Phase 1
Completed N=50
This Study in Healthy Men Tests How Different Doses of BI 1358894 Are Taken up in the Body and How Well They Are Tolerated. The Study Also Tests How BI 1358894 Affects the Way the Body Breaks Down Midazolam
Healthy
Source: ClinicalTrials.gov NCT03754959 ↗
Enrolled (actual)
50
Serious AEs
0.0%
Results posted
Apr 2025
Primary outcomePrimary: Number of Subjects With On-treatment Drug-related Adverse Events (AEs). — 0; 1; 4; 4 Participants
Summary
The primary objective of the trial is to investigate the safety and tolerability of BI 1358894 in healthy male subjects following oral administration of multiple rising doses over 14 days.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With On-treatment Drug-related Adverse Events (AEs). |
0; 1; 4; 4; 3; 4 | — |
| SECONDARY Area Under the Concentration-time Curve of BI 1358894 in Plasma Over a Time Interval 0 to 24 h After Administration of the First Dose |
801; 1570; 2690; 5520; 8200 | — |
| SECONDARY Maximum Measured Concentration of BI 1358894 in Plasma |
78.8; 152; 217; 491; 634 | — |
| SECONDARY Area Under the Concentration-time Curve of BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ |
2070; 3520; 5890; 12600; 18900 | — |
| SECONDARY Maximum Measured Concentration of BI 1358894 in Plasma at Steady State Over a Uniform Dosing Interval τ |
138; 225; 383; 843; 1150 | — |
| SECONDARY Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (Day 1) |
2960; 3630; 3120; 2810; 3360; 2480 | — |
| SECONDARY Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (Day 14) |
3200; 4450; 3360; 3440; 3480; 2460 | — |
| SECONDARY Maximum Measured Concentration of Midazolam in Plasma (Day 1) |
913; 1090; 1130; 920; 1150; 812 | — |
| SECONDARY Maximum Measured Concentration of Midazolam in Plasma (Day 14) |
887; 1180; 1070; 1090; 985; 722 | — |
Eligibility Criteria
Inclusion Criteria
- Healthy male subjects according to the investigator's assessment, 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 45 years (incl.)
- Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
- Willingness to comply with contraception requirements. Subjects who are sexually active must use adequate contraception with their female partner throughout the study and until one month after the last administration of trial medication. Adequate methods are:
- Sexual abstinence or
- A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) or
- Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner or
- The use of condoms, if the female partner uses an adequate contraception method in addition, e.g., intrauterine device (IUD), hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g. diaphragm with spermicide) Unprotected sexual intercourse with a female partner is not allowed throughout the study and until one month after the last administration of trial medication.
Exclusion Criteria
- Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR) or Electrocardiogram (ECG)) is deviating from normal and judged 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 beats per minute (bpm)
- C-Reactive Protein > upper limit of normal (ULN), erythrocyte sedimentation rate (ESR) ≥15 millimeters/h, liver or kidney parameter above ULN, or any other laboratory value outside the reference range that the investigator considers to be of clinical relevance
- Positive or missing faecal occult blood test (retest allowed)
- Positive testing for faecal calprotectin (retest allowed)
- Any evidence of a concomitant disease judged as clinically relevant by the investigator
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and 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
- Chronic or relevant acute infections
- History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
- Use of drugs within 30 days prior to administration of trial medication that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
- Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
- Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
- Inability to refrain from smoking during in-house confinement
- Alcohol abuse (consumption of more than 30 g per day)
- Drug abuse or positive drug screening
- Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
- Intention to perform excessive physical activities within one week prior to administration of
Data sourced from ClinicalTrials.gov (NCT03754959). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.