Fasting Bioequivalence Study of 2 Metformin 500 mg Prolonged Release Tablets in 44 Healthy Male and Female Volunteers

• Status: Completed
• Trial end date: 2021-05-29
• Target enrollment: 0
• Participant gender: All

Summary

This study was designed to compare the bioavailability of the Test Product Metformin 500mg Prolonged Release Tablets (JSC Farmak, Ukraine) and Reference Product Glucophage® XR 500 mg Prolonged Release Tablets (Merck Serono Ltd, UK) in healthy male and female volunteers under fasting conditions.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Joint Stock Company "Farmak"
• Treatments: Metformin

Criteria

Inclusion Criteria:

• Healthy males and non-pregnant and no breast-feeding females (must have a negative pregnansy test result prior to dosing). Caucasian race.

• Non-smoker or past-smoker (who has stopped smoking at least 6 months before the first dosing).

• Body Mass Index (BMI) 18.5 to 30.0 kg/m2, inclusive and body weight between 50 kg and 100 kg (on the day of screening).

• Subject was available for the whole study and has provided his/her written informed consent.

• Subjects in good health, as determined by screening medical history, physical examination, vital signs assessments (pulse rate, systolic and diastolic blood pressure, and body temperature) and 12-lead ECG. Minor deviations outside the reference ranges were acceptable, if deemed not clinically significant by the Investigator.

• All laboratory screening results within the normal range. Minor deviations outside the reference ranges were acceptable, if deemed not clinically significant by the Clinical Investigator.

• Acceptance of use of contraceptive measures during the whole study by both female and male subjects.

Exclusion Criteria:

• Known cardiovascular disease, history of hypotension.

• Factors in the subject's history that may predispose to ketoacidosis (including pancreatic insulin deficiency, history of pancreatitis, caloric restriction disorders, restricted food intake, alcohol abuse).

• Gastrointestinal, renal or hepatic diseases and/or pathological findings present or in history, which might interfere with the drug pharmacokinetics.

• Glucose level out of the limit 3.3 mmol/L - 5.5 mmol/Lat screening, as determined by screening clinical laboratory evaluations.

• Previous liver disease or clinically significant elevations in serum transaminases at the screening.

• Acute or chronic diseases and/or clinical finding which may interfere with the aims of the study or with the drug's safety, tolerability, bioavailability and/or pharmacokinetics of the IMP.

• History of kidney disease and with impaired renal function.

• History of severe allergy or allergic reactions to the study IMP, its excipients or related drugs.

• Clinically significant illness within 28 days before the first dosing, including major surgery.

• Any significant clinical abnormality including Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), and / or (human immunodeficiency virus) HIV. (On screening).

• Positive result of blood pregnancy test at screening or positive urine pregnancy test at check-in or breast-feeding or lack of results of pregnancy test.

• Positive results of drugs of abuse in urine at screening and at check-in.

• Positive result of alcohol breath test at screening and at check-in.

• Positive result of urine cotinine test at screening and at check-in.

• Serious mental disease and/or inability to cooperate with clinical team.

• Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of 90-140 mmHg for systolic blood pressure (BP) and/or 60-90 mmHg for diastolic BP and/or heart rate out of the range of 50-100 bpm during the screening procedure.

• Body ear temperature is out of the range of 35.7 - 37.3°C at screening and at check-in.

• Orthostatic hypotension during the screening procedure.

• Drug, alcohol (of ≥ 40 g per day pure ethanol), solvents or caffeine abuse.

• Use of organ-toxic drugs or systemic drugs known to substantially alter liver metabolism within 90 days before the first dosing.

• Use of any prescription medication for a period of 28 days before the first dosing.

• Use of any OTC (over-the-counter) medication including vitamins, herbal medications and food supplements less than 14 days before the first dosing.

• Getting a tattoo, body piercing or any cosmetic treatment involving skin piercing within 90 days before the screening unless evaluated by Investigator as non-significant for inclusion in the study.

• Donation or loss of at least 500 mL of blood within 90 days or donation of plasma or platelets within 14 days before the first dosing.

• Anemia, haemoglobin below 120 g/L for women and 130 g/L for men at screening.

• Less than 30 days between exit procedure in previous study and the first dosing in in this study.