Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the relative bioavailability of BI 730357 in plasma when given as oral single dose together with multiple oral doses of itraconazole (Test, T) as compared to when given alone as oral single dose (Reference, R)
Interventions
DRUGBI 730357
0 mg BI 730357 tablet orally on Day 1
DRUGItraconazole
20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.
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)) 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 (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 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 Electrocardiogram (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 In addition, the following trial-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2. | AUC0-tz, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 to the last quantifiable data point is presented. |
| Maximum Measured Concentration of the BI 730357 in Plasma (Cmax) | Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2. | Cmax, maximum measured concentration of the BI 730357 in plasma is presented here. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2. | AUC0-∞, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 extrapolated to infinity is presented here. |
Countries
Germany
Participant flow
Recruitment details
This was an open-label, two-treatment, two-period, one-way crossover trial in healthy participants in order to compare the test treatment (T) to the reference treatment (R). All participants underwent treatment R in Period 1 (Visit 2) and treatment T in Period 2 (Visit 3). There was at least 10 days washout between the administrations of BI 730357.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist site which would then ensured that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| BI 730357 Alone/ BI 730357+Itraconazole Participants were administered 50 milligram (mg) BI 730357 tablet orally on Day 1 alone in treatment period 1 (R) and along with 20 milliliter (mL) of 10 mg/ mL Itraconazole oral solution on Day 1 of treatment period 2 (T). Itraconazole was administered once daily on Day -3, -2, -1 and 1 before administration of BI 730357 and on Day 2 to 9 in treatment period 2 only. There was a washout interval of at least 10 days between the administrations of BI 730357. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | BI 730357 Alone/ BI 730357+Itraconazole |
|---|---|
| Age, Continuous | 37.8 Years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| 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 | 14 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 1 / 14 | 5 / 14 | 8 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Area Under the Concentration-time Curve of the BI 730357 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 the BI 730357 in plasma over the time interval from 0 to the last quantifiable data point is presented.
Time frame: Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.
Population: Pharmacokinetic (PK) parameter set (PKS): The PKS included all subjects of the TS who provided at least 1 primary or secondary PK parameter that was not excluded due to relevant protocol deviations or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 730357 + Itraconazole (T) | Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 43239.08 Nanomole* hour/ Litre (nmol*h/ L) |
| BI 730357 (R) | Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | 6657.49 Nanomole* hour/ Litre (nmol*h/ L) |
Comparison: Statistical model was an analysis of variance (ANOVA) on the logarithmic scale including 'subjects' as random effect and 'treatment' as fixed effect.90% CI: [541.29, 779.29]
Primary
Maximum Measured Concentration of the BI 730357 in Plasma (Cmax)
Cmax, maximum measured concentration of the BI 730357 in plasma is presented here.
Time frame: Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 730357 + Itraconazole (T) | Maximum Measured Concentration of the BI 730357 in Plasma (Cmax) | 311.01 nmol/ L |
| BI 730357 (R) | Maximum Measured Concentration of the BI 730357 in Plasma (Cmax) | 186.36 nmol/ L |
Comparison: Statistical model was an analysis of variance (ANOVA) on the logarithmic scale including 'subjects' as random effect and 'treatment' as fixed effect.90% CI: [148.42, 187.64]
Secondary
Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
AUC0-∞, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 extrapolated to infinity is presented here.
Time frame: Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BI 730357 + Itraconazole (T) | Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 64934.55 nmol*h/ L |
| BI 730357 (R) | Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 6971.67 nmol*h/ L |
Comparison: Statistical model was an analysis of variance (ANOVA) on the logarithmic scale including 'subjects' as random effect and 'treatment' as fixed effect.90% CI: [785.19, 1104.85]