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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000082-20 | EudraCT Number | EudraCT |
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The primary objective of this trial is to establish bioequivalence of two fixed dose combination (FDC) tablets (containing medium dose empagliflozin/500 mg metformin [Test 1] and low dose empagliflozin/500 mg metformin [Test 2]) and of the single tablets (medium dose empagliflozin tablets + Glucophage® 500 mg tablet [Reference 1] and low dose empagliflozin tablet + Glucophage® 500 mg tablet [Reference 2]) when administered together after a high fat, high caloric meal.
The assessment of safety and tolerability will be an additional objective of this trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FDC empagliflozin dose 1 and metformin | Experimental | fix dose combination tablet after intake of a high fat, high caloric meal |
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| empagliflozin dose 1 + metformin tablets | Active Comparator | single tablets after intake of a high fat, high caloric meal |
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| FDC empagliflozin dose 2 and metformin | Experimental | fix dose combination tablet after intake of a high fat, high caloric meal |
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| empagliflozin dose 2 + metformin tablets | Active Comparator | single tablets after intake of a high fat, high caloric meal |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| empagliflozin | Drug | single tablet empagliflozin |
| |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-∞ for Empagliflozin | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Empagliflozin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
| AUC0-∞ for Metformin | AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
| Cmax for Empagliflozin | Cmax (maximum measured concentration of the analyte in plasma) for Empagliflozin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
| Cmax for Metformin | Cmax (maximum measured concentration of the analyte in plasma) for Metformin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-tz for Empagliflozin | AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) for Empagliflozin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
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Inclusion criteria:
Exclusion criteria:
1. Any relevant deviation from healthy conditions
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1276.6.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
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| ID | Title | Description |
|---|---|---|
| FG000 | FDC Empa12.5/ Empa12.5+Met500/ FDC Empa5/ Empa5+Met500 | Participants first received Treatment T1 (12.5 mg empagliflozin/500 mg metformin Fixed Dose Combination (FDC)). After a washout phase of at least 5 days, they then received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets). Oral administration. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| metformin (Glucophage®) |
| Drug |
single tablet metformin |
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| metformin (Glucophage®) | Drug | single tablet metformin |
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| empagliflozin | Drug | single tablet empagliflozin |
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| empagliflozin and metformin | Drug | FDC tablet empagliflozin and metformin |
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| empagliflozin and metformin | Drug | FDC tablet empagliflozin and metformin |
|
| AUC0-tz for Metformin |
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) for Metformin |
| 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
| FG001 | Empa12.5+Met500/ FDC Empa12.5/ Empa5+Met500/ FDC Empa5 | Participants first received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T1 (12.5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). Oral administration. |
| FG002 | FDC Empa5/ Empa5+Met500/ FDC Empa12.5/ Empa12.5+Met500 | Participants first received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets)Treatment T1 (12.5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). Oral administration. |
| FG003 | Empa5+Met500/ FDC Empa5/ Empa12.5+Met500/ FDC Empa12.5 | Participants first received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T1 (12.5 mg empagliflozin/500 mg metformin FDC). Oral administration. |
| COMPLETED |
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| NOT COMPLETED |
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Treated set, included all subjects that entered the study and had taken at least 1 dose of trial medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | FDC Empa12.5/ Empa12.5+Met500/ FDC Empa5/ Empa5+Met500 | Participants first received Treatment T1 (12.5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets). Oral administration. |
| BG001 | Empa12.5+Met500/ FDC Empa12.5/ Empa5+Met500/ FDC Empa5 | Participants first received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T1 (12.5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). Oral administration. |
| BG002 | FDC Empa5/ Empa5+Met500/ FDC Empa12.5/ Empa12.5+Met500 | Participants first received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets)Treatment T1 (12.5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). Oral administration. |
| BG003 | Empa5+Met500/ FDC Empa5/ Empa12.5+Met500/ FDC Empa12.5 | Participants first received Treatment R2 (5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T2 (5 mg empagliflozin/500 mg metformin FDC). After a washout phase of at least 5 days, they then received Treatment R1 (12.5 mg empagliflozin and 500 mg metformin, single tablets). After a washout phase of at least 5 days, they then received Treatment T1 (12.5 mg empagliflozin/500 mg metformin FDC). Oral administration. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | AUC0-∞ for Empagliflozin | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Empagliflozin | Pharmacokinetics set (PKS) included all treated subjects with at least 1 evaluable observation for at least 1 primary pharmacokinetic endpoint without important protocol violations relevant to the statistical evaluation of pharmacokinetics who had not taken any restricted medication and had not experienced emesis before or at 2 times median tmax | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
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| Primary | AUC0-∞ for Metformin | AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin | Pharmacokinetics set (PKS) included all treated subjects with at least 1 evaluable observation for at least 1 primary pharmacokinetic endpoint without important protocol violations relevant to the statistical evaluation of pharmacokinetics who had not taken any restricted medication and had not experienced emesis before or at 2 times median tmax | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
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| Secondary | AUC0-tz for Empagliflozin | AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) for Empagliflozin | Pharmacokinetics set (PKS) included all treated subjects with at least 1 evaluable observation for at least 1 primary pharmacokinetic endpoint without important protocol violations relevant to the statistical evaluation of pharmacokinetics who had not taken any restricted medication and had not experienced emesis before or at 2 times median tmax | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
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| Primary | Cmax for Empagliflozin | Cmax (maximum measured concentration of the analyte in plasma) for Empagliflozin | Pharmacokinetics set (PKS) included all treated subjects with at least 1 evaluable observation for at least 1 primary pharmacokinetic endpoint without important protocol violations relevant to the statistical evaluation of pharmacokinetics who had not taken any restricted medication and had not experienced emesis before or at 2 times median tmax | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
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| Primary | Cmax for Metformin | Cmax (maximum measured concentration of the analyte in plasma) for Metformin | Pharmacokinetics set (PKS) included all treated subjects with at least 1 evaluable observation for at least 1 primary pharmacokinetic endpoint without important protocol violations relevant to the statistical evaluation of pharmacokinetics who had not taken any restricted medication and had not experienced emesis before or at 2 times median tmax | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
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| Secondary | AUC0-tz for Metformin | AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) for Metformin | Pharmacokinetics set (PKS) included all treated subjects with at least 1 evaluable observation for at least 1 primary pharmacokinetic endpoint without important protocol violations relevant to the statistical evaluation of pharmacokinetics who had not taken any restricted medication and had not experienced emesis before or at 2 times median tmax | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |
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From study drug administration of 1 treatment period until study drug administration in the next treatment period or date of trial completion plus 1 day, up to 8 days (and up to 16 days for one subject only)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 12.5 mg Empagliflozin and 500 mg Metformin as FDC | 12.5 mg empagliflozin/500 mg metformin as Fixed Dose Combination, oral administration | 0 | 21 | 3 | 21 | ||
| EG001 | 12.5 mg Empagliflozin and 500 mg Metformin as Single Tablets | 12.5 mg empagliflozin and 500 mg metformin as single tablets, oral administration | 0 | 23 | 6 | 23 | ||
| EG002 | 5 mg Empagliflozin and 500 mg Metformin as FDC | 5 mg empagliflozin/500 mg metformin as Fixed Dose Combination, oral administration | 0 | 23 | 3 | 23 | ||
| EG003 | 5 mg Empagliflozin and 500 mg Metformin as Single Tablets | 5 mg empagliflozin and 500 mg metformin as single tablets, oral administration | 0 | 20 | 2 | 20 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| C570240 | empagliflozin |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Male |
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| Superiority or Other |
| Adjusted by-treatment geometric means and relative bioavailability - analysis with fixed effects for all terms comparison FDC Empa12.5 : Empa12.5 + Met500, PK set AUCinfpred [nmol*h/L] for EMPAGLIFLOZIN (PLASMA EDTA). The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. | ANOVA | <.0001 | Model included effects:sequence;subjects within sequences;period and treatment with all effects as fixed. | Adjusted gMean ratio FDC/single tablets | 98.00 | Standard Error of the Mean | 8.3 | 2-Sided | 90 | 93.57 | 102.65 | *Results reported as Standard Error of the mean are Intra-individual geometric coefficient of variation [%]. | No | Superiority or Other |
| Adjusted by-treatment geometric means and relative bioavailability comparison FDC Empa5 : Empa5 + Met500 , PK set AUCinfpred [nmol*h/L] for EMPAGLIFLOZIN (PLASMA EDTA). The statistical model used was an analysis of variance (ANOVA) model on the logarithmic scale. | ANOVA | 0.0000 | Model included effects:sequence;subjects within sequences;period and treatment with subjects within sequences as random effect. | Adjusted gMean ratio FDC/single tablets | 102.79 | Standard Error of the Mean | 6.7 | 2-Sided | 90 | 99.077 | 106.633 | *Results reported as Standard Error of the mean are Intra-individual geometric coefficient of variation [%]. | No | Superiority or Other |
| Adjusted by-treatment geometric means and relative bioavailability - analysis with fixed effects for all terms comparison FDC Empa5 (T2) : Empa5 + Met500 (R2), PK set AUCinfpred [nmol*h/L] for EMPAGLIFLOZIN (PLASMA EDTA) | ANOVA | <.0001 | Adjusted gMean ratio FDC/single tablets | 102.50 | Standard Error of the Mean | 6.7 | 2-Sided | 90 | 98.78 | 106.36 | *Results reported as Standard Error of the mean are Intra-individual geometric coefficient of variation [%]. | No | Superiority or Other |
| OG003 | 5 mg Empagliflozin and 500 mg Metformin as Single Tablets | 5 mg empagliflozin and 500 mg metformin as single tablets, oral administration |
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| OG003 | 5 mg Empagliflozin and 500 mg Metformin as Single Tablets | 5 mg empagliflozin and 500 mg metformin as single tablets, oral administration |
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| OG003 |
| 5 mg Empagliflozin and 500 mg Metformin as Single Tablets |
5 mg empagliflozin and 500 mg metformin as single tablets, oral administration |
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| OG003 |
| 5 mg Empagliflozin and 500 mg Metformin as Single Tablets |
5 mg empagliflozin and 500 mg metformin as single tablets, oral administration |
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| OG003 | 5 mg Empagliflozin and 500 mg Metformin as Single Tablets | 5 mg empagliflozin and 500 mg metformin as single tablets, oral administration |
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