Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the safety and tolerability of BI 1015550 in healthy male subjects following oral administration of single rising doses. Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality of BI 1015550 after single dosing.
Interventions
DRUGBI 1015550 6 mg
Single rising oral dose
DRUGPlacebo
Single rising oral dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects according to the assessment of the investigator, 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 20 to 45 years (incl.) at screening. * Body Mass Index (BMI) of 18.5 to 25.0 kg/m2 (incl.) at screening. * Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
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) at screening * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance at screening * 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, including but not limited to mood disorders and any history of suicidality * History of relevant orthostatic hypotension, fainting spells, or blackouts * Chronic or relevant acute infections including viral hepatitis, human immunodeficiency virus (HIV) and/or syphilis. (Subject with positive Hepatitis B core antibody will not allowed to participate in this trial) * 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 if 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 on trial days * Alcohol abuse (consumption of more 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 trial medication or during the trial * Inability to comply with dietary regimen of trial site * A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at screening * A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study * Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until three months after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device or hormonal contraceptive since at least two months) In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug-related Adverse Events | From drug administration until end of study, up to 9 days | Number of participants with drug-related adverse events is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Within 3 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 hours after drug administration. | Area under the concentration-time curve of the BI 1015550 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) is presented. |
| Maximum Measured Concentration of the BI 1015550 in Plasma (Cmax) | Within 3 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 hours after drug administration. | Maximum measured concentration of the BI 1015550 in plasma (Cmax) is presented. |
Countries
Japan
Participant flow
Recruitment details
This randomized, parallel, placebo-controlled and double-blind trial tested single dose of BI 1015550 in 2 rising dose groups (12 and 24 mg). Subjects stayed in-house for 2 days (d) after single oral dose of trial drug and the end of trial examination took place 7 to 8 d after trial drug administration.
Pre-assignment details
All subjects were screened for eligibility to participants in the trial. Subjects attended specialist sites which would then ensure that they met all strictly implemented inclusion/exclusion criteria. Subjects were not to be assigned to treatment groups if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Comparator product: Matching placebo. The medication was administrated orally with about 240 milliliter (mL) of water after an overnight fast of at least 10 hours. 2 subjects from BI 1015550 12 milligram (mg) arm and 2 subjects from BI 1015550 24mg arm taking Placebo are combined. | 4 |
| BI 1015550 12mg 2 film-coated tablets with 6mg of BI 1015550 each (12mg total) were administrated as single oral dose with about 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| BI 1015550 24mg 4 film-coated tablets with 6mg of BI 1015550 each (24mg total) were administrated as single oral dose with about 240 mL of water after an overnight fast of at least 10 hours. | 6 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo | BI 1015550 12mg | BI 1015550 24mg | Total |
|---|---|---|---|---|
| Age, Continuous | 27.5 Years STANDARD_DEVIATION 4.7 | 32.8 Years STANDARD_DEVIATION 9.3 | 28.7 Years STANDARD_DEVIATION 8.3 | 29.9 Years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 6 Participants | 6 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 12 |
| other Total, other adverse events | 1 / 4 | 0 / 6 | 0 / 6 | 0 / 12 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 12 |
Outcome results
Primary
Number of Participants With Drug-related Adverse Events
Number of participants with drug-related adverse events is presented.
Time frame: From drug administration until end of study, up to 9 days
Population: Treated set (TS): This subject set included data from all subjects who received at least 1 dose of trial drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Drug-related Adverse Events | 0 Participants |
| BI 1015550 12mg | Number of Participants With Drug-related Adverse Events | 0 Participants |
| BI 1015550 24mg | Number of Participants With Drug-related Adverse Events | 0 Participants |
Secondary
Area Under the Concentration-time Curve of the BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of the BI 1015550 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) is presented.
Time frame: Within 3 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 hours after drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This subject set included data from all subjects from the TS who provided at least 1 secondary pharmacokinetic endpoint (AUC0-inf or Cmax) that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetics, or due to pharmacokinetic non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of the BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 2410 nanomole*hours per Litre (nmol*h/L) | Geometric Coefficient of Variation 20.8 |
| BI 1015550 12mg | Area Under the Concentration-time Curve of the BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 5760 nanomole*hours per Litre (nmol*h/L) | Geometric Coefficient of Variation 21.6 |
Secondary
Maximum Measured Concentration of the BI 1015550 in Plasma (Cmax)
Maximum measured concentration of the BI 1015550 in plasma (Cmax) is presented.
Time frame: Within 3 hours before and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 24, 34, 48, 72, 96, 120 hours after drug administration.
Population: Pharmacokinetic parameter analysis set (PKS): This subject set included data from all subjects from the TS who provided at least 1 secondary pharmacokinetic endpoint (AUC0-inf or Cmax) that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetics, or due to pharmacokinetic non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of the BI 1015550 in Plasma (Cmax) | 449 nanomole per Litre (nmol/L) | Geometric Coefficient of Variation 19.1 |
| BI 1015550 12mg | Maximum Measured Concentration of the BI 1015550 in Plasma (Cmax) | 944 nanomole per Litre (nmol/L) | Geometric Coefficient of Variation 43.5 |