receiving ascending doses of metamizole. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Comparison of midazolam AUC from 2 to 4 h (AUC2-4), AUC8, and Cmax in relation to metamizole total daily dose. - GMR of the AUC8 and Cmax of all probe drugs at baseline and at presumed maximum CYP3A induction by metamizole in cohorts receiving ascending doses of metamizole. - GMR of the AUC8 and Cmax of midazolam at baseline and 2 d after metamizole single-dose administration. - GMR of the AUC8 and Cmax of edoxaban at baseline and with simultaneous intake of a metamizole single dose. - Comparison of the GMRs of AUC8 and Cmax of all probe drugs at baseline and at presumed maximum CYP3A induction by metamizole between men and women. - Urinary excretion of total (glucuronidated and non-glucuronidated) midazolam and total 1’-hydroxymidazolam; plasma concentration-time (c-t) profiles and pharmacokinetic (PK) parameters of midazolam at baseline and under CYP3A induction. - GMR of AUC8 and Cmax of midazolam at baseline and Visit B (imatinib), Visit G (metamizole) and H (metamizole + imatinib). - Descriptive PK parameters of the noncompartmental PK analyses (NCA) of all administered drugs. - Frequency, severity, seriousness, relatedness, expectedness, and outcome of adverse events (AEs) under trial medication. | — |
Countries
Germany
Outcome results
None listed