Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the relative bioavailability of BI 409306 tablets with prior 7-day intake of rifampicin tablets (Test, T) compared to BI 409306 tablets without prior administration of rifampicin (Reference, R) following oral administration in healthy male subjects. The secondary objective is the evaluation and comparison of several pharmacokinetic parameters between the treatments. The secondary objectives will be assessed by descriptive statistics.
Interventions
DRUGBI 409306
Reference and Test Treatment
DRUGRifampicin
Test Treatment
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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.) * 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 45 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 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 * Current smoker or ex-smoker who quit smoking less than 30 days prior to screening. * 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 * 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 |
|---|---|---|
| Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration. | Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. |
| Maximum Measured Concentration of BI 409306 in Plasma (Cmax) | Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration. | Maximum measured concentration of BI 409306 in plasma (Cmax) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration. | Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. |
Countries
Germany
Participant flow
Recruitment details
This study was an open-label, mono-center clinical trial in healthy male subjects applied a two-period, two-treatment, fixed sequence design. Each subject participated in the two trial periods (Visit 2 \[Days 1 and 2\] and Visit 3 \[Days -7 to 2\] and received the two treatments in the same sequence in Period 1 the Reference treatment (R) and afterwards in Period 2 the Test treatment (T).
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended one specialist site which would then ensure that they (the subjects) met all inclusion/exclusion criteria. The subjects were not included into the trial if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| BI 409306 (R), Then BI 409306 After Pretreatment With Rifampicin (T) Subjects were administered during Period 1 on Day 1/Visit 2 a single dose of 50 milligrams (mg) of BI 409306 film-coated tablet orally with 240 millilitre (mL) of water (reference treatment, R).
On Days -7 to -1 /Visit 3 of Period 2 participants were administered rifampicin 600 mg Eremfat® film-coated tablet orally with 240 mL of water once per day during the evenings. Afterwards on Day 1/Visit 3, participants were administered a single dose of 50 mg BI 409306 orally approximately 14 hours after the last rifampicin dose (test treatment, T).
Due to the short half-life of BI 409306, trial period 2 directly followed trial period 1 without a wash-out period. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | BI 409306 (R), Then BI 409306 After Pretreatment With Rifampicin (T) |
|---|---|
| Age, Continuous | 38.7 years STANDARD_DEVIATION 9.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 15 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 1 / 15 | 15 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported.
Time frame: Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): all subjects in the TS who provided at least one primary or secondary PK parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| T: BI 409306 + Rifampicin Pretreatment | Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | NA nanomole*hour/liter (nmol·h/L) |
| R: BI 409306 | Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | NA nanomole*hour/liter (nmol·h/L) |
Comparison: The main focus is on estimation, therefore no hypothesis was tested. The statistical analysis model for the primary endpoints is an ANOVA (analysis of variance). This model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subjects' will be considered as random, whereas the treatment effect will be considered as fixed. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.90% CI: [5.74, 10.601]
Primary
Maximum Measured Concentration of BI 409306 in Plasma (Cmax)
Maximum measured concentration of BI 409306 in plasma (Cmax) is reported.
Time frame: Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): all subjects in the TS who provided at least one primary or secondary PK parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| T: BI 409306 + Rifampicin Pretreatment | Maximum Measured Concentration of BI 409306 in Plasma (Cmax) | NA nanomole/liter (nmol/L) |
| R: BI 409306 | Maximum Measured Concentration of BI 409306 in Plasma (Cmax) | NA nanomole/liter (nmol/L) |
Comparison: The main focus is on estimation, therefore no hypothesis was tested. The statistical analysis model for the primary endpoints is an ANOVA (analysis of variance). This model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subjects' will be considered as random, whereas the treatment effect will be considered as fixed. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.90% CI: [6.767, 14.098]
Secondary
Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time curve of BI 409306 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported.
Time frame: Within 3 hours (h) before and 0.333h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 11h, 12h, 24h after drug administration.
Population: Pharmacokinetic (PK) parameter analysis set (PKS): all subjects in the TS who provided at least one primary or secondary PK parameter not flagged for exclusion due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| T: BI 409306 + Rifampicin Pretreatment | Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA nanomole*hour/liter (nmol·h/L) |
| R: BI 409306 | Area Under the Concentration-time Curve of BI 409306 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | NA nanomole*hour/liter (nmol·h/L) |
Comparison: Since the main focus is on estimation and not testing, therefore no hypothesis was tested.The statistical analysis model is an ANOVA (analysis of variance) model on the logarithmic scale. This model included effects accounting for the following sources of variation: 'subjects' and 'treatment'. The effect 'subjects' will be considered as random, whereas the treatment effect will be considered as fixed. The PK endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model.90% CI: [6.081, 11.126]