Healthy
Conditions
Brief summary
The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics and pharmacodynamics of BI 3731579 in healthy volunteers following administration of multiple rising doses per day over 15 days.
Interventions
DRUGMid-dose bid BI 3731579
Day 2 and Day 17: a single mid dose of BI 3731579, with 240 mL of water. Day 4 to Day 16: a double daily mid dose (bid) of BI 3731579 each day, with 240 mL of water.
DRUGPlacebo-matching BI 3731579
Placebo-matching film-coated tablets of BI 3731579 on Day 2 and Day 4 to Day 17, orally, with 240 milliliters (mL) of water.
DRUGMidazolam
Day 1 and Day 17: 75 micrograms (μg) of Midazolam for injection, orally, with 240 mL of water, as a single dose.
DRUGLow-dose bid BI 3731579
Day 2 and Day 17: single low dose of BI 3731579 with 240 milliliters (mL) of water. Day 4 to Day 16: a double daily low dose (bid) of BI 3731579 each day, with 240 mL of water.
DRUGHigh-dose bid BI 3731579
Day 2 and Day 17: single high dose of BI 3731579, with 240 mL of water. Day 4 to Day 16: a double daily high dose (bid) of BI 3731579 each day, with 240 mL of water.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy volunteers 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), respiratory rate (RR) and temperature), 12-lead electrocardiogram (ECG), and clinical laboratory tests 2. Age of 18 to 55 years (inclusive) 3. Body mass index (BMI) of 18.5 to 29.9 kg/m\^2 (inclusive) 4. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial Further inclusion criteria apply.
Exclusion criteria
1. Any finding in the medical examination (including BP, PR, RR, temperature or ECG) deviating from normal and assessed as clinically relevant by the investigator 2. 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 resting pulse rate outside the range of 45 to 90 beats per minute (bpm) 3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 4. Any evidence of a concomitant disease assessed as clinically relevant by the investigator Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Any Treatment-emergent Adverse Event Assessed as Drug-related by the Investigator | From first drug administration on Day 2 until last drug administration on Day 17, plus residual effect period (REP) for each intervention. Up to 19 days. | The occurrence of any treatment-emergent adverse event (TEAE) assessed as drug-related by the investigator is reported as number of participants. The primary endpoint was analyzed without the microdose of midazolam on Day 1, as defined in the statistical analysis plan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 3731579 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) | Up to 408 hours. Detailed timeframe in the description. | Area under the concentration-time curve of BI 3731579 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after its last dose is reported. Timeframe: 0.5 hours before first BI 3731579 administration and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 359.75, 360.25, 360.5, 361, 361.5, 362, 364, 365, 367, 369, 371, 372, 384, and 408 thereafter. |
| Maximum Measured Concentration of BI 3731579 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) | Up to 408 hours. Detailed timeframe in the description. | Maximum measured concentration of BI 3731579 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after its last dose is reported. Timeframe: 0.5 hours before first BI 3731579 administration and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 359.75, 360.25, 360.5, 361, 361.5, 362, 364, 365, 367, 369, 371, 372, 384, and 408 thereafter. |
Countries
Belgium
Participant flow
Recruitment details
Multiple-rising dose (MRD) trial designed as single-blind, randomized within dose groups, and placebo-controlled parallel-group design to investigate safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 3731579 in healthy participants.
Pre-assignment details
All participants were screened for eligibility prior to participation in the trial. The participants attended a specialist site which ensured that they (the participants) strictly met all inclusion and none of the exclusion criteria. The participants were not to be allocated to a treatment group if any of the entry criteria were violated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 39.3 Years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 2 / 30 | 3 / 6 | 8 / 8 | 1 / 8 | 5 / 8 |
| serious Total, serious adverse events | 0 / 30 | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
None listed