Healthy
Conditions
Brief summary
The main objective of this trial is to investigate the relative bioavailability of BI 1323495 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
DRUGItraconazole
Oral solution
DRUGBI 1323495
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 * further inclusion criteria apply
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, blood coagulation, 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 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 * Current or history of relevant kidney, urinary tract diseases or abnormalities (e.g. nephrolithiasis, hydronephrosis, acute or chronic nephritis, renal injury, renal failure) * Estimated glomerular filtration rate according to CKD-EPI formula \< 90 mL/min at screening * 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) * History of drug induced liver injury * Liver enzymes (ALT, AST, GGT) above upper limit of normal at the screening examination * History of heart failure, or any evidence of ventricular dysfunction * Known sorbitol/polyols intolerance * Subjects with female partner of childbearing potential who are unwilling to use male contraception (condom or sexual abstinence) from first administration until 30 days after last administration of trial medication
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 (AUC0-tz) | Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after 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) |
| Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration. | Maximum measured concentration of BI 1323495 in plasma (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Cure of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration. | Area under the concentration-time cure of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) |
Countries
Germany
Participant flow
Recruitment details
This is an open-label, two-treatment, two-period, one-way fixed-sequence design to investigate the relative bioavailability of a single oral dose of BI 1323495 when given alone (Period 1) as reference treatment (R) or in combination with itraconazole (Period 2) as test treatment (T) in healthy male subjects.
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 1323495 (R) / BI 1323495 + Itraconazole (T) A single oral dose of 10 milligrams (mg) BI 1323495, film-coated tablet, was administered once on day 1, period 1, visit 2, as reference treatment R, followed by a washout period of at least 7 days, followed by period 2, visit 3, in which a single oral dose of 200 mg itraconazole (oral solution, 20 milliliter (mL) per day with 10 mg/mL) was administered once daily from day -3 to day 7, in total 10 doses. On day 1 of visit 3, 4th day of itraconazole treatment, a single oral dose of 10 mg BI 132345 was administered 1 hour (h) after itraconazole administration as test treatment T.
BI 1323495 and itraconazole were orally administered with 240 mL of water after an overnight fast of at least 10 h for BI 1323495 and 9 h for itraconazole. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | BI 1323495 (R) / BI 1323495 + Itraconazole (T) |
|---|---|
| Age, Continuous | 38.9 Years STANDARD_DEVIATION 7.8 |
| 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 | 2 / 14 | 2 / 14 | 5 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 |
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 (AUC0-tz)
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)
Time frame: Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration.
Population: Pharmacokintetic parameter analysis set (PKS): Participants in the treated set (TS) with at least 1 primary or secondary pharmacokinetic (PK) endpoint who were not excluded due to a protocol deviation relevant to the evaluation of PK or PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1323495 (R) | 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) | 124.15 Nanomoles * hour per Liter |
| BI 1323495 + Itraconazole (T) | 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) | 215.66 Nanomoles * hour per Liter |
90% CI: [154.58, 195.21]ANOVA
Primary
Maximum Measured Concentration of BI 1323495 in Plasma (Cmax)
Maximum measured concentration of BI 1323495 in plasma (Cmax)
Time frame: Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration.
Population: Pharmacokintetic parameter analysis set (PKS): Participants in the treated set (TS) with at least 1 primary or secondary pharmacokinetic (PK) endpoint who were not excluded due to a protocol deviation relevant to the evaluation of PK or PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1323495 (R) | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 10.49 Nanomoles per Liter |
| BI 1323495 + Itraconazole (T) | Maximum Measured Concentration of BI 1323495 in Plasma (Cmax) | 14.41 Nanomoles per Liter |
90% CI: [120.84, 156.24]ANOVA
Secondary
Area Under the Concentration-time Cure of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Area under the concentration-time cure of BI 1323495 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
Time frame: Within 3 hours (h) prior and 0.33, 0.67, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 34, 47, 71, 95 (period 1) and additional 119, 143, 167h (period 2) after administration.
Population: Pharmacokintetic parameter analysis set (PKS): Participants in the treated set (TS) with at least 1 primary or secondary pharmacokinetic (PK) endpoint who were not excluded due to a protocol deviation relevant to the evaluation of PK or PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1323495 (R) | Area Under the Concentration-time Cure of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 178.29 Nanomoles * hour per Liter |
| BI 1323495 + Itraconazole (T) | Area Under the Concentration-time Cure of BI 1323495 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 300.66 Nanomoles * hour per Liter |
90% CI: [145.59, 195.34]ANOVA