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Study to investigate the relative bioavailability of 5 new 400 mg tablet formulations (trial formulation II prototypes) of BI 207127 compared to the current 200 mg BI 207127 tablet formulation (trial formulation I) in healthy male volunteers with the aim to identify the best formulation for further drug development (formulation finding part / trial part 1) and to investigate the effect of food on the relative bioavailability of the most promising one of these trial formulation II prototypes (food-effect part / trial part 2).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 207127 NA (TF-I) | Active Comparator | trial part 1: 800 mg BI 207127 NA Trial formulation I (TF-I) |
|
| BI 207127 NA (TF-II) | Experimental | trial part 1: 800 mg BI 207127 NA Trial formulation II (TF-II) |
|
| BI 207127 NA delayed release | Experimental | trial part 1: 800 mg BI 207127 NA TF-II, delayed release |
|
| BI 207127 NA extended release (10% HPMC) | Experimental | trial part 1: 800 mg BI 207127 NA TF-II, extended release (10% Hydroxypropyl methyl cellulose (HPMC)) |
|
| BI 207127 NA extended release (15% PEO) | Experimental | trial part 1: 800 mg BI 207127 NA TF-II, extended release (15% Polyethylene oxide (PEO)) |
|
| BI 207127 NA extended release (20% HPMC) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 207127 NA (TF-I) | Drug | 200 mg tablet |
| |
| BI 207127 NA (TF-II) |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for BI 207127 | up to 48 hours after drug administration | |
| Cmax (maximum measured concentration of the analyte in plasma) for BI 207127 | up to 48 hours after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval from t1 to t2) | up to 24 hours after drug administration | |
| tmax (time from dosing to the maximum concentration of the analyte in plasma) | up to 48 hours after drug administration |
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Inclusion Criteria:
Exclusion Criteria:
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trial part 1: 800 mg BI 207127 NA TF-II, extended release (20% HPMC) |
|
| BI 207127 (TF-II), fed | Experimental | trial part 2 |
|
| BI 207127 (TF-II), fasted | Experimental | trial part 2 |
|
| Drug |
400 mg tablet |
|
| BI 207127 NA delayed release | Drug | 400 mg tablet |
|
| BI 207127 NA extended release (10% HPMC) | Drug | 400 mg tablet |
|
| BI 207127 NA extended release (15% PEO) | Drug | 400 mg tablet |
|
| BI 207127 NA extended release (20% HPMC) | Drug | 400 mg tablet |
|
| λz (terminal rate constant in plasma) | up to 48 hours after drug administration |
| t1/2 (terminal half-life of the analyte in plasma) | up to 48 hours after drug administration |
| MRTpo (mean residence time of the analyte in the body after p.o. administration) | up to 48 hours after drug administration |
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) | up to 48 hours after drug administration |
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) | up to 48 hours after drug administration |
| The fluctuation parameter Cmax/C12 for the ER (Extended release) formulations only | up to 48 hours after drug administration |
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) | up to 24 hours after drug administration in the food-effect part |
| fet1-t2 (fraction of analyte eliminated in urine compared to oral dose administered from time point t1 to time point t2) | up to 24 hours after drug administration in the food-effect part |
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) | up to 24 hours after drug administration in the food-effect part |
| RCmax,Met (the ratio of Cmax of the metabolite, CD 6168 to Cmax of the parent compound, BI207127) | up to 48 hours after drug administration |
| RAUC0-∞,Met (the ratio of AUC0-∞ of the metabolite, CD 6168 to AUC0-∞ of the parent compound, BI207127) | up to 48 hours after drug administration |
| AUC0-∞ for CD 6168 | up to 48 hours after drug administration |
| Cmax for CD 6168 | up to 48 hours after drug administration |
| Measurement of protein binding in human plasma for BI 207127 | up to 48 hours after drug administration in the food-effect part |
| Number of patients with adverse events | up to 9 weeks |
| Assessment of tolerability on a 4-point scale | 48 h after each drug administration |