Clinical trial NCT02028767: Bioequivalence Study in Healthy Volunteers for Empagliflozin/Metformin Fixed Dose Combination Compared to Separate Tablets
Official title: Bioequivalence of Empagliflozin/Metformin (12.5mg/500mg) Fixed Dose Combination Tablets Compared to Tablets Administered Together in Healthy Male and Female Volunteers Under Fed Conditions (an Open Label, Randomised, Single Dose, Two Period, Two Sequence Crossover Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-01-07
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion criteria:

1. Healthy males or females according to the investigator's assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests.
2. Age 18 to 50 years (inclusive)
3. BMI 18.5 to 29.9 kg/m2 (inclusive)
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation.

Exclusion criteria:

1. 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.
2. Any evidence of a concomitant disease judged clinically relevant by the investigator.
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders.
4. Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug(s)
5. Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders.
6. History of relevant orthostatic hypotension, fainting spells, or blackouts.
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to the trial medication or it's excipients)
9. 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.
10. 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
11. Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication.
12. Smoker (has used tobacco or nicotine-containing products within 6 months prior to administration of trial medication)
13. Inability to refrain from smoking on specified trial days
14. Alcohol abuse (consumption of more than 20g/day in females and 30g/day in males or \> 7 alcohol-containing drinks per week)
15. Drug abuse or positive drug screen
16. Blood donation (more than 100 ml wihtin 30 days prior to administration of trial medication or intended during the trial)
17. Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
18. Inability to comply with dietary regimen of trial site
19. 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:
20. Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion.
21. 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).
22. Lactation

Primary outcomes:
measure: 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)
timeFrame: 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: Cmax (Maximum Measured Concentration of Metformin in Plasma)
timeFrame: 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
Secondary outcomes:
measure: AUC (0-infinity) (Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
timeFrame: 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
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: 1276.24.001 Boehringer Ingelheim Investigational Site
state: Ontario
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: