Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the safety and tolerability of BI 1323495 in healthy male subjects following oral administration of single rising doses. Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality and pharmacodynamics (PD) of BI 1323495 after single dosing and the assessment of the PK/PD relationship.
Interventions
DRUGBI 1323495
Low strength tablet
DRUGPlacebo
Placebo to low strength tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 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 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
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 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 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 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 specified 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 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 In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Drug-related Adverse Events | From drug administration until end of trial, up to 15 days. | Percentage of participants with drug-related adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1 hour (h) before drug administration and 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 24, 34, 48, 72 and 96 h and additionally 4.75, 5.5, 6.5, 7.5 h for dose group 1/2/3 and 0.333, 0.667, 1.5, 5 h for dose group 4/5/6/7/8 after drug administration. | Area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) after single oral administration of BI 1323495. |
| Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 1 hour (h) before drug administration and 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 24, 34, 48, 72 and 96 h and additionally 4.75, 5.5, 6.5, 7.5 h for dose group 1/2/3 and 0.333, 0.667, 1.5, 5 h for dose group 4/5/6/7/8 after drug administration. | Maximum measured concentration of BI 1323495 in plasma (Cmax) after single oral administration of BI 1323495. |
Countries
Germany
Participant flow
Recruitment details
This single-rising dose trial was designed as single-blind, partially randomised, and placebo-controlled within parallel dose groups.
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 strictly implemented inclusion/exclusion criteria. Participants were not to be assigned to treatment groups if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching BI 1323495 Participants were orally administered single dose of placebo matching to BI 1323495 film-coated tablets with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h). | 15 |
| BI 1323495 Dose Group 1 Participants were orally administered single dose of BI 1323495 dose group 1 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| BI 1323495 Dose Group 2 Participants were orally administered single dose of BI 1323495 dose group 2 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| BI 1323495 Dose Group 3 Participants were orally administered single dose of BI 1323495 dose group 3 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| BI 1323495 Dose Group 4 Participants were orally administered single dose of BI 1323495 dose group 4 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| BI 1323495 Dose Group 5 Participants were orally administered single dose of BI 1323495 dose group 5 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| BI 1323495 Dose Group 6 Participants were orally administered single dose of BI 1323495 dose group 6 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| BI 1323495 Dose Group 7 Participants were orally administered single dose of BI 1323495 dose group 7 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| BI 1323495 Dose Group 8 Participants were orally administered single dose of BI 1323495 dose group 8 film-coated tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| Total | 63 |
Baseline characteristics
| Characteristic | Total | Placebo Matching BI 1323495 | BI 1323495 Dose Group 1 | BI 1323495 Dose Group 2 | BI 1323495 Dose Group 3 | BI 1323495 Dose Group 4 | BI 1323495 Dose Group 5 | BI 1323495 Dose Group 6 | BI 1323495 Dose Group 7 | BI 1323495 Dose Group 8 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 30.9 Years STANDARD_DEVIATION 6.6 | 28.9 Years STANDARD_DEVIATION 6 | 28.0 Years STANDARD_DEVIATION 7.6 | 31.5 Years STANDARD_DEVIATION 6.4 | 29.8 Years STANDARD_DEVIATION 8.9 | 34.3 Years STANDARD_DEVIATION 5.4 | 33.7 Years STANDARD_DEVIATION 8.6 | 34.3 Years STANDARD_DEVIATION 6.5 | 30.8 Years STANDARD_DEVIATION 4.1 | 29.5 Years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 15 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 63 Participants | 15 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 63 Participants | 15 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 48 |
| other Total, other adverse events | 2 / 15 | 3 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 3 / 6 | 2 / 6 | 16 / 48 |
| serious Total, serious adverse events | 0 / 15 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 48 |
Outcome results
Primary
Percentage of Participants With Drug-related Adverse Events
Percentage of participants with drug-related adverse events.
Time frame: From drug administration until end of trial, up to 15 days.
Population: Treated set (TS): This subject set included all subjects who were documented to have received at least 1 dose of trial drug. It was used for analysis of safety, demographic data, and baseline characteristics, as well as for the description of biomarkers.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching BI 1323495 | Percentage of Participants With Drug-related Adverse Events | 6.7 Percentage of participants |
| BI 1323495 Dose Group 1 | Percentage of Participants With Drug-related Adverse Events | 50.0 Percentage of participants |
| BI 1323495 Dose Group 2 | Percentage of Participants With Drug-related Adverse Events | 33.3 Percentage of participants |
| BI 1323495 Dose Group 3 | Percentage of Participants With Drug-related Adverse Events | 0.0 Percentage of participants |
| BI 1323495 Dose Group 4 | Percentage of Participants With Drug-related Adverse Events | 16.7 Percentage of participants |
| BI 1323495 Dose Group 5 | Percentage of Participants With Drug-related Adverse Events | 0.0 Percentage of participants |
| BI 1323495 Dose Group 6 | Percentage of Participants With Drug-related Adverse Events | 16.7 Percentage of participants |
| BI 1323495 Dose Group 7 | Percentage of Participants With Drug-related Adverse Events | 50.0 Percentage of participants |
| BI 1323495 Dose Group 8 | Percentage of Participants With Drug-related Adverse Events | 16.7 Percentage of participants |
Secondary
Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) after single oral administration of BI 1323495.
Time frame: 1 hour (h) before drug administration and 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 24, 34, 48, 72 and 96 h and additionally 4.75, 5.5, 6.5, 7.5 h for dose group 1/2/3 and 0.333, 0.667, 1.5, 5 h for dose group 4/5/6/7/8 after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): This subject set included all subjects from the TS receiving BI 1323495 who provided at least 1 secondary PK parameter that was not excluded (due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 1323495 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 143 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 102 |
| BI 1323495 Dose Group 1 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 883 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 118 |
| BI 1323495 Dose Group 2 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 824 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 77.7 |
| BI 1323495 Dose Group 3 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2360 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 73.5 |
| BI 1323495 Dose Group 4 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3710 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 69.4 |
| BI 1323495 Dose Group 5 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3120 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 140 |
| BI 1323495 Dose Group 6 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 1780 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 102 |
| BI 1323495 Dose Group 7 | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3820 nanomole (nmol)*hours (h) /Liter (L) | Geometric Coefficient of Variation 71.9 |
Comparison: The basic model for the investigation of dose proportionality was a power model that described the functional relationship between the dose and PK endpoints.95% CI: [0.5006, 0.8914]
Comparison: The basic model for the investigation of dose proportionality was a power model that described the functional relationship between the dose and PK endpoints.95% CI: [0.6764, 1.1724]
Secondary
Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)
Maximum measured concentration of BI 1323495 in plasma (Cmax) after single oral administration of BI 1323495.
Time frame: 1 hour (h) before drug administration and 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 24, 34, 48, 72 and 96 h and additionally 4.75, 5.5, 6.5, 7.5 h for dose group 1/2/3 and 0.333, 0.667, 1.5, 5 h for dose group 4/5/6/7/8 after drug administration.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matching BI 1323495 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 10.5 nmol/L | Geometric Coefficient of Variation 66.3 |
| BI 1323495 Dose Group 1 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 59.4 nmol/L | Geometric Coefficient of Variation 147 |
| BI 1323495 Dose Group 2 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 145.0 nmol/L | Geometric Coefficient of Variation 74.8 |
| BI 1323495 Dose Group 3 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 229.0 nmol/L | Geometric Coefficient of Variation 127 |
| BI 1323495 Dose Group 4 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 179.0 nmol/L | Geometric Coefficient of Variation 152 |
| BI 1323495 Dose Group 5 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 136.0 nmol/L | Geometric Coefficient of Variation 74.2 |
| BI 1323495 Dose Group 6 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 195.0 nmol/L | Geometric Coefficient of Variation 90.8 |
| BI 1323495 Dose Group 7 | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 195.0 nmol/L | Geometric Coefficient of Variation 90.8 |
Comparison: The basic model for the investigation of dose proportionality was a power model that described the functional relationship between the dose and PK endpoints.95% CI: [0.4556, 0.851]
Comparison: The basic model for the investigation of dose proportionality was a power model that described the functional relationship between the dose and PK endpoints.95% CI: [0.5929, 1.1242]