Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the effect of rifampicin on the pharmacokinetics of BI 894416.
Interventions
DRUGBI 894416
tablet
DRUGRifampicin
tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 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 50 years (inclusive) * Body mass index (BMI) of 18.5 to 29.9 kg/m2 (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) and including the neurological examination) 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 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 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 * Smoker (unless the subject quit smoking for at least 3 months prior to first planned administration of trial medication) * Alcohol abuse (consumption of more than 24 g per day) * Drug abuse or positive drug screening * Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial * Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial * Inability to comply with the dietary regimen of the 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 Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome) * Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study * History of relevant neurological disorder affecting the peripheral or central nervous system (this includes, but is not limited to: stroke, epilepsy, inflammatory or atrophic diseases affecting the nervous system, cluster headache or any cancer of the nervous system). Febrile seizures in childhood or adolescence, recovered carpal tunnel syndrome, recovered uncomplicated meningitis, recovered herpes zoster, tension headache, occasional benign tics (e.g. due to stress) or minor par- or dysesthesia (e.g. as a side effect of prior blood withdrawal) do not constitute a history of relevant neurological disorder. * History of immunological disease except allergy not relevant to the trial (such as mild hay fever or dust mite allergy) and except asthma in childhood or adolescence * History of cancer (other than successfully treated basal cell carcinoma) * Liver enzymes (ALT, AST, gGT, AP) above upper limit of normal at the screening examination * Within 10 days prior to administration of trial medication, use of any drug that could reasonably inhibit platelet aggregation or coagulation (e.g., acetylsalicylic acid) * Male subjects with Woman of child bearing potential (WOCBP) partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of first administration of trial medication until 30 days after the last administration of trial medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours before administration of BI 894416 and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34 and 48 hours after administration of BI 894416. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). |
| Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | Within 3 hours before administration of BI 894416 and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34 and 48 hours after administration of BI 894416. | Maximum measured concentration of BI 894416 in plasma (Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours before administration of BI 894416 and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34 and 48 hours after administration of BI 894416. | Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). |
Countries
Germany
Participant flow
Recruitment details
Open-label, 2-treatment, 2-period, 1-way crossover trial to compare the test treatment (T) to the reference treatment (R). The treatments were 1 single dose of BI 894416 following 7 days of pretreatment with rifampicin (T) and 1 single dose of BI 894416 given alone (R) with a washout period of at least 10 days between administrations of BI 894416.
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 |
|---|---|
| BI 894416 Alone (Reference)/BI 894416 + Rifampicin (Test) In treatment period 1, Day 1, participants were administered one oral single dose of 50 milligram (mg) BI 894416 as tablet formulation (2 tablets of 25 mg administered in the fasting state with 240 milliliter (mL) of water) (reference treatment in period 1, Reference). In treatment period 2, from Day -7 to Day -1, participants were administered one film-coated tablet of 600 mg rifampicin with 240 mL of water once daily, followed by one oral single dose of 50 mg BI 894416 as tablet formulation (2 tablets of 25 mg administered in the fasting state with 240 mL of water) on Day 1 (test treatment in period 2, Test). There was a washout period of at least 10 days between the administrations of BI 894416. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | BI 894416 Alone (Reference)/BI 894416 + Rifampicin (Test) |
|---|---|
| Age, Continuous | 37.3 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 14 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 2 / 16 | 16 / 16 | 4 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Time frame: Within 3 hours before administration of BI 894416 and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34 and 48 hours after administration of BI 894416.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) included all participants who were treated with at least 1 dose of trial drug and provided at least 1 PK endpoint defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 894416 Alone (Reference, R) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 9077.08 hour * nanomole / liter |
| BI 894416 + Rifampicin (Test, T) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 951.58 hour * nanomole / liter |
Comparison: Relative bioavailability90% CI: [9.74, 11.28]Mixed Models Analysis
Primary
Maximum Measured Concentration of BI 894416 in Plasma (Cmax)
Maximum measured concentration of BI 894416 in plasma (Cmax).
Time frame: Within 3 hours before administration of BI 894416 and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34 and 48 hours after administration of BI 894416.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) included all participants who were treated with at least 1 dose of trial drug and provided at least 1 PK endpoint defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 894416 Alone (Reference, R) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | 1624.79 nanomole / liter |
| BI 894416 + Rifampicin (Test, T) | Maximum Measured Concentration of BI 894416 in Plasma (Cmax) | 487.98 nanomole / liter |
Comparison: Relative bioavailability90% CI: [25.76, 35.02]Mixed Models Analysis
Secondary
Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 894416 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Time frame: Within 3 hours before administration of BI 894416 and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34 and 48 hours after administration of BI 894416.
Population: Pharmacokinetic (PK) parameter analysis set (PKS) included all participants who were treated with at least 1 dose of trial drug and provided at least 1 PK endpoint defined as primary or secondary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 894416 Alone (Reference, R) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 9047.51 hour * nanomole / liter |
| BI 894416 + Rifampicin (Test, T) | Area Under the Concentration-time Curve of BI 894416 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 939.98 hour * nanomole / liter |
Comparison: Relative bioavailability90% CI: [9.66, 11.18]Mixed Models Analysis