A Study in Healthy Men to Test Whether BI 1015550 Influences the Amount of Midazolam in the Blood

• BI 1015550 (Drug), also known as Nerandomilast, JASCAYD®: BI 1015550
• midazolam (Drug): midazolam

Primary outcomes

• Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) [Midazolam (R): Within 3 hours prior to midazolam administration and up to 24 hours after midazolam administration, in period 1. BI 101550 + midazolam (T): 313 hours prior and up to 24 hours after BI 1015550 + midazolam administration, in period 2.]: Area under the concentration-time curve of midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Detailed timeframe: For midazolam (R): Within 3 hours prior to midazolam administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after midazolam administration in period 1. For BI + midazolam (T): 313 hours prior to administration of BI 1015550 + midazolam, at BI 1015550 + midazolam administration (0 hour) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after administration of BI 1015550 + midazolam in period 2.
• Maximum Measured Concentration of Midazolam in Plasma (Cmax) [Midazolam (R): Within 3 hours prior to midazolam administration and up to 24 hours after midazolam administration, in period 1. BI 101550 + midazolam (T): 313 hours prior and up to 24 hours after BI 1015550 + midazolam administration, in period 2.]: Maximum measured concentration of midazolam in plasma (Cmax). Detailed timeframe: For midazolam (R): Within 3 hours prior to midazolam administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after midazolam administration in period 1. For BI + midazolam (T): 313 hours prior to administration of BI 1015550 + midazolam, at BI 1015550 + midazolam administration (0 hour) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after administration of BI 1015550 + midazolam in period 2.

Secondary outcomes

• Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) [Midazolam (R): Within 3 hours prior to midazolam administration and up to 24 hours after midazolam administration, in period 1. BI 101550 + midazolam (T): 313 hours prior and up to 24 hours after BI 1015550 + midazolam administration, in period 2.]: Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Detailed timeframe: For midazolam (R): Within 3 hours prior to midazolam administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after midazolam administration in period 1. For BI + midazolam (T): 313 hours prior to administration of BI 1015550 + midazolam, at BI 1015550 + midazolam administration (0 hour) and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours after administration of BI 1015550 + midazolam in period 2.

Sex: Male, ages: 18 Years to 55 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy male subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
* Age of 18 to 55 years (inclusive)
* Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
* Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial

Exclusion Criteria:

* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
* Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
* Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
* Any evidence of a concomitant disease assessed as clinically relevant by the investigator
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
* Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
* History of relevant orthostatic hypotension, fainting spells, or blackouts
* Further exclusion criteria apply

Participant flow

Outcome results

• Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Primary), Geometric least squares mean, Hours * nanomol per liter (h*nmol/L): Midazolam (R) 75.1 +/- NA; BI 1015550 + Midazolam (T) 69.3 +/- NA
• Maximum Measured Concentration of Midazolam in Plasma (Cmax) (Primary), Geometric least squares mean, Nanomol per Liter (nmol/L): Midazolam (R) 28.0 +/- NA; BI 1015550 + Midazolam (T) 21.8 +/- NA
• Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (Secondary), Geometric least squares mean, Hours * nanomol per liter (h*nmol/L): Midazolam (R) 80.8 +/- NA; BI 1015550 + Midazolam (T) 72.6 +/- NA

Adverse events

Time frame: For Midazolam: At midazolam administration, plus 12 hours of residual effect period (REP), up to 12 hours. For BI 101550 and BI 101550 + Midazolam: From first drug administration until last drug administration, plus REP of 7 days, up to 21 days.

Other adverse events by term

• Study Protocol (PDF, 2022-09-23)
• Statistical Analysis Plan (PDF, 2023-01-16)