Bioequivalence Study of Two Formulations of 500 mg Metformin Extended Release Tablet
Information source: Dexa Medica Group
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metformin XR BE Study in Healthy Volunteers With Single and Multiple Dose
Intervention: 500 mg metformin hydrochloride extended release caplet (test drug) (Drug); 500 mg metformin hydrochloride prolonged release tablet (reference drug) (Drug)
Phase: N/A
Status: Completed
Sponsored by: Dexa Medica Group Official(s) and/or principal investigator(s): Danang A. Yunaidi, MD, Principal Investigator, Affiliation: PT Equilab International
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 (test drug) and metformin
hydrochloride 500 mg prolonged release tablet (reference formulation).
Clinical Details
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.
Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment
Primary outcome: BioavailabilityBioavailability
Secondary outcome: BioavailabilityBioavailability Adverse events
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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:
- SBP 100 - 120 mmHg
- DBP 60 - 80 mmHg
- Pulse rate 60 - 90 bpm
Exclusion Criteria:
- 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
- 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
Locations and Contacts
PT Equilab International, Jakarta 12430, Indonesia
Additional Information
Related publications: Caillé G, Lacasse Y, Raymond M, Landriault H, Perrotta M, Picirilli G, Thiffault J, Spénard 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. Cheng 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. Najib 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. Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 1996 May;30(5):359-71. Review.
Starting date: October 2009
Last updated: August 30, 2012
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