Bioequivalence Study of Two Formulations of 500 mg Metformin Extended Release Tablet
Condition: Metformin XR BE Study in Healthy Volunteers With Single and Multiple Dose
Study type: Interventional

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).
    

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.
    

Intervention name(s): 500 mg metformin hydrochloride extended release caplet (test drug); 500 mg metformin hydrochloride prolonged release tablet (reference drug)
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Glumin® XR, manufactured by PT Ferron Par Pharmaceuticals; Glucophage® SR, manufactured by PT Merck Pharmaceuticals
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Biguanide; anti-hyperglycaemic; bioavailability; bioequivalence; metformin; pharmacokinetics