Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 1595043 (Double-blind, Randomised, Placebocontrolled, Parallel Group Design) in Healthy Male Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Drug-related Adverse Events (AEs)
Study Overview
Brief Summary
The primary objectives of this trial are to investigate safety and tolerability of BI 1595043 in healthy male subjects following administration of multiple rising doses over 14 days.
Secondary objectives are the exploration of pharmacokinetics (PK) of BI 1595043 after single and multiple dosing.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Masking Description
As this is a Multiple Rising Dose (MRD) trial, blinded individuals will be aware of the current dose level.
All individuals are unblinded regarding the midazolam administration.
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
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), body temperature), 12-lead electrocardiogram (ECG), and clinical laboratory tests
- •Age of 18 to 50 years (inclusive)
- •BMI of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
- •Male subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:
- •Use of adequate contraception, i.e. use of condom (male subjects) plus any of the following methods (female partners): intrauterine device, hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration to the male subject, or barrier method (e.g. diaphragm with spermicide), or surgically sterilised (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy), or postmenopausal, defined as at least 1 year of spontaneous amenorrhea
- •Sexually abstinent
- •Vasectomised (vasectomy at least 1 year prior to enrolment) in combination with a barrier method (i.e. condom) Unprotected sexual intercourse (i.e. without use of condom) with a pregnant female partner and sperm donation is not allowed throughout the study and until 30 days after trial completion
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 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (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
Arms & Interventions
Placebo / Placebo + Midazolam
Placebo matching BI 1595043. Patients included in the placebo arm corresponding to dose group 3, also received Midazolam.
Intervention: Placebo (Drug)
Placebo / Placebo + Midazolam
Placebo matching BI 1595043. Patients included in the placebo arm corresponding to dose group 3, also received Midazolam.
Intervention: Midazolam (Drug)
15 mg BI 1595043
15 milligram (mg) BI 1595043. Dose group 1.
Intervention: BI 1595043 (Drug)
30 mg BI 1595043
30 mg BI 1595043. Dose group 2.
Intervention: BI 1595043 (Drug)
60 mg BI 1595043 + Midazolam
60 mg BI 1595043 + Midazolam. Dose group 3.
Intervention: BI 1595043 (Drug)
60 mg BI 1595043 + Midazolam
60 mg BI 1595043 + Midazolam. Dose group 3.
Intervention: Midazolam (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Drug-related Adverse Events (AEs)
Time Frame: From first drug administration until end of trial examination, up to 30 days.
Percentage of participants with drug-related adverse events (AEs). The causal relationship of AEs to the investigational product was judged by the investigator. The investigator was asked to record a 'yes' if there was, in his/her judgement, a reasonable causal relationship between the investigational product administered and the AE or a 'no' if there was, in his/her judgement, no reasonable causal relationship between the investigational product administered and the AE.
Secondary Outcomes
- Area Under the Concentration-time Curve of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUC0-τ,ss)(0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.)
- Accumulation Ratio Based on Area Under the Concentration-time Curve of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUC0-τ,ss) (RA, AUC)(0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.)
- Maximum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)(0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.)
- Accumulation Ratio Based on Maximum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) (RA, Cmax)(0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.)
- Minimum Measured Concentration of BI 1595043 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss)(0.25 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 and 144 hours after the last dose of BI 1595043.)