A Study in Healthy Humans to Assess the Relative Bioavailability of One Fixed-dose Combination Tablet Empagliflozin/Metformin Versus Jardiance® Tablet and Glifage® Tablet Administered Together
Study Details
Study Description
Brief Summary
This trial is to establish bioequivalence of the fixed dose combination (FDC) tablets (containing 12.5 mg empagliflozin/850 mg metformin) (Test, T) compared with the single tablets (10 mg empagliflozin and Glifage® 850 mg tablets) (Reference, R).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Test: empagliflozin/metformin, fixed dose combination
|
Drug: empagliflozin/metformin
empagliflozin/metformin
|
| Active Comparator: Reference: Jardiance® and Glifage® single dose each
|
Drug: Jardiance®
Jardiance®
Other Names:
Drug: Glifage®
Glifage®
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Dose-normalized area under the curve from the time of dosing (Dosing_time) to the last measurable (positive) concentration of empagliflozin. [up to 14 days]
- Maximum observed concentration of empagliflozin, occurring at Tmax. If not unique, then the first maximum is used. [up to 14 days]
Tmax = Time of maximum observed concentration of empagliflozin. For non-steady-state data, the entire curve is considered. For steady-state data, Tmax corresponds to points collected during a dosing interval. If the maximum observed concentration is not unique, then the first maximum is used.
- Area under the curve from the time of dosing (Dosing_time) to the last measurable (positive) concentration of metformin. [up to 14 days]
- Maximum observed concentration of metformin, occurring at Tmax. If not unique, then the first maximum is used. [up to 14 days]
Tmax = Time of maximum observed concentration of metformin. For non-steady-state data, the entire curve is considered. For steady-state data, Tmax corresponds to points collected during a dosing interval. If the maximum observed concentration is not unique, then the first maximum is used.
Secondary Outcome Measures
- Dose-normalized area under the curve from Dosing_time extrapolated to infinity, based on the last observed concentration of empagliflozin. [up to 14 days]
- Area under the curve from Dosing_time extrapolated to infinity, based on the last observed concentration of metformin. [up to 14 days]
- Time of maximum observed concentration of empagliflozin and metformin. [up to 14 days]
For non-steady-state data, the entire curve is considered. For steady-state data, Tmax corresponds to points collected during a dosing interval. If the maximum observed concentration is not unique, then the first maximum is used.
- Percentage of Area under the curve from Dosing_time extrapolated to infinity, based on the last observed concentration (obs) due to extrapolation from Tlast to infinity of empagliflozin and metformin. [up to 14 days]
- Terminal half-life of first order rate constant associated with the terminal (log-linear) portion of the curve. Estimated by linear regression of time vs. log concentration of empagliflozin and metformin. [up to 14 days]
- First order rate constant associated with the terminal (log-linear) portion of the curve. Estimated by linear regression of time vs. log concentration of empagliflozin and metformin. [up to 14 days]
Eligibility Criteria
Criteria
Inclusion criteria:
-
Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
-
Age of at least 18 (inclusive) to 50 years (inclusive)
-
Body mass index (BMI) of 18.5 to 29.9 weight divided by height squared (kg/m2) (inclusive)
-
Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
-
Male subjects, or female subjects who meet any of the following criteria from at least 30 days before the first administration of trial medication until 30 days after trial completion:
-
Use of adequate contraception, e.g. any of the following methods plus condom:
-
implants, injectables, combined oral or vaginal contraceptives, intrauterine device
-
Sexually abstinent
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A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
-
Surgically sterilised (including hysterectomy)
Exclusion Criteria:
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Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator
-
Repeated measurement of systolic blood pressure outside the range of 90 to 140 millimetre of mercury (mmHg), diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
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Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
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Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
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History of relevant orthostatic hypotension, fainting spells, or blackouts
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Chronic or relevant acute infections
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Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause time from the start of the Q wave to the end of the T wave (QT) / corrected QT (QTc) interval prolongation)
-
Smoker (more than 5 cigarettes or 1 cigar or 1 pipe per day)
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Detection or indeterminate / inconclusive result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Coronavirus ribonucleic acid (RNA) in the quantitative real-time polymerase chain reaction (RT-qPCR) exam performed on the day before the admission of each period;
-
The research participant presents symptoms of coronavirus disease 2019 (COVID-19) infection (even if the result is "undetected" in the RT-PCR exam for COVID-19)
-
Further exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Instituto de Ciências Farmacêuticas de Estudos e Pesquisas - ICF | Goiânia | Brazil | 74935-530 |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 1276-0041