Glucophage Extended Release (GXR) China Bioequivalence Study (Nantong - Darmstadt)
Condition: Healthy
Intervention: Test GXR; Reference GXR
Intervention description: Participants received a single oral dose of 500 mg of test GXR tablet (Merck Nantong/China) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).; Participants received a single oral dose of 500 mg of reference GXR tablet (Merck Darmstadt/France) under fasting or fed conditions on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Intervention MeSH terms: Metformin
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Diabetes Mellitus; Glucophage Extended Release (GXR); Bioequivalence Study

Summary:

      The study will assess the bioequivalence between single doses of GXR manufactured in Merck
      Nantong China (test drug) and GXR manufactured in Merck Darmstadt Germany (reference drug)
      under fed and fasted state in healthy participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Overtly healthy as determined by medical evaluation, including medical history and a
             physical examination

          -  Have a body weight within 50 to 90 kilogram (kg) and Body mass index (BMI) within the
             range 18 to 30 kg per meter square (kg/m^2) (inclusive)

          -  Chinese male and female (at least 1/4 of each gender per study group)

          -  A male participant must agree to use and to have their female partners use a highly
             effective contraception (that is, methods with a failure rate of less than 1 percent
             per year) for a period of at least 1 month before and after dosing

          -  A female is eligible if she is not pregnant (that is, after a confirmed menstrual
             period and a negative serum pregnancy test), not breastfeeding, and at least one of
             the following conditions applies

          -  Is not a woman of childbearing potential (WOCBP) OR

          -  Is a WOCBP who agrees to use a highly effective contraceptive method (that is, has a
             failure rate of less than 1 percent per year) for a period of at least 1 month before
             and after dosing

          -  Can give signed informed consent, which includes compliance with the requirements and
             restrictions listed in the informed consent form (ICF) and this protocol

          -  Non-smoker (0 cigarettes, pipes, cigars, or others) since at least 3 months

          -  All values for biochemistry and hematology tests of blood and urine within the normal
             range or showing no clinically relevant deviation as judged by the Investigator

          -  Electrocardiogram recording (12 lead ECG) without signs of clinically relevant
             pathology as judged by the Investigator.

          -  Pulse, body temperature, and respiration in sitting position within the normal range
             or showing no clinically relevant deviation as judged by the Investigator. Blood
             pressure in sitting position within normal range: greater than or equals to (>=) 90
             millimeter of mercury (mmHg) and less than or equal to (=<) 139 mmHg for systolic
             blood pressure; >= 60 mmHg and =< 90 mmHg for diastolic blood pressure

          -  Negative screen for alcohol and drugs of abuse (cannabis, benzodiazepines,
             barbiturates, opiates, cocaine, and methyl amphetamine) at screening and on admission

          -  Negative screen for hepatitis A virus (HAV) antibodies, hepatitis B surface antigen
             (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV)
             antibodies, and Treponema pallidum (TP) antibodies

        Exclusion Criteria:

          -  Participation in a clinical trial within 90 days prior to first drug administration

          -  Blood donation (equal or more than 500 milliliter [mL]) or significant blood loss
             within 90 days prior to first drug administration

          -  Any surgical or medical condition, including findings in the medical history or in the
             pre-study assessments, or any other significant disease, that in the opinion of the
             Investigator, constitutes a risk or a contraindication for the participation of the
             participant in the study or that could interfere with the study objectives, conduct or
             evaluation

          -  History of surgery of the gastrointestinal tract which could influence the
             gastrointestinal absorption and/or motility according to the Investigator's opinion

          -  History or presence of relevant liver diseases or hepatic dysfunction.

          -  Allergy: ascertained or presumptive hypersensitivity to the active drug substance
             and/or formulations' ingredients; history of anaphylaxis to drugs or allergic
             reactions in general, which the Investigator considers may affect the outcome of the
             study

          -  Receipt of any prescription or non-prescription medication within 2 weeks before the
             first Investigational medicinal product (IMP) administration, including multivitamins
             and herbal products (that is St John's Wort, or traditional Chinese medicines), except
             for the permitted medications

          -  Renal failure or renal dysfunction (creatinine clearance [Ccr] < 80 mL/minute) as
             assessed by using the estimated measure with the Cockcroft-Gault equation.

          -  Known lack of participant compliance or inability to communicate or cooperate with the
             Investigator (example, language problem, poor mental status)

          -  Non-acceptance of study high-fat breakfast (example, vegetarians, vegans and
             participants who follow special diets)

          -  Consumption of large quantities of methylxanthine-containing beverages (>5 cups of
             coffee/day or equivalent)

          -  Consumption of grapefruit, cranberry, or juices of these fruits, from 14 days prior to
             drug administration until collection of the last Pharmacokinetics sample in Period 2

          -  Any contraindication to Glucophage

          -  Abnormal and clinically significant chest X-ray finding at screening