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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-002277-65 | EudraCT Number | EudraCT |
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The primary objective of this trial is to establish bioequivalence of two FDC tablets and the single tablets when administered together after a high fat high caloric meal.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Test 1 | Experimental | fixed dose combination tablet |
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| Reference 1 | Active Comparator | empagliflozin tablets and metformin tablet |
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| Test 2 | Experimental | fixed dose combination tablet |
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| Reference 2 | Active Comparator | empagliflozin tablet and metformin tablet |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin | Drug | empagliflozin tablets and metformin tablet |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
| Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
| Empa: Maximum Measured Concentration (Cmax) | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
| Metformin: Maximum Measured Concentration (Cmax) | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (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. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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Inclusion criteria:
1. Healthy male and female subjects
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 |
|---|---|---|---|---|---|---|
| 1276.7.1 Boehringer Ingelheim Investigational Site | Biberach | Germany |
This was an open-label, randomized, 4-way crossover trial. 36 patients were randomised to one of 4 treatment sequences and treated. Each treatment period consisted of a single dose of medication followed by 72 hours of pharmacokinetic sampling, with a washout of at least 7 days between treatment periods.
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| ID | Title | Description |
|---|---|---|
| FG000 | T1 / R1 / T2 / R2 | Patients received the 4 treatments in the following order:
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| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 (3 Days) |
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| Empagliflozin + Metformin |
| Drug |
fixed dose combination tablet (low) |
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| Metformin | Drug | empagliflozin tablets and metformin tablet |
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| Metformin | Drug | empagliflozin tablet and metformin tablet |
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| Empagliflozin + Metformin | Drug | fixed dose combination tablet (low) |
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| Empagliflozin | Drug | empagliflozin tablet and metformin tablet |
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| Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (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. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
| FG001 | R1 / T1 / R2 / T2 | Patients received the 4 treatments in the following order:
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| FG002 | T2 / R2 / T1 / R1 | Patients received the 4 treatments in the following order:
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| FG003 | R2 / T2 / R1 / T1 | Patients received the 4 treatments in the following order:
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| COMPLETED |
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| NOT COMPLETED |
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| Washout Period 1 (7 Days) |
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| Treatment Period 2 (3 Days) |
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| Washout Period 2 (7 Days) |
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| Treatment Period 3 (3 Days) |
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| Washout Period 3 (7 Days) |
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| Treatment Period 4 (3 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | Total number of patients randomised and treated in the study. This was an open-label, randomized, 4-way crossover trial. 36 patients were randomised to one of 4 treatment sequences and treated. Each treatment period consisted of a single dose of medication followed by 72hours of pharmacokinetic sampling, with a washout of at least 7 days between treatment periods. |
| 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 |
| |||||||||||||||||
| 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 | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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| Primary | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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| Secondary | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (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. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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| Primary | Empa: Maximum Measured Concentration (Cmax) | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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| Primary | Metformin: Maximum Measured Concentration (Cmax) | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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| Secondary | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (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. In this endpoint, the "Measured values" shows inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | Pharmacokinetic (PK) set: All subjects who took at least 1 dose of investigational treatment, provided at least 1 observation for at least 1 primary PK endpoint, did not have important protocol violations relevant to the evaluation of relative bioavailability, did not vomit at or before 2 times median tmax and did not use restricted medications | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
|
Treatment period and following washout period, up to 35 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 | Empa 12.5mg Fixed-dose | Fixed-dose tablet of 12.5mg empagliflozin plus 850mg metformin | 0 | 35 | 14 | 35 | ||
| EG001 | Empa 12.5mg Free Dose | Free dose combination of 12.5mg empagliflozin (consisting of 1 tablet of 10mg and another of 2.5mg) and 850mg metformin (1 tablet) | 0 | 36 | 13 | 36 | ||
| EG002 | Empa 5mg Fixed-dose | Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin | 0 | 34 | 14 | 34 | ||
| EG003 | Empa 5mg Free Dose | Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) | 0 | 35 | 9 | 35 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Nasopharyngitis | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MEDDRA 15.1 | Systematic Assessment |
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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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| ANOVA | Based on an ANOVA including the random effect subjects within sequences and the fixed effects sequence, period and treatment. | Geometric Mean Ratio | 100.30 | Standard Deviation | 7.0 | 2-Sided | 90 | 97.40 | 103.29 | Standard deviation is actually the geometric coefficient of variation (gCV) | Yes | Non-Inferiority or Equivalence | Considered characteristic is empa 5mg fixed-dose divided by empa 5mg free dose |
Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
| OG003 | Empa 5mg Free Dose | Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) |
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Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
| OG003 | Empa 5mg Free Dose | Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) |
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| OG003 | Empa 5mg Free Dose | Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) |
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| OG003 | Empa 5mg Free Dose | Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) |
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Fixed-dose tablet of 5mg empagliflozin plus 850mg metformin
| OG003 | Empa 5mg Free Dose | Free dose combination of 5mg empagliflozin (1 tablet) and 850mg metformin (1 tablet) |
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