Healthy
Conditions
Brief summary
The primary objective of the current study is to investigate the relative bioavailability of three trial formulations of BI 207127, the trial formulation 2 (TFII), the final formulation (FF), and a FF modified formulation. All formulations are supplied as film-coated Tablets and administered as single dose treatments of BI 207127 (3 film-coated Tablets) in healthy volunteers, with the aim to compare the bioavailability of the three formulations. All treatments will be applied fed, 30 minutes after start of the intake of a standard normal breakfast.
Interventions
DRUGBI 207127
Medium dose film-coated tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males according to a complete medical history, including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests 2. Age =21and Age =50 years 3. Body mass index =18.5 and BMI = 29.9 kg/m2 4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.
Exclusion criteria
1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. Surgery of the gastrointestinal tract (except appendectomy) 5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders 6. History of relevant orthostatic hypotension, fainting spells or blackouts 7. Chronic or relevant acute infections 8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 9. Intake of drugs with a long half-life (\> 24 hours) within at least 10 half-lifes prior to administration of the trial drug or during the trial 10. Use of drugs which might reasonably influence the results of the trial within 10 days prior to administration or during the trial 11. Participation in another trial with an investigational drug within two months prior to administration of the trial drug or during the trial 12. Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day) 13. Alcohol abuse (more than 40 g/day) 14. Drug abuse 15. Blood donation (more than 100 mL within four weeks prior to first administration of the trial drug or during the trial) 16. Excessive physical activities (within one week prior to first administration of the trial drug or during the trial) 17. Any laboratory value outside the reference range that is of clinical relevance 18. Inability to comply with dietary regimen of trial site 19. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms) 20. A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) 21. History of photosensitivity or recurrent rash 22. Subject is not willing to avoid sun exposure from the first administration of the trial drug until the end of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-∞ | 1:00 (h) hour before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration | Area under the concentration-time curve of Deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Cmax | 1:00 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration | Maximum measured concentration of Deleobuvir in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Subjects This study was conducted in healthy male subjects as open-label, single-dose, randomised three-way crossover trial to investigate relative bioavailability. Each subject was planned to receive all 3 treatments in a randomly assigned order. The treatments were 3 single doses of 600 mg (3 film-coated tablets à 200 mg each) of Deleobuvir, either as TF II (trial formulation 2) formulation, FF (final formulation) formulation or as FF modified formulation. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment 1 (Single Dose) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment 3 (Single Dose) | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 16 | 4 / 17 | 3 / 18 | 7 / 18 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 | 0 / 18 | 0 / 18 |
Outcome results
Primary
AUC0-∞
Area under the concentration-time curve of Deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1:00 (h) hour before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration
Population: The pharmacokinetic set (PKS) included all subjects in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK and no vomiting must have occurred at or before two times the median tmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Deleobuvir Trial Formulation II | AUC0-∞ | 10600 nmol*h/L | Geometric Coefficient of Variation 45 |
| Deleobuvir Final Formulation | AUC0-∞ | 12400 nmol*h/L | Geometric Coefficient of Variation 57.3 |
| Deleobuvir Final Formulation Modified | AUC0-∞ | 13600 nmol*h/L | Geometric Coefficient of Variation 66 |
Comparison: Relative bioavailability comparison of Deleobuvir Trial Formulation II (reference) and Deleobuvir Final Formulation (test) in pairwise comparison. (reference : test)90% CI: [108, 141.1]
Comparison: relative bioavailability comparison of Deleobuvir Final Formulation modified (test) and Deleobuvir Final Formulation (reference) in pairwise comparison. (reference : test)90% CI: [88.6, 136.1]
Primary
Cmax
Maximum measured concentration of Deleobuvir in plasma. The measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: 1:00 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 48:00 h after drug administration
Population: The pharmacokinetic set (PKS).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Deleobuvir Trial Formulation II | Cmax | 2460 nmol/L | Geometric Coefficient of Variation 48.3 |
| Deleobuvir Final Formulation | Cmax | 2990 nmol/L | Geometric Coefficient of Variation 53.6 |
| Deleobuvir Final Formulation Modified | Cmax | 3070 nmol/L | Geometric Coefficient of Variation 73.1 |
Comparison: relative bioavailability comparison of Deleobuvir Final Formulation (test) and Deleobuvir Trial Formulation II (reference) in pairwise comparison. (test : reference)90% CI: [107.9, 139.1]
Comparison: relative bioavailability comparison of Deleobuvir Final Formulation modified (test) and Deleobuvir Final Formulation (reference) in pairwise comparison. (test : reference)90% CI: [83.1, 139.4]