Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the effect of multiple doses of itraconazole on the pharmacokinetics of BI 1026706 given as single dose. The assessment of safety and tolerability of BI 1026706 is an additional objective of this trial. Furthermore, the pharmacokinetics of the metabolite BI 1072668 will be explored.
Interventions
DRUGBI 1026706
Single dose of BI 1026706 on Day 1
DRUGItraconazole
7 days of itraconazole treatment combined with a single dose of BI 1026706 on the fourth day
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 investigators assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests * Age of 18 to 55 years (incl.) * 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 GCP and local legislation
Exclusion criteria
* Any finding in the medical examination (including BP, PR or 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 50 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 judged as clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * 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 (such as epilepsy), 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) * Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication * Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval * Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day) * Inability to refrain from smoking during in-house confinement at trial site * 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 * 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 Torsades 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 considered not able to understand and comply with study requirements, or because he 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 Curve of BI 1026706 From 0 to the Last Quantifiable Data Point (AUC0-tz) | -3 hours (h) before drug administration and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration | Area under the concentration-time curve of BI 1026706 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) |
| Maximum Concentration of BI 1026706 (Cmax) | 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration | Maximum measured concentration of BI 1026706 in plasma (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of BI 1026706 From 0 Extrapolated to Infinity (AUC0-inf) | -3 hours (h) before drug administration and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration | Area under the concentration-time curve of BI 1026706 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) |
Countries
Germany
Participant flow
Pre-assignment details
An open-label, randomised, two-period, two-sequence crossover study with healthy male subjects
Participants by arm
| Arm | Count |
|---|---|
| Sequence RT Treatment R (BI 1026706 alone):
Oral administration of a single dose of 25 mg BI 1026706 film-coated tablets was given on Day 1.
Treatment T (itraconazole + BI 1026706):
Itraconazole (200 mg) as capsules was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).
The single dose administrations of BI 1026706 in treatments R and T were separated by a wash-out period of at least 10 days. | 8 |
| Sequence TR Treatment T (itraconazole + BI 1026706):
Itraconazole (200 mg) as capsules was given orally twice daily as a loading dose on Day -3 and once daily from Day -2 to Day 4 (7 days in total). A single dose of 25 mg BI 1026706 was given orally on the fourth day (Day 1) of the itraconazole treatment (1 h after the itraconazole administration on the respective day).
Treatment R (BI 1026706 alone):
Oral administration of a single dose of 25 mg BI 1026706 film-coated tablets was given on Day 1.
The single dose administrations of BI 1026706 in treatments T and R were separated by a wash-out period of at least 10 days. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Sequence RT | Sequence TR | Total |
|---|---|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 10.2 | 33.0 years STANDARD_DEVIATION 8.1 | 35.4 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 16 | 4 / 16 | 5 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Area Under the Curve of BI 1026706 From 0 to the Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of BI 1026706 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)
Time frame: -3 hours (h) before drug administration and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration
Population: Pharmacokinetic set (PKS) included all treated subjects that provided at least 1 primary or secondary pharmacokinetic parameter that was not excluded due to a protocol violation relevant to the evaluation of pharmacokinetics or due to pharmacokinetic non-evaluability..
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment R (BI 1026706 Alone) | Area Under the Curve of BI 1026706 From 0 to the Last Quantifiable Data Point (AUC0-tz) | 921 nmol*h/L | Geometric Coefficient of Variation 47.8 |
| Treatment T (Itraconazole + BI 1026706) | Area Under the Curve of BI 1026706 From 0 to the Last Quantifiable Data Point (AUC0-tz) | 1580 nmol*h/L | Geometric Coefficient of Variation 55.9 |
90% CI: [160.5, 193.2]ANOVA
Primary
Maximum Concentration of BI 1026706 (Cmax)
Maximum measured concentration of BI 1026706 in plasma (Cmax)
Time frame: 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment R (BI 1026706 Alone) | Maximum Concentration of BI 1026706 (Cmax) | 206 nmol/L | Geometric Coefficient of Variation 48.9 |
| Treatment T (Itraconazole + BI 1026706) | Maximum Concentration of BI 1026706 (Cmax) | 279 nmol/L | Geometric Coefficient of Variation 62.2 |
90% CI: [109.9, 169.4]ANOVA
Secondary
Area Under the Curve of BI 1026706 From 0 Extrapolated to Infinity (AUC0-inf)
Area under the concentration-time curve of BI 1026706 in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Time frame: -3 hours (h) before drug administration and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 47h, 71h and 95h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment R (BI 1026706 Alone) | Area Under the Curve of BI 1026706 From 0 Extrapolated to Infinity (AUC0-inf) | 943 nmol*h/L | Geometric Coefficient of Variation 46.9 |
| Treatment T (Itraconazole + BI 1026706) | Area Under the Curve of BI 1026706 From 0 Extrapolated to Infinity (AUC0-inf) | 1600 nmol*h/L | Geometric Coefficient of Variation 54.6 |
90% CI: [159.1, 192]ANOVA