GXR RM (Glucophage® Extended Release Reduced Mass) 500 Milligram (mg) Korea Bioequivalence (BE) Study
Condition: Healthy
Intervention: Glucophage® XR RM Test; Glucophage® XR Reference
Intervention description: Participants received a single oral dose of 500 mg of test Glucophage® XR RM tablet under fasting or fed conditions.; Participants received a single oral dose of 500 mg of reference Glucophage® XR tablet under fasting or fed conditions.
Intervention MeSH terms: Metformin
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: All
Minimum age: 19 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Diabetes Mellitus; Glucophage Extended Release; Bioequivalence Study

Summary:

      The purpose of this study was to assess bioequivalence (BE) of newly developed Glucophage® XR
      (GXR) reduced mass (RM) tablet (metformin hydrochloride 500 milligrams (mg) test tablet) and
      marketed Glucophage ® XR tablet (metformin hydrochloride 500 mg reference tablet) following
      single oral dose administration under fasted and fed conditions by comparing
      pharmacokinetics, safety and tolerability between test and reference in healthy participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All values for hematology and biochemistry tests of blood and urinalysis (especially
             Estimated Glomerular Filtration Rate [eGFR] greater than [>] 80 milliliters per minute
             per 1.73 square meter [80 ml/min/1.73 m^2] and normal Creatinine) within the normal
             range or showing no clinically relevant deviation as judged by the Investigator

          -  Are not having congenital or chronic diseases, nor pathological symptoms based on the
             screening

          -  Have no history of gastrointestinal resection that may affect drug absorption

          -  Have no history of psychiatric disorder within 5 years prior to screening

          -  Vital signs (body temperature [tympanic], blood pressure [BP], and pulse rate in
             sitting position) within the normal range or showing no clinically relevant deviation
             as judged by the Investigator

          -  Electrocardiogram recording (12-lead) without signs of clinically relevant pathology
             in particular QTc (Bazett) less than or equal to [<=] 450 millisecond (ms)

          -  Non-smoker (that is [i.e.] zero cigarettes, pipes, cigars or others) at least three
             months before study entry

          -  Negative screen for Hepatitis B surface antigen (HBsAg) and Hepatitis B Virus antibody
             (anti-HBc), Hepatitis C Virus antibody (anti-HCV) and Human Immunodeficiency Virus
             antibodies (anti-HIV 1 and 2) and Rapid Plasma Reagin Antibody (RPR Ab)

          -  Have a body weight within the range 55 to 95 kilograms (kg) and a Body Mass Index
             (BMI) within the range 18.5 to 29.9 kilograms per square meter (kg/m^2) (inclusive)

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Participants determined ineligible to participate in this study at the discretion of
             the Principal Investigator (or delegated investigators)

          -  Hypersensitivity to venous puncture

          -  Known hypersensitivity to ingredients of Study Interventions or Biguanides, or having
             other clinically relevant hypersensitivities

          -  Type I diabetes mellitus, lactic acidosis, acute or chronic metabolic acidosis
             including diabetic ketoacidosis, with or without coma; diabetic pre-coma, pre-diabetes

          -  Participants with renal impairment (eGFR < 80 ml/min/1.73m^2) - calculations according
             to Modification of Diet in Renal Disease (MDRD) formula). Participants presenting with
             acute conditions with the potential to alter renal function such as dehydration,
             severe infection, cardiovascular collapse (shock), acute myocardial infraction, and
             septicemia

          -  Participants with acute and unstable heart failure

          -  Participants with severe infection or severe traumatic general disorder

          -  Participants who are scheduled to undergo surgical procedures

          -  Participants with malnutrition, inanition, pituitary dysfunction or adrenal function
             failure

          -  Participants with hepatic dysfunction, acute or chronic disease which may cause tissue
             hypoxia such as respiratory failure, acute myocardial infarction, shock and
             gastrointestinal (GI) disorder such as excessive alcohol intake, hydration, diarrhea,
             vomiting etc.

          -  Participants undergoing intravascular administration of iodinated contrast materials
             in radio diagnostic examinations (for example, intravenous urogram, intravenous
             cholangiography, angiography, and computed tomography (CT) scans with intravascular
             contrast materials etc.)

          -  Participants who took drugs that significantly induce (e.g., barbiturate) or inhibit
             drug metabolism enzymes, and those drugs that may alter metformin pharmacokinetic
             (pK), most importantly organic cation transporter 1/2 [OCT1/2] inhibitors and
             inducers, within 30 days prior to screening

          -  Use of a concomitant drug. However, any medications that are considered necessary for
             participant's welfare and will not interfere with the trial medication may be given at
             the discretion of the investigator

          -  Use of any medication that may affect the outcome of the study within 10 days prior to
             screening and during study conduct

          -  Participation in another bioequivalence or other clinical studies where the last
             administration of previous study medication was within 6 months, before the first drug
             administration in this study

          -  Other protocol defined exclusion criteria could apply