Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the effect of food on the pharmacokinetics of the oral tablet formulation of BI 1015550 by investigating the relative bioavailability of TF1 under fed and fasted conditions. The assessment of safety and tolerability will be an additional objective of this part.
Interventions
DRUGBI 1015550
Single dose of BI 1015550 4x6 mg (24 mg) tablets under fed or fasted condition
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 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 18 to 55 years (incl.) * 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 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 45 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 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) * 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 signs of suicidality (ideation as well as behavior) in the past * 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 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 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 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 Electrocardiogram (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 two month after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device, hormonal contraceptive since at least two month)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Pharmacokinetic samples were collected at 3:00 (hours:minutes) before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 120:00 (hours:minutes) after drug administration on day 1. | AUC0-tz, area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 to the last quantifiable data point. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Adjusted mean estimates and their difference on log-scale were back-transformed to the original scale. |
| Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | Pharmacokinetic samples were collected at 3:00 (hours:minutes) before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 120:00 (hours:minutes) after drug administration on day 1. | Cmax, maximum measured concentration of BI 1015550 in plasma. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Adjusted mean estimates and their difference on log-scale were back-transformed to the original scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | Pharmacokinetic samples were collected at 3:00 (hours:minutes) before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 120:00 (hours:minutes) after drug administration on day 1. | AUC0-inf, area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 extrapolated to infinity. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Adjusted mean estimates and their difference on log-scale were back-transformed to the original scale. |
Countries
Germany
Participant flow
Recruitment details
This was a phase I, open-label, randomised, single dose, two-period, two-sequence crossover trial performed in healthy subjects.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist site which would then ensure that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial treatment if any one of the specific entry criteria were not met
Participants by arm
| Arm | Count |
|---|---|
| BI 1015550 24 Milligrams (mg) Fed / BI 1015550 24 mg Fast Subjects were treated orally in period 1 with single dose of BI 1015550 4x6 mg (24 mg) tablets under fed condition, followed in period 2 with 4x6 mg (24 mg) of BI 1015550 tablets under fasted condition, each treatment with 240 milliliter (mL) water, separated by a wash-out period of at least 7 days between drug administrations. | 6 |
| BI 1015550 24 mg Fast / BI 1015550 24 mg Fed Subjects were treated orally in period 1 with single dose of BI 1015550 4x6 mg (24 mg) tablets under fasted condition, followed in period 2 with 4x6 mg (24 mg) of BI 1015550 tablets under fed condition, each treatment with 240 mL water, separated by a wash-out period of at least 7 days between drug administrations. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | BI 1015550 24 mg Fast / BI 1015550 24 mg Fed | Total | BI 1015550 24 Milligrams (mg) Fed / BI 1015550 24 mg Fast |
|---|---|---|---|
| Age, Continuous | 40.5 Years STANDARD_DEVIATION 13.1 | 43.3 Years STANDARD_DEVIATION 10.8 | 46.2 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 12 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 1 / 11 | 5 / 12 | 6 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
AUC0-tz, area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 to the last quantifiable data point. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Adjusted mean estimates and their difference on log-scale were back-transformed to the original scale.
Time frame: Pharmacokinetic samples were collected at 3:00 (hours:minutes) before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 120:00 (hours:minutes) after drug administration on day 1.
Population: Pharmacokinetic (PK) set (PKS):The PKS included all subjects in the Treated Set (TS) who provided at least one primary or secondary PK parameter that was not excluded due to important protocol violations relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 24 mg fed (Test, T) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 4164.32 nanomole*hours/Liter (nmol*h/L) |
| BI 1015550 24 mg fast (Reference, R) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 4057.42 nanomole*hours/Liter (nmol*h/L) |
Comparison: The analysis of variance (ANOVA) model on a logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. No hypothesis was tested and no acceptance range was specified. This was an intra-individual assessment and actually only 12 subjects were analyzed.90% CI: [98.31, 107.15]
Primary
Maximum Measured Concentration of BI 1015550 in Plasma (Cmax)
Cmax, maximum measured concentration of BI 1015550 in plasma. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Adjusted mean estimates and their difference on log-scale were back-transformed to the original scale.
Time frame: Pharmacokinetic samples were collected at 3:00 (hours:minutes) before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 120:00 (hours:minutes) after drug administration on day 1.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 24 mg fed (Test, T) | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 404.34 nanomole/Liter (nmol/L) |
| BI 1015550 24 mg fast (Reference, R) | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 511.29 nanomole/Liter (nmol/L) |
Comparison: The analysis of variance (ANOVA) model on a logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. No hypothesis was tested and no acceptance range was specified. This was an intra-individual assessment and actually only 12 subjects were analyzed.90% CI: [69.96, 89.4]
Secondary
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
AUC0-inf, area under the concentration-time curve of BI 1015550 in plasma over the time interval from 0 extrapolated to infinity. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. The model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. Adjusted mean estimates and their difference on log-scale were back-transformed to the original scale.
Time frame: Pharmacokinetic samples were collected at 3:00 (hours:minutes) before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00 and 120:00 (hours:minutes) after drug administration on day 1.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 24 mg fed (Test, T) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 4232.24 nmol*h/L |
| BI 1015550 24 mg fast (Reference, R) | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | 4131.48 nmol*h/L |
Comparison: The analysis of variance (ANOVA) model on a logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed. No hypothesis was tested and no acceptance range was specified. This was an intra-individual assessment and actually only 12 subjects were analyzed.90% CI: [97.8, 107.3]