Exploratory Bioavailability of Two Formulations of Gliclazide MR Tablets 120 mg (I.R.I.S.) in Healthy Volunteers Under Fed and Fasting Conditions.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

7 Nov 2023 → 20 Dec 2023

Decision date (initial)

2023-11-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Institut De Recherches Internationales Servier IRIS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic

1. To evaluate the pharmacokinetics in plasma and the relative bioavailability of Gliclazide MR 120 mg tablets (I.R.I.S.), developed as Test A and Test B with three different releasing rates (slow, medium, and fast release rate), and two Diamicron® MR 60 mg tablets (I.R.I.S.), after a single oral administration under fasting conditions.
2. To evaluate the pharmacokinetics in plasma and the relative bioavailability of Gliclazide MR 120 mg tablets (I.R.I.S.) developed as Test A and Test B with a medium releasing rate, and two Diamicron® MR 60 mg tablets (I.R.I.S.) under fed conditions.

Secondary objectives 2

1. To support the development of a level A In Vitro-In Vivo Correlation (IVIVC) for Gliclazide MR 120 mg tablets.
2. To assess the safety and tolerability of the investigational products.

Conditions and MedDRA coding

Type 2 diabetes mellitus

Study design 2 periods

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Free written informed consent prior to any procedure required by the study.
2. Willingness to accept and comply with all study procedures and restrictions and availability for the duration of the study.
3. Male or female subject between 18 and 50 years, inclusive, at the time of signing the informed consent.
4. Body weight ≥50 kg for male and ≥48 kg for female participants, and body mass index (BMI) within 18.5 to 30.0 kg/m2, inclusive.
5. No clinically relevant diseases captured in medical history, as judged by the Investigator.
6. No clinically relevant abnormalities on physical examination, as judged by the Investigator.
7. No clinically relevant abnormalities on vital signs, as judged by the Investigator.
8. No clinically relevant abnormalities on 12-lead ECG, as judged by the Investigator.
9. No clinically relevant abnormalities on clinical laboratory tests (clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without clinical significance, as determined by an investigator).
10. Negative serology for HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAg), Hepatitis B core antibody (anti-HBc), or Hepatitis C Virus (HCV) antibody.
11. 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).
12. If woman, meets one of the following criteria: a) is of non-childbearing potential; b) is of childbearing potential and agrees to use an accepted non-hormonal or hormonal contraceptive method, since at least 4 weeks prior to admission to the first study period until 4 weeks after the last study drug administration.
13. If man, infertile, vasectomized (i.e., who has received medical assessment of the surgical success) or willing to comply with the following contraception requirements from the first up to 4 weeks after the last study drug administration: a) Abstinence of heterosexual intercourse (when this is in line with preferred and usual lifestyle of the subject). b) Barrier method (preferably male condom) during heterosexual intercourse, when the female partner is of childbearing potential.
14. If man, willingness to not donate sperm during the course of the study and until 3 months (90 days) after the last study drug administration.

Exclusion criteria 35

1. Known hypersensitivity/allergy reaction to the study drug substance or any of the excipients.
2. Known 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 documented hypoglycemia.
6. History of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
7. History of endocrine diseases.
8. Had major surgery within the past 30 days prior to study drug administration or planning to have major surgery within 30 days after the last study drug administration.
9. History of drug or alcohol abuse.
10. Blood hemoglobin below 12.0 g/dL for females, and 13.2 g/dL for males.
11. Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) above the upper limit of 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 surface area of 1.73 m2.
13. Positive result in drugs-of-abuse, cotinine, or ethanol tests.
14. Positive result in pregnancy test.
15. Use of a depot injection or an implant of any drug (except contraceptives) within the previous 6 months.
16. Use of corticosteroids within the previous 6 months.
17. Maintenance therapy with any drug or regular use of medication in the last 30 days (except contraceptives).
18. Average weekly alcohol consumption of >14 units for males and >7 units for females within the previous 6 months.
19. Average daily xanthine consumption >5 units of caffeinated beverages.
20. Participation in any clinical trial within the previous 2 months.
21. Participation in more than 2 clinical trials within the previous 12 months.
22. Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 3 months.
23. Difficulty in fasting or any dietary restriction (such as lactose intolerance, vegan, vegetarian, low-fat, low sodium, etc.), that may interfere with the diet served during the study.
24. Difficulty in swallowing capsules or tablets.
25. Venous status at forearm or dorsal hand making it difficult to insert a venous peripheral catheter.
26. If woman, is lactating.
27. Any other condition that the Investigator considers to render the subject unsuitable for the study.
28. 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.
29. Use of any prescription or non-prescription drugs in the prior 30 days, that in the opinion of an investigator would put into question the status of the participant as healthy or is deemed to interfere with the pharmacokinetics of study drug.
30. Use of miconazole within the prior 30 days.
31. Consumption of pineapple, Seville oranges, pomelo, pomegranate, starfruit or grapefruit products (fresh, canned, or frozen) within the previous week (Period 1) or during the washout (Periods 2, 3, 4 and 5).
32. Consumption of any alcoholic product within the previous 24 hours.
33. Positive result in pregnancy test.
34. Positive result in drugs-of-abuse, cotinine, or ethanol tests.
35. 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, AUC0-t and AUC0-∞ of Gliclazide will be the primary pharmacokinetic parameters.

Secondary endpoints 2

1. tmax, tlag, Clast, tlast, t1/2, %AUCextrap and λz of Gliclazide will be the secondary pharmacokinetic parameters.
2. Safety will be evaluated through the assessment of adverse events (AEs), laboratory tests, vital signs, physical examination, and electrocardiogram (ECG).

Investigational products

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

Test 6

Comparator 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Valérie Brunet

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Regulatory Affairs & Pharmacovigilance Management

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 3 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