Comparative Bioavailability of Empagliflozin 25 mg Film-Coated Tablets: A Single-Dose, Open-Label, Randomized, Two-Sequence, Two-Treatment, Two-Period Crossover Study in Healthy Subjects Under Fasting Conditions.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tecnimede-Sociedade Tecnico-Medicinal S.A.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

11 Sep 2023 → 30 Sep 2023

Decision date (initial)

2023-08-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Tecnimede, Sociedade Técnico Medicinal, S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Bioequivalence

Compare the bioavailability of Tecnimede’s Empagliflozin 25 mg film-coated tablets (Test product) with Jardiance® 25 mg film-coated tablets (Reference product).

Secondary objectives 2

1. Evaluate the pharmacokinetic profile of Empagliflozin 25 mg following a single-dose administration of Test and Reference products
2. To assess the safety and tolerability of the investigational products (Test and Reference products).

Conditions and MedDRA coding

No medical condition

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Free written informed consent prior to any procedure required by the study.
2. Male or female subject between 18 and 55 years, inclusive, at the time of signing the informed consent.
3. Body mass index (BMI) of 18.5 to 30.0 kg/m2, inclusive.
4. No clinically relevant diseases captured in medical history.
5. No clinically relevant abnormalities on physical examination.
6. No clinically relevant abnormalities on 12-lead ECG.
7. No clinically relevant abnormalities on clinical laboratory tests.
8. Negative test results for anti-Human Immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAG) and anti-Hepatitis C virus antibodies (anti-HCVAb)
9. Non-smoker or ex-smoker (i.e., someone who abstained from using tobacco- or nicotine-containing products for at least 3 months prior to Screening)
10. Willingness to accept and comply with all study procedures and restrictions.
11. A female subject is eligible if she meets one of the following criteria: a) is of non-childbearing potential; or b) is of childbearing potential and agrees to use an accepted contraceptive method from at least 4 weeks prior to admission to the first study period until 2 weeks after the end of the study.

Exclusion criteria 32

1. Known hypersensitivity / allergy reaction to the study drug substance or any of the excipients of the investigational medicinal products (lactose monohydrate, microcrystalline cellulose, hydroxypropylcellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, Hypromellose, calcium carbonate, titanium dioxide [E171], talc, macrogol [400], iron oxide yellow [E172]).
2. Known rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
3. Known severe hypersensitivity reaction to any other drug.
4. Any medical condition (e.g., gastrointestinal, renal or hepatic, including peptic ulcer, inflammatory bowel disease or pancreatitis) or surgical condition (e.g., cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.
5. History of diabetes.
6. History of cardiovascular disease.
7. History of pancreatitis.
8. History of renal or hepatic impairment.
9. History of orthostatic hypotension, collapse, fainting, syncope, or vasovagal reaction.
10. Systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <45 mmHg, measured on the dominant arm, after at least 3 minutes in seated position.
11. Serum transaminases alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of the normal range.
12. Estimated renal creatinine clearance (CLCr) below the lower limit of normal range, based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average body surface area of 1.73 m2.
13. Positive result in drugs-of-abuse or ethanol tests.
14. Use of a depot injection or an implant of any drug (except for contraceptives) within the previous 6 months.
15. Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
16. Average daily consumption of methylxanthines-containing beverages or food (e.g., coffee, tea, cola, sodas, chocolate) equivalent to >500 mg of methylxanthines.
17. Participation in any clinical trial within the previous 2 months.
18. Participation in more than 2 clinical trials within the previous 12 months.
19. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
20. Difficulty in fasting or any dietary restriction such as lactose intolerance, vegan, low-fat, low sodium, etc., that may interfere with the diet served during the study.
21. Veins unsuitable for intravenous puncture on either arm.
22. Difficulty in swallowing capsules or tablets.
23. If woman, positive pregnancy test in serum.
24. If woman, she is breast-feeding.
25. Any other condition that the Investigator considers to render the subject unsuitable for the study.
26. Any recent disease or condition or treatment that, according to the Investigator, would put the subject at undue risk due to study participation or occurred at a timeframe in which may interfere with the pharmacokinetics of study drug.
27. Use of prescription or nonprescription medicinal products, vitamins, food supplements or herbal supplements (including St John’s Wort) within the previous 2 weeks, unless in the Investigator’s opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety.
28. Positive result in drugs-of-abuse or ethanol tests.
29. Consumption of products containing xanthines (for example, coffee, tea, chocolate, cola beverages and energy drinks) within the previous 48 hours before each study drug administration.
30. Consumption of pineapple, Seville oranges, pomelo, pomegranate, starfruit or grapefruit products (fresh, canned, or frozen) within the previous week.
31. If woman, positive pregnancy test in serum or urine.
32. Any other condition that the investigator considers to render the subject unsuitable for the study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cmax and AUC0-t of Empagliflozin.

Secondary endpoints 2

1. tmax, t1/2, AUC0-∞, %AUCextrap, λz of Empagliflozin.
2. Occurrence of treatment-emergent adverse events (TEAEs), including clinically relevant abnormalities from clinical laboratory tests and vital signs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tecnimede-Sociedade Tecnico-Medicinal S.A.

Sponsor organisation

Tecnimede-Sociedade Tecnico-Medicinal S.A.

Address

Rua Da Tapada Grande 2 Abrunheira, Rua Da Tapada Grande 2 Rua Da Tapada Grande 2

City

Sintra

Postcode

2710-228

Country

Portugal

Scientific contact point

Organisation

Tecnimede-Sociedade Tecnico-Medicinal S.A.

Contact name

Rita Neves

Public contact point

Organisation

Tecnimede-Sociedade Tecnico-Medicinal S.A.

Contact name

Rita Neves

Third parties 4

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications