Fasting Bioequivalence Study of 2 Metformin 1000 mg Prolonged Release Tablets in 28 Healthy Male and Female Volunteers

NCT05123781 | Completed Phase 1

• 1 other identifier: FK/MTF/FS
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective was to compare the rate and extent of absorption of Metformin XR after administration of a Test Product Metformin 1000 mg Prolonged Release Tablets (JSC Farmak, Ukraine) and Reference Product Glucophage® XR 1000 mg Prolonged Release Tablets (Merck Serono Ltd, UK), administered as a single dose in healthy subjects under fasting conditions. The adverse events, physical examinations and vital signs were reported for the evaluation of safety.

Conditions

Pharmacokinetics

Keywords

bioequivalence; pharmacokinetics; generic drugs; Metformin 1000 mg Prolonged Release Tablets; Prolonged Release Tablets; oral dosage form; Metformin

Outcome Measures

Primary Outcomes (2)

• AUC0-t

  area under the plasma drug concentration

  up to 36 hours post-administration

• Cmax

  maximum plasma concentration observed.

  up to 36 hours post-administration

Secondary Outcomes (8)

• AUC(0-∞)

  up to 36 hours post-administration

• AUC(0-12h)

  from time zero to time 12 hours after dosing

• AUC(12h-t)

  from time 12 hours after dosing to time of the last sample above LLOQ.

• AUC(0-24h)

  from time zero to time 24 hours after dosing

• tmax

  up to 36 hours post-administration

Study Arms (2)

Treatment A

EXPERIMENTAL

Test Product Metformin 1000 mg Prolonged Release Tablets (JSC Farmak, Ukraine)

Drug: Metformin 1000 mg Prolonged Release Tablets (JSC Farmak, Ukraine)

Treatment B

ACTIVE COMPARATOR

Reference Product Glucophage® XR 1000 mg Prolonged Release Tablets (Merck Serono Ltd, UK)

Drug: Glucophage® XR 1000 mg Prolonged Release Tablets (Merck Serono Ltd, UK)

Interventions

Metformin 1000 mg Prolonged Release Tablets (JSC Farmak, Ukraine) DRUG

One tablet of the test product was administered orally with 240 ml of water

Also known as: Diaformin® SR 1000mg tablets (JSC Farmak, Ukraine), Diabufor® XR 1000mg tablets (JSC Farmak, Ukraine)

Treatment A

Glucophage® XR 1000 mg Prolonged Release Tablets (Merck Serono Ltd, UK) DRUG

One tablet of the Reference product was administered orally with 240 ml of water

Also known as: Glucophage® XR 1000 mg

Treatment B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and non-pregnant and no breast-feeding females (must have a negative pregnancy 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 is 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 will be acceptable, if deemed not clinically significant by the Investigator.
• Subjects in good health and with glucose between 3.3 mmol/L-5.5 mmol/l at screening, as determined by screening clinical laboratory evaluations. Minor deviations outside the reference ranges will be acceptable, if deemed not clinically significant by the Investigator. 7. Acceptance of use of contraceptive measures during the whole study by both female and male subjects

You may not qualify if:

• Known cardiovascular disease, history of hypotension.
• Factors in the subject's history that may predispose to ketoacidosis and lactic acidosis or all types of the metabolic acidosis (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.
• Previous liver disease or elevations in serum transaminases ALT or AST ≥1.0 ULN at the screening (for women 0-0.52 µmol/L and for men 0-0.68 µmol/L).
• 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 with impaired renal function and level of creatinine out of the normal laboratory range based on screening.
• 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 a positive result of HBsAg and/or HCV and/or HIV test during screening procedure.
• Positive screening urine drugs abuse test or/and alcohol breath test or urine cotinine test, and positive pregnancy test on screening.
• 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 100-140 mmHg for systolic BP and/or 60-100 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 35.7-37.6°C at screening.
• Orthostatic hypotension during the screening procedure.
• Drug, alcohol (of ≥ 40 g per day pure ethanol), solvents or caffeine abuse.

Sponsors & Collaborators

• Joint Stock Company "Farmak": lead

Study Sites (1)

QUINTA-ANALYTICA s.r.o.

Prague, 10200, Czechia

Location

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Vlad Udovytskyi

  Joint Stock Company "Farmak"

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: November 17, 2021
• Study Start: April 3, 2019
• Primary Completion: April 17, 2019
• Study Completion: April 17, 2019
• Last Updated: November 17, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)