Healthy
Conditions
Brief summary
The main objective of this trial is to assess the effect of food on the pharmacokinetics of an oral tablet formulation of BI 1323495 by investigating the relative bioavailability following single dose administration under fed and fasted conditions.
Interventions
DRUGBI 1323495,
single oral doses
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
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, as 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 (inclusive) * Body Mass Index (BMI) of 18.5 to 29.9 kg/m\^2 (inclusive) * 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)) deviating from normal and assessed 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) * 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 * 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 of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation) * Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point | Within 2 hours before and then 20 minutes (min), 40 min, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48, 72 and 96 hours after drug administration | Area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for sequence, subjects nested within sequences, period, and treatment. Confidence intervals were calculated based on the residual error from the ANOVA. |
| Maximum Measured Concentration of BI 1323495 in Plasma | Within 2 hours before and then 20 minutes (min), 40 min, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48, 72 and 96 hours after drug administration | Maximum measured concentration of BI 1323495 in plasma (Cmax). The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for sequence, subjects nested within sequences, period, and treatment. Confidence intervals were calculated based on the residual error from the ANOVA. |
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 | Within 2 hours before and then 20 minutes (min), 40 min, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48, 72 and 96 hours after drug administration | Area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for sequence, subjects nested within sequences, period, and treatment. Confidence intervals were calculated based on the residual error from the ANOVA. |
Countries
Germany
Participant flow
Recruitment details
The trial was performed as a randomized, open-label, two-way crossover trial in healthy male subjects in order to compare the test treatment (T) with the reference treatment (R). The treatments were 2 single oral doses of BI 1323495, administered under fasted (R) and fed (T) conditions and separated by a washout period of at least 6 days.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 100 Milligram (mg) of BI1323495 Fasted-100 mg of BI1323495 Fed 2 film-coated tablets with 50 mg of BI 1323495 (total: 100 mg) was administered as a single oral dose with 240 milliliter (mL) of water after an overnight fast of at least 10 hours (h) as reference treatment (R) followed by a wash-out period of at least 6 days followed by 2 film-coated tablets with 50 mg of BI 1323495 (total: 100mg) administered as a single oral dose with 240 mL of water 30 minutes after a high-fat, high-calorie meal (fed condition) as a test treatment (T). | 6 |
| 100 mg of BI1323495 Fed-100 mg of BI1323495 Fasted 2 film-coated tablets with 50 mg of BI 1323495 (total: 100 mg) was administered as a single oral dose with 240 milliliter (mL) of water 30 minutes after a high-fat, high-calorie meal as test treatment (T) followed by a wash-out period of at least 6 days followed by 2 film-coated tablets with 50 mg of BI 1323495 (total: 100mg) administered as a single oral dose with 240 mL of water after an overnight fast of at least 10 h as a reference treatment (R). | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 (P1) + Washout | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | 100 mg of BI1323495 Fed-100 mg of BI1323495 Fasted | Total | 100 Milligram (mg) of BI1323495 Fasted-100 mg of BI1323495 Fed |
|---|---|---|---|
| Age, Continuous | 32.3 Years STANDARD_DEVIATION 7.4 | 32.3 Years STANDARD_DEVIATION 6.2 | 32.2 Years STANDARD_DEVIATION 5.4 |
| 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 |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 2 / 11 | 3 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point
Area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for sequence, subjects nested within sequences, period, and treatment. Confidence intervals were calculated based on the residual error from the ANOVA.
Time frame: Within 2 hours before and then 20 minutes (min), 40 min, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48, 72 and 96 hours after drug administration
Population: Pharmacokinetic parameter analysis set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK endpoint 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) |
|---|---|---|
| BI 1323495 Fed (T) | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point | NA nanomol (nmol) * hours (h) / Litre (L) |
| BI 1323495 Fasted (R) | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point | NA nanomol (nmol) * hours (h) / Litre (L) |
Comparison: This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period, and treatment.90% CI: [143.17, 192.53]
Primary
Maximum Measured Concentration of BI 1323495 in Plasma
Maximum measured concentration of BI 1323495 in plasma (Cmax). The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for sequence, subjects nested within sequences, period, and treatment. Confidence intervals were calculated based on the residual error from the ANOVA.
Time frame: Within 2 hours before and then 20 minutes (min), 40 min, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48, 72 and 96 hours after drug administration
Population: PK parameter analysis set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK endpoint 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) |
|---|---|---|
| BI 1323495 Fed (T) | Maximum Measured Concentration of BI 1323495 in Plasma | NA nanomol (nmol) / Litre (L) |
| BI 1323495 Fasted (R) | Maximum Measured Concentration of BI 1323495 in Plasma | NA nanomol (nmol) / Litre (L) |
Comparison: This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period, and treatment.90% CI: [179.82, 308.42]
Secondary
Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity
Area under the concentration-time curve of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for sequence, subjects nested within sequences, period, and treatment. Confidence intervals were calculated based on the residual error from the ANOVA.
Time frame: Within 2 hours before and then 20 minutes (min), 40 min, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 48, 72 and 96 hours after drug administration
Population: PK parameter analysis set (PKS): This subject set included all subjects from the TS who provided at least 1 primary or secondary PK endpoint 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) |
|---|---|---|
| BI 1323495 Fed (T) | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | NA nanomol (nmol) * hours (h) / Litre (L) |
| BI 1323495 Fasted (R) | Area Under the Concentration-time Curve of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity | NA nanomol (nmol) * hours (h) / Litre (L) |
Comparison: This model included effects accounting for the following sources of variation: sequence, subjects within sequences, period, and treatment.90% CI: [140.11, 181.34]