Clinical trial NCT05125575: Fed Bioequivalence Study of 2 Metformin 1000 mg Prolonged Release Tablets in 28 Healthy Male and Female Volunteers
Official title: Open, Comparative, Randomized, Crossover, Single Dose Bioequivalence Study of Metformin 1000 mg Prolonged Release Tablets (JSC Farmak, Ukraine) vs Glucophage® XR 1000 mg Prolonged Release Tablets in Healthy Subjects Under Fed Conditions.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Keywords: bioequivalence
pharmacokinetics
generic drugs
Metformin 1000 mg Prolonged Release Tablets
Metformin
Prolonged Release Tablets
Lead sponsor: Joint Stock Company "Farmak"
Sponsor class: INDUSTRY
First posted: 2021-11-18
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This study was designed to compare the bioavailability of the 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) in healthy male and female volunteers under fed conditions.

Detailed description: An Open, Comparative, Randomized, Crossover Clinical Trial to Evaluate the Bioequivalence of Single Doses of 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) in Healthy, Adult Male and Female Subjects Under Fed Conditions.

During each period 21 blood samples were taken: prior to dosing (-1.0) and 1.0, 2.0, 3.0, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 10.0, 12.0, 16.0, 24.0, 32.0 and 36.0 hours after IMP administration.

Eligibility criteria: Inclusion Criteria:

* 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 was available for the whole study and had 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 (electrocardiogram). Minor deviations outside the reference ranges were acceptable, if deemed not clinically significant by the Investigator.
* Subjects in good health, as determined by screening clinical laboratory evaluations. Minor deviations outside the reference ranges were acceptable, if deemed not clinically significant by the 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 might 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.
* Previous liver disease with elevations in serum transaminases.
* Acute or chronic diseases and/or clinical finding which might interfere with the aims of the study or with the drug's safety, tolerability, bioavailability and/or pharmacokinetics of the Investigational Medicinal Product (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 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 blood pressure (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 was 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.
* 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.
* Any systemic over-the-counter (OTC) drug treatment and/or vitamins and/or herbal treatment/or food supplements within 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.
* Anaemia, 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 this study.

Primary outcomes:
measure: Cmax
timeFrame: up to 36 hours post-administration
measure: AUC0-t
timeFrame: up to 36 hours post-administration
Secondary outcomes:
measure: AUC0-∞
timeFrame: up to 36 hours post-administration
measure: tmax
timeFrame: up to 36 hours post-administration
measure: λz
timeFrame: up to 36 hours post-administration
measure: t1/2
timeFrame: up to 36 hours post-administration
measure: AUCres
timeFrame: up to 36 hours post-administration
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: QUINTA-ANALYTICA s.r.o.
Study officials:
affiliation: Joint Stock Company "Farmak"
name: Vlad Udovytskyi
role: STUDY_CHAIR
References: