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Bioequivalence of two 12.5 mg empagliflozin/500 mg metformin fixed dose combination tablets compared to the free combination of empagliflozin 25 mg and metformin 1000 mg in healthy male and female volunteers under fed conditions
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test - Empagliflozin/Metformin | Experimental | fixed dose combination of 2 tablets of 12.5 mg Empagliflozin and 500 mg Metformin, oral with 200 mL of water uder fed conditions |
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| Reference - Empagliflozin + Metformin | Experimental | free combination of 1 tablet of 25 mg Empagliflozin and 1 tablet of 1000 mg of Metformin, oral with 200 mL of water under fed conditions |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin | Drug | Test Therapy - fixed dose combination of 2 tablets of 12.5 mg Empagliflozin and 500 mg Metformin |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve of the Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
| Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve of the Metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
| Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax) | Maximum measured concentration of the Empagliflozin in plasma (Cmax). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
| Maximum Measured Concentration of the Metformin in Plasma (Cmax) | Maximum measured concentration of the Metformin in plasma (Cmax). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | Area under the concentration-time curve of the Empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity observed). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1276.27.001 Boehringer Ingelheim Investigational Site | Saint Petersburg | Russia |
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Actual number of subjects enrolled in fact represents entered / randomized subjects due to the study set up.
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| ID | Title | Description |
|---|---|---|
| FG000 | Fixed Dose Combination (FDC) / Empagliflozin + Metformin | Participants first received 2 film-coated tablets of 12.5 milligram (mg) Empagliflozin and 500 mg Metformin as a single dose in a fixed dose combination (FDC), then they received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose. The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal. Single dose in each treatment period was separated by a washout phase of at least 5 days between drug administrations. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (4 Days) |
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| Metformin | Drug | Test Therapy - fixed dose combination of 2 tablets of 12.5 mg Empagliflozin and 500 mg Metformin |
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| Empagliflozin | Drug | Reference Therapy - free combination of 1 tablets of 25 mg Empagliflozin and 1000 mg Metformin |
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| Metformin | Drug | Reference Therapy - free combination of 1 tablets of 25 mg Empagliflozin and 1000 mg Metformin |
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| PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
| PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
| Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | Area under the concentration-time curve of the Metformin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity observed). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
| FG001 | Empagliflozin + Metformin / Fixed Dose Combination (FDC) | Participants first received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose, then they received 2 film-coated tablets of 12.5 milligram (mg) Empagliflozin and 500 mg Metformin as a single dose in a fixed dose combination (FDC). The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal. Single dose in each treatment period was separated by a washout phase of at least 5 days between drug administrations. |
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| NOT COMPLETED |
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| Washout Period (5 Days) |
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| Treatment Period 2 (4 Days) |
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Treated set (TS): all subjects who were randomised to study medication and were documented to have received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Fixed Dose Combination (FDC) / Empagliflozin + Metformin | Participants first received 2 film-coated tablets of 12.5 milligram (mg) Empagliflozin and 500 mg Metformin as a single dose in a fixed dose combination (FDC), then they received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose. The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal. Single dose in each treatment period was separated by a washout phase of at least 5 days between drug administrations. |
| BG001 | Empagliflozin + Metformin / Fixed Dose Combination (FDC) | Participants first received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose, then they received 2 film-coated tablets of 12.5 milligram (mg) Empagliflozin and 500 mg Metformin as a single dose in a fixed dose combination (FDC). The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal. Single dose in each treatment period was separated by a washout phase of at least 5 days between drug administrations. |
| BG002 | 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve of the Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | Pharmacokinetic analysis set (PKS): all subjects from treated set (TS) who provided at least 1 primary or secondary Pharmacokinetic (PK) endpoint value that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation. Subject was included, even if he/she contributed only 1 PK value for one period. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomol (nmol)* hours (h) / Litre (L) | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
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| Primary | Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve of the Metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | Pharmacokinetic analysis set (PKS): all subjects from the TS who provided at least 1 primary or secondary Pharmacokinetic (PK) endpoint value that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation. Thus, subject was included, even if he/she contributed only 1 PK value for one period. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram (ng)*h /millilitre (mL) | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
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| Primary | Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax) | Maximum measured concentration of the Empagliflozin in plasma (Cmax). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | Pharmacokinetic analysis set (PKS): all subjects from the TS who provided at least 1 primary or secondary Pharmacokinetic (PK) endpoint value that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation. Thus, subject was included, even if he/she contributed only 1 PK value for one period. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
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| Primary | Maximum Measured Concentration of the Metformin in Plasma (Cmax) | Maximum measured concentration of the Metformin in plasma (Cmax). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | Pharmacokinetic analysis set (PKS): all subjects from the TS who provided at least 1 primary or secondary Pharmacokinetic (PK) endpoint value that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation. Thus, subject was included, even if he/she contributed only 1 PK value for one period. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
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| Secondary | Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | Area under the concentration-time curve of the Empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity observed). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | Pharmacokinetic analysis set (PKS): all subjects from the TS who provided at least 1 primary or secondary Pharmacokinetic (PK) endpoint value that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation. Thus, subject was included, even if he/she contributed only 1 PK value for one period. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
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| Secondary | Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC 0-infinity) | Area under the concentration-time curve of the Metformin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-infinity observed). Geometric means (gMeans) represent adjusted gMeans and geometric coefficient of variation (gCV) reflects the intra-individual gCV (%) from the mixed model analysis. | Pharmacokinetic analysis set (PKS): all subjects from the TS who provided at least 1 primary or secondary Pharmacokinetic (PK) endpoint value that was judged as PK evaluable and was not affected by protocol violations relevant to the statistical evaluation. Thus, subject was included, even if he/she contributed only 1 PK value for one period. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | PK plasma samples were taken at: 2 hours (h) before drug administration and 20 minutes, 40 minutes, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration. |
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From first drug administration until 14 days after the last drug administration, up to 27 days.
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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 | Empagliflozin / Metformin (FDC) | Participants received 2 film-coated tablets of 12.5 milligram (mg) Empagliflozin and 500 mg Metformin as a single dose in a fixed dose combination (FDC). The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal. | 0 | 24 | 0 | 24 | ||
| EG001 | Empagliflozin + Metformin Free Combination | Participants received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose. The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal. | 0 | 25 | 0 | 25 |
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Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| 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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Assessment of bioequivalence was based upon 2-sided 90% confidence intervals (CIs) for the ratio of the geometric means (gMeans) with acceptance range of 80.00 to 125.00%
Participants received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose. The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal.
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Participants received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose. The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal.
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Participants received free combination of 1 film-coated tablet of 25 mg Empagliflozin and 1 film-coated tablet of 1000 mg Metformin (brand name: Glucophage) as a single dose. The study medication was administered orally in the morning with 200 mL of water after intake of a high-fat, high-caloric meal.
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