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The trial is being conducted to establish the bioequivalence of emp/met (12.5mg/500mg) fixed dose combination tablets compared to tablets administered together in healthy male and female volunteers under fed conditions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fixed Dose Combination (FDC) | Experimental | 12.5 mg Empagliflozin / 500mg metformin fixed dose combination |
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| Separate tablets | Active Comparator | Empagliflozin and Metformin tablets |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Empagliflozin 2.5 mg | Drug | Empagliflozin 2.5 mg tablet |
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| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-tz) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) | AUC (0-tz) (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
| Cmax (Maximum Measured Concentration of Metformin in Plasma) | Cmax (maximum measured concentration of metformin in plasma) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0-infinity) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | AUC (0-infinity) (Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity) | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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Inclusion criteria:
Exclusion criteria:
Any finding in the medical examination (Including blood pressure [BP], pulse rate [PR], or electrocardiogram [ECG]) deviating from normal and judged clinically relevant by the investigator.
Any evidence of a concomitant disease judged clinically relevant by the investigator.
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders.
Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug(s)
Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders.
History of relevant orthostatic hypotension, fainting spells, or blackouts.
Chronic or relevant acute infections
History of relevant allergy/hypersensitivity (including allergy to the trial medication or it's excipients)
Intake of drugs with a long half-life (>24 hours) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication.
Within 14 days prior to the administration of trial medication, use of drugs that might reasonably influence the results of the trial, based on current knowledge
Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication.
Smoker (has used tobacco or nicotine-containing products within 6 months prior to administration of trial medication)
Inability to refrain from smoking on specified trial days
Alcohol abuse (consumption of more than 20g/day in females and 30g/day in males or > 7 alcohol-containing drinks per week)
Drug abuse or positive drug screen
Blood donation (more than 100 ml wihtin 30 days prior to administration of trial medication or intended during the trial)
Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
Inability to comply with dietary regimen of trial site
Subject is assessed by the investigator as unsuitable for inclusion, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study.
For female subjects:
Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion.
No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent, surgically sterile, or post menopausal will be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide). Post-menopausal is defined as at least 1 year of spontaneous amenorrhea and deemed post menopausal by a physician based on screening clinical laboratory tests (follicle stimulating hormone and luteinizing hormone).
Lactation
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1276.24.001 Boehringer Ingelheim Investigational Site | Toronto | Ontario | Canada |
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| ID | Title | Description |
|---|---|---|
| FG000 | Fixed Dose Combination (FDC) First, Then Separate Tablets | Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin first, then free combination of Empagliflozin 2.5 mg tablet, Empagliflozin 10 mg tablet and Metformin 500 mg tablet Both medications were administered oral with 240 mL water after intake of a high-fat, high-calorie meal. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| Empagliflozin 10 mg |
| Drug |
Empagliflozin 10 mg tablet |
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| Metformin 500 mg | Drug | Metformin 500 mg tablet |
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| Empagliflozin/Metformin FDC | Drug | 12.5 mg Empagliflozin / 500 mg Metformin |
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| FG001 |
| Separate Tablets First, Then Fixed Dose Combination (FDC) |
free combination of Empagliflozin 2.5 mg tablet, Empagliflozin 10 mg tablet and Metformin 500 mg tablet first, then Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin Both medications were administered oral with 240 mL water after intake of a high-fat, high-calorie meal. |
| COMPLETED |
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| NOT COMPLETED |
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| Treatment Period 2 |
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Treated set (TS): includes all subjects who were dispensed study medication and were documented to have received at least 1 dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Fixed Dose Combination vs. Separate Tablets | 12.5 mg Empagliflozin / 500mg metformin fixed dose combination vs. free combination of 2.5 mg tablet Empagliflozin, 10 mg tablet Empagliflozin and 500 mg tablet Metformin |
| 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 | AUC (0-tz) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) | AUC (0-tz) (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point) | Pharmacokinetic set (PKS): includes all subjects of the TS who provided at least 1 observation for at least 1 primary pharmacokinetic endpoint, and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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| Primary | Cmax (Maximum Measured Concentration of Metformin in Plasma) | Cmax (maximum measured concentration of metformin in plasma) | PKS: includes all subjects of the TS who provided at least 1 observation for at least 1 primary pharmacokinetic endpoint, and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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| Secondary | AUC (0-infinity) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity) | AUC (0-infinity) (Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity) | PKS: includes all subjects of the TS who provided at least 1 observation for at least 1 primary pharmacokinetic endpoint, and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |
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From first trial medication intake until next intake or the day after the end-of-trial visit, 16 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 | Fixed Dose Combination (FDC) | 12.5 mg Empagliflozin / 500mg metformin fixed dose combination Empagliflozin / Metformin FDC: 12.5 mg Empagliflozin / 500 mg Metformin | 0 | 32 | 11 | 32 | ||
| EG001 | Separate Tablets | Empagliflozin and Metformin tablets Empagliflozin 2.5 mg: Empagliflozin 2.5 mg tablet Empagliflozin 10 mg: Empagliflozin 10 mg tablet Metformin 500 mg: Metformin 500 mg tablet | 0 | 30 | 5 | 30 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
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Other - 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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| Analysis with fixed effects for all terms | ANOVA | <0.0001 | The p-value relates to the null hypothesis of non-equivalence. | Geometric mean ratio | 98.71 | Standard Error of the Mean | 1.024 | 2-Sided | 90 | 94.783 | 102.796 | The geometric mean ratio is the exponential of the estimated mean difference on the log-scale between 'FDC' and 'Separate tablets'. ANOVA on the log-scale: sequence, subjects within sequences, period and treatment as fixed effects | Yes | Non-Inferiority or Equivalence | Bioequivalence test |
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