PharmacokineticsPhase 1NCT05124717
Fed Bioequivalence Study of 2 Metformin 500 mg Prolongued Release Tablets in 28 Healthy Male and Female Volunteers
A Phase 1 study testing Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) and Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK) in people with Pharmacokinetics, run by Joint Stock Company "Farmak" at 1 site in Czechia.
Trial summary
The objective of the study is to compare the bioavailability of the Test and Reference products both containing Metformin 500 mg prolonged release tablets (MFM) in healthy male and female volunteers under fed conditions and to assess the bioequivalence of these products based on confidence acceptance intervals of… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics
- What is being tested?
- Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) and Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteCzechia
- Study dates
- 25 Jun 2019to 3 Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 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 electrocardiogram (ECG). Minor deviations outside the reference ranges were acceptable, if were 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 were acceptable, if were deemed not clinically significant by the Investigator.
- Acceptance of use of contraceptive measures during the whole study by both female and male subjects.
Who cannot join
- 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 disoroders, 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 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.0 upper limit of normal (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 Investigational Medicinal Product (IMP).
- History of kidney disease and with impaired renal function.
Show all 25Show fewer
- 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.
- 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 35.7-37.6°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.
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open, Comparative, Randomized, Crossover Bioequivalence Study of Single Doses of Metformin, Prolonged-release Tablets 500 mg (JSC Farmak, Ukraine) vs Glucophage® XR 500 mg in Healthy, Adult Male and Female Subjects Under Fed Conditions.
The objective of the study is to compare the bioavailability of the Test and Reference products both containing Metformin 500 mg prolonged release tablets (MFM) in healthy male and female volunteers under fed conditions and to assess the bioequivalence of these products based on confidence acceptance intervals of 80.00% to 125.00% for AUC(o-t)and Cmax of MFM as primary endpoints.
Read the detailed description
An Open, Comparative, Randomized, Crossover Clinical Trial to Evaluate the Bioequivalence of Single Doses of Test Product Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) and Reference Product Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK) in Healthy, Adult Male and Female Subjects Under Fed Conditions Single oral dose of Glucophage® XR 500 mg prolonged release tablets of Reference product or Metformin, prolonged-release tablets 500 mg of Test product will be administered to volunteers under fed conditions in the morning of Day 1 of each Study Period.
Pharmacokinetic parameters of MFM were calculated from plasma concentrations determined by validated HPLC/MS/MS method.
Pharmacokinetic parameters of the Test and Reference tablets were compared.
During each period 21 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 in each study period.
The study consists of two study periods with a washout period of at least 7 days between doses.
Adverse events and clinically significant deviations from laboratory tests, physical examinations and vital signs were reported for the evaluation of safety.
- Conditions
- Pharmacokinetics
- Being tested
- Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine), Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK)
- Keywords
- bioequivalence, pharmacokinetics, generic drugs, Metformin 500 mg Prolonged Release Tablets, Prolonged Release Tablets, oral dosage form, Metformin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine)Drug
Also called Diaformin® SR 500mg tablets (JSC Farmak, Ukraine), Diabufor® XR 500mg tablets (JSC Farmak, Ukraine)
One tablet of the Test product was administered orally with 240 mL of water.
Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK)Drug
Also called Glucophage® XR 500 mg
One tablet of the Reference product was administered orallyn with 240 mL of water.
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | Test Product Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) Receives: Drug: Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) |
| Treatment B | Active comparator | Reference Product Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK) Receives: Drug: Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK) |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC(0-t)
area under the plasma drug concentration versus time curve
Measured: up to 36 hours post-administration
Cmax
maximum plasma concentration observed
Measured: up to 36 hours post-administration
Secondary outcomes (7)
AUC(0-∞)
area under the plasma drug concentration versus time curve from time zero to infinity
Measured: up to 36 hours post-administration
AUC(0-12h)
the area under the plasma drug concentration versus time curve calculated from time zero to time 12 hours after dosing
Measured: from time zero to time 12 hours after dosing.
AUC(12h-t)
the area under the plasma drug concentration versus time curve calculated from time 12 hours after dosing to time of the last sample above LLOQ.
Measured: 12 hours after dosing up to 36 hours post-administration
AUC(0-24h)
the area under the plasma drug concentration versus time curve calculated from time zero to time 24 hours after dosing.
Measured: from time zero to time 24 hours after dosing.
tmax
the time of the maximum plasma drug concentration.
Measured: up to 36 hours post-administration
λz
apparent first-order elimination
Measured: up to 36 hours post-administration
AUCres
Residual area
Measured: up to 36 hours post-administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2021
- Study start25 Jun 2019
- Primary completion3 Jul 2019
- Study completion3 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joint Stock Company "Farmak"
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vlad Udovytskyi, Study chair, Joint Stock Company "Farmak"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05124717
- Sponsor's protocol ID
- FK/MTF/FD-500
- Status last verified
- Nov 2021
- First submitted
- 9 Nov 2021
- Last updated
- 18 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Comparative, Randomized, Crossover Bioequivalence Study of Single Doses of Metformin, Prolonged-release Tablets 500 mg (JSC Farmak, Ukraine) vs Glucophage® XR 500 mg in Healthy, Adult Male and Female Subjects Under Fed Conditions.
- ClinicalTrials.gov ID
- NCT05124717
- Acronym / sponsor ID
- FK/MTF/FD-500
- Conditions
- Pharmacokinetics
- Keywords
- bioequivalence, pharmacokinetics, generic drugs, Metformin 500 mg Prolonged Release Tablets, Prolonged Release Tablets, oral dosage form, Metformin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Joint Stock Company "Farmak"Industry (pharma, biotech, devices)
- Study start
- 25 Jun 2019 (actual)
- Primary completion
- 3 Jul 2019 (actual)
- Study completion
- 3 Jul 2019 (actual)
- First posted
- 18 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the study is to compare the bioavailability of the Test and Reference products both containing Metformin 500 mg prolonged release tablets (MFM) in healthy male and female volunteers under fed conditions and to assess the bioequivalence of these products based on confidence acceptance intervals of 80.00% to 125.00% for AUC(o-t)and Cmax of MFM as primary endpoints.
Detailed description
An Open, Comparative, Randomized, Crossover Clinical Trial to Evaluate the Bioequivalence of Single Doses of Test Product Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) and Reference Product Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK) in Healthy, Adult Male and Female Subjects Under Fed Conditions Single oral dose of Glucophage® XR 500 mg prolonged release tablets of Reference product or Metformin, prolonged-release tablets 500 mg of Test product will be administered to volunteers under fed conditions in the morning of Day 1 of each Study Period.
Pharmacokinetic parameters of MFM were calculated from plasma concentrations determined by validated HPLC/MS/MS method.
Pharmacokinetic parameters of the Test and Reference tablets were compared.
During each period 21 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 in each study period.
The study consists of two study periods with a washout period of at least 7 days between doses.
Adverse events and clinically significant deviations from laboratory tests, physical examinations and vital signs were reported for the evaluation of safety.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine)Test Product Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) |
| Treatment B | Active comparator | Drug: Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK)Reference Product Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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 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 electrocardiogram (ECG). Minor deviations outside the reference ranges were acceptable, if were deemed not clinically significant by the Investigator.
Key exclusion criteria (25 listed)
- 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 disoroders, 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 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥1.0 upper limit of normal (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 Investigational Medicinal Product (IMP).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine)Also: Diaformin® SR 500mg tablets (JSC Farmak, Ukraine), Diabufor® XR 500mg tablets (JSC Farmak, Ukraine)One tablet of the Test product was administered orally with 240 mL of water. | Drug | Treatment A |
| Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK)Also: Glucophage® XR 500 mgOne tablet of the Reference product was administered orallyn with 240 mL of water. | Drug | Treatment B |
Primary outcome
AUC(0-t)
Time frame: up to 36 hours post-administration
area under the plasma drug concentration versus time curve
Cmax
Time frame: up to 36 hours post-administration
maximum plasma concentration observed
7 secondary outcomes
AUC(0-∞)
Time frame: up to 36 hours post-administration
AUC(0-12h)
Time frame: from time zero to time 12 hours after dosing.
AUC(12h-t)
Time frame: 12 hours after dosing up to 36 hours post-administration
AUC(0-24h)
Time frame: from time zero to time 24 hours after dosing.
tmax
Time frame: up to 36 hours post-administration
λz
Time frame: up to 36 hours post-administration
AUCres
Time frame: up to 36 hours post-administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vlad Udovytskyi study chair
Joint Stock Company "Farmak"
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin, prolonged-release tablets 500 mg (JSC Farmak, Ukraine) and Glucophage® XR 500 mg prolonged release tablets (Merck Serono Ltd, UK) in people with Pharmacokinetics, run by Joint Stock Company "Farmak" at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC(0-t) (time frame: up to 36 hours post-administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2021.