Metformin XR BE Study in Healthy Volunteers With Single and Multiple DoseNCT01677260
Bioequivalence Study of Two Formulations of 500 mg Metformin Extended Release Tablet
A study testing 500 mg metformin hydrochloride extended release caplet (test drug) and 500 mg metformin hydrochloride prolonged release tablet (reference drug) in people with Metformin XR BE Study in Healthy Volunteers With Single and Multiple Dose, run by Dexa Medica Group at 1 site in Indonesia.
Trial summary
This was a single centre, single-blind, randomized, balanced, combined single dose study under fasting condition and multiple doses study under fed condition with normal diabetic-meal, two-period, two-sequence cross-over study to to compare the bioavailability of metformin hydrochloride 500 mg extended release caplet… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Metformin XR BE Study in Healthy Volunteers With Single and Multiple Dose
- What is being tested?
- 500 mg metformin hydrochloride extended release caplet (test drug) and 500 mg metformin hydrochloride prolonged release tablet (reference drug)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteIndonesia
- Study dates
- Oct 2009to Jan 2010
- Phase
- Interventional
- 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
- Male and female subjects with absence of significant diseases or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening.
- Age of 18 - 55 years
- Preferably non-smokers or smoke less than 10 cigarettes per day
- Able to participate, communicate well with the investigators and willing to provide written informed consent to participate in the study.
- BMI 18 - 25 kg/m2
- Vital signs (after 10 minutes rest) were within the following ranges:
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- SBP 100 - 120 mmHg
- DBP 60 - 80 mmHg
- Pulse rate 60 - 90 bpm
Who cannot join
- Personal/family history of allergy or hypersensitivity or contraindication to metformin hydrochloride or other biguanides and allied drug.
- Pregnant or lactating women and women of childbearing potential without adequate contraception
- Any major illnesses in the past 90 days or clinically significant ongoing chronic medical illnesses
- Clinically significant illness within 4 weeks prior to the administration of study medication
- Presence of any clinically significant abnormal values during screening
- Positive Hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV
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- Clinically significant haematology abnormalities
- Clinically significant electrocardiogram (ECG) abnormalities
- Any surgical or medical condition (present or history) which might significantly alter the absorption, distribution, metabolism or excretion of the study drug
- History of drug (cocaine, amphetamines, opiates, cannabis) or alcohol abuse within 12 months prior to screening for this study
- Participation in any clinical trial within the past 90 days
- History of any bleeding or coagulative disorders
- History or presence of asthma bronchial or related bronchospastic conditions
- History of seizures, epilepsy or any kind of neurological disorders
- History of difficulty with donating blood or difficulty in vein puncture of left or right arm
- A donation or loss of 500 mL (or more) of blood within 3 months before this study's first dosing day
- Intake of any prescription or non-prescription drugs, food supplements or herbal medicines within 14 days of this study's first dosing day
- Any food allergy, intolerance, restriction or special diet that in the opinion of the Research Physician, could contraindicate the subject's participation in this study
- Any reason in the opinion of the Research Physician, would prevent the subject from participating in the study
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
PT Equilab International
Jakarta, Jakarta Special Capital Region, 12430
About this study
Official title: A Combined Single Dose Study Under Fasting Condition And Multiple Doses Study Under Normal Diabetic Meal Comparing the Bioavailability of Two Formulations of 500 mg Metformin Hydrochloride Extended Release Tablets.
This was a single centre, single-blind, randomized, balanced, combined single dose study under fasting condition and multiple doses study under fed condition with normal diabetic-meal, two-period, two-sequence cross-over study to to compare the bioavailability of metformin hydrochloride 500 mg extended release caplet (test drug) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation).
Read the detailed description
On Day 1, to obtain pharmacokinetic profile of a single dose, the test or reference drugs were given with 200 mL of water and swallowed without chewing the drug. For multiple doses administration at Day 2 until Day 5, the study drugs were administered at a regimen of one tablet each day, 30 minutes after breakfast. Time of drug administration was standardized for all participating subjects throughout the study period.
From each subject, on Day 1 until Day 5 blood samples were drawn 5 mL before breakfast and drug administration; and breakfast was provided only on Day 2 until Day 5. Only on Day 1 and Day 5 after drug administration, the blood samples were drawn 5 mL each at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours.
The blood samples drawn on Day 1 were used to show the single dose pharmacokinetic profile under fasting condition; while those drawn on Day 5 were used to show the multiple-dose-pharmacokinetic profile after meal intake.
One week after the first drug administration (washout period), the same procedure was repeated with the alternate drug.
The plasma concentrations of metformin were determined by high performance liquid chromatography with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed in the single dose study were AUCt, AUCinf, Cmax, tmax, and t1/2. The pharmacokinetic parameters assessed in multiple doses study at steady state phase were AUCtau, Cmax, Cmin, and t1/2.
- Being tested
- 500 mg metformin hydrochloride extended release caplet (test drug), 500 mg metformin hydrochloride prolonged release tablet (reference drug)
- Keywords
- Biguanide, anti-hyperglycaemic, bioavailability, bioequivalence, metformin, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
500 mg metformin hydrochloride extended release caplet (test drug)Drug
Also called Glumin® XR, manufactured by PT Ferron Par Pharmaceuticals
In each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered.
500 mg metformin hydrochloride prolonged release tablet (reference drug)Drug
Also called Glucophage® SR, manufactured by PT Merck Pharmaceuticals
In each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered.
| Study group | Role | What they receive |
|---|---|---|
| Group I | Experimental | 500 mg metformin hydrochloride extended release caplet (PT Ferron Par Pharmaceuticals) Receives: Drug: 500 mg metformin hydrochloride extended release caplet (test drug) |
| Group II | Active comparator | 500 mg metformin hydrochloride prolonged release tablet (PT Merck Pharmaceuticals) Receives: Drug: 500 mg metformin hydrochloride prolonged release tablet (reference drug) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bioavailability
Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation) at a single dose.
Measured: 24 hours
Bioavailability
Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at multiple doses.
Measured: 5 days
Secondary outcomes (3)
Bioavailability
Relative bioavailability (secondarily measured by tmax and t1/2) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at a single dose.
Measured: 24 hours
Bioavailability
Relative bioavailability (secondarily measured by tmax and t1/2) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at multiple doses.
Measured: 5 days
Adverse events
Adverse events occurred during the study conduct (2 months) were properly and sufficiently handled and recorded.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2012 (estimated)
- Study startOct 2009
- Primary completionDec 2009
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Metformin XR BE Study in Healthy Volunteers With Single and Multiple DoseStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dexa Medica Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Danang A. Yunaidi, MD, Principal investigator, PT Equilab International
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01677260
- Sponsor's protocol ID
- PR. 143/EQL/2009
- Status last verified
- Aug 2012
- First submitted
- 29 Aug 2012
- Last updated
- 31 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Caille G, Lacasse Y, Raymond M, Landriault H, Perrotta M, Picirilli G, Thiffault J, Spenard J. Bioavailability of metformin in tablet form using a new high pressure liquid chromatography assay method. Biopharm Drug Dispos. 1993 Apr;14(3):257-63. doi: 10.1002/bdd.2510140308.
PubMed 8490112Cheng CL, Chou CH. Determination of metformin in human plasma by high-performance liquid chromatography with spectrophotometric detection. J Chromatogr B Biomed Sci Appl. 2001 Oct 5;762(1):51-8. doi: 10.1016/s0378-4347(01)00342-5.
PubMed 11589458Najib N, Idkaidek N, Beshtawi M, Bader M, Admour I, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of metformin 500 mg tablets (Dialon & Glucophage)--in healthy human volunteers. Biopharm Drug Dispos. 2002 Oct;23(7):301-6. doi: 10.1002/bdd.326.
PubMed 12355581Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 1996 May;30(5):359-71. doi: 10.2165/00003088-199630050-00003.
PubMed 8743335
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Combined Single Dose Study Under Fasting Condition And Multiple Doses Study Under Normal Diabetic Meal Comparing the Bioavailability of Two Formulations of 500 mg Metformin Hydrochloride Extended Release Tablets.
- ClinicalTrials.gov ID
- NCT01677260
- Acronym / sponsor ID
- PR. 143/EQL/2009
- Keywords
- Biguanide, anti-hyperglycaemic, bioavailability, bioequivalence, metformin, pharmacokinetics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Dexa Medica GroupIndustry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Dec 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 31 Aug 2012 (estimated)
- 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.
This was a single centre, single-blind, randomized, balanced, combined single dose study under fasting condition and multiple doses study under fed condition with normal diabetic-meal, two-period, two-sequence cross-over study to to compare the bioavailability of metformin hydrochloride 500 mg extended release caplet (test drug) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation).
Detailed description
On Day 1, to obtain pharmacokinetic profile of a single dose, the test or reference drugs were given with 200 mL of water and swallowed without chewing the drug. For multiple doses administration at Day 2 until Day 5, the study drugs were administered at a regimen of one tablet each day, 30 minutes after breakfast. Time of drug administration was standardized for all participating subjects throughout the study period.
From each subject, on Day 1 until Day 5 blood samples were drawn 5 mL before breakfast and drug administration; and breakfast was provided only on Day 2 until Day 5. Only on Day 1 and Day 5 after drug administration, the blood samples were drawn 5 mL each at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours.
The blood samples drawn on Day 1 were used to show the single dose pharmacokinetic profile under fasting condition; while those drawn on Day 5 were used to show the multiple-dose-pharmacokinetic profile after meal intake.
One week after the first drug administration (washout period), the same procedure was repeated with the alternate drug.
The plasma concentrations of metformin were determined by high performance liquid chromatography with ultraviolet detection (HPLC-UV). The pharmacokinetic parameters assessed in the single dose study were AUCt, AUCinf, Cmax, tmax, and t1/2. The pharmacokinetic parameters assessed in multiple doses study at steady state phase were AUCtau, Cmax, Cmin, and t1/2.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I | Experimental | Drug: 500 mg metformin hydrochloride extended release caplet (test drug)500 mg metformin hydrochloride extended release caplet (PT Ferron Par Pharmaceuticals) |
| Group II | Active comparator | Drug: 500 mg metformin hydrochloride prolonged release tablet (reference drug)500 mg metformin hydrochloride prolonged release tablet (PT Merck Pharmaceuticals) |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male and female subjects with absence of significant diseases or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening.
- Age of 18 - 55 years
- Preferably non-smokers or smoke less than 10 cigarettes per day
- Able to participate, communicate well with the investigators and willing to provide written informed consent to participate in the study.
- BMI 18 - 25 kg/m2
Key exclusion criteria (19 listed)
- Personal/family history of allergy or hypersensitivity or contraindication to metformin hydrochloride or other biguanides and allied drug.
- Pregnant or lactating women and women of childbearing potential without adequate contraception
- Any major illnesses in the past 90 days or clinically significant ongoing chronic medical illnesses
- Clinically significant illness within 4 weeks prior to the administration of study medication
- Presence of any clinically significant abnormal values during screening
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 |
|---|---|---|
| 500 mg metformin hydrochloride extended release caplet (test drug)Also: Glumin® XR, manufactured by PT Ferron Par PharmaceuticalsIn each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered. | Drug | Group I |
| 500 mg metformin hydrochloride prolonged release tablet (reference drug)Also: Glucophage® SR, manufactured by PT Merck PharmaceuticalsIn each of the two study periods (separated by a washout of one week) a single and multiple dose of test or reference product was administered. | Drug | Group II |
Primary outcome
Bioavailability
Time frame: 24 hours
Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation) at a single dose.
Bioavailability
Time frame: 5 days
Relative bioavailability (primarily measured by AUC and Cmax) between metformin hydrochloride 500 mg extended release caplet (test formulation) and metformin hydrochloride 500 mg prolonged release tablet (reference formulation)at multiple doses.
3 secondary outcomes
Bioavailability
Time frame: 24 hours
Bioavailability
Time frame: 5 days
Adverse events
Time frame: 2 months
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 31 Aug 2012.
- Background: PubMed 8490112Caille G, Lacasse Y, Raymond M, Landriault H, Perrotta M, Picirilli G, Thiffault J, Spenard J. Bioavailability of metformin in tablet form using a new high pressure liquid chromatography assay method. Biopharm Drug Dispos. 1993 Apr;14(3):257-63. doi: 10.1002/bdd.2510140308.
- Background: PubMed 11589458Cheng CL, Chou CH. Determination of metformin in human plasma by high-performance liquid chromatography with spectrophotometric detection. J Chromatogr B Biomed Sci Appl. 2001 Oct 5;762(1):51-8. doi: 10.1016/s0378-4347(01)00342-5.
- Background: PubMed 12355581Najib N, Idkaidek N, Beshtawi M, Bader M, Admour I, Alam SM, Zaman Q, Dham R. Bioequivalence evaluation of two brands of metformin 500 mg tablets (Dialon & Glucophage)--in healthy human volunteers. Biopharm Drug Dispos. 2002 Oct;23(7):301-6. doi: 10.1002/bdd.326.
- Background: PubMed 8743335Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 1996 May;30(5):359-71. doi: 10.2165/00003088-199630050-00003.
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.
Danang A. Yunaidi, MD principal investigator
PT Equilab International
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 500 mg metformin hydrochloride extended release caplet (test drug) and 500 mg metformin hydrochloride prolonged release tablet (reference drug) in people with Metformin XR BE Study in Healthy Volunteers With Single and Multiple Dose, run by Dexa Medica Group at 1 site in Indonesia.
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 9 inclusion and 19 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 31 Aug 2012. 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 Indonesia. 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.
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?
Bioavailability (time frame: 24 hours). 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?
On the ClinicalTrials.gov record for NCT01677260, which also lists 4 linked publications.
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 31 Aug 2012.