GXR RM 500 mg Korea BE Study

Sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04684420
Collaborator
(none)
82
Enrollment
1
Location
4
Arms
12.1
Anticipated Duration (Months)
6.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is 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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: Glucophage® XR Test
  • Drug: Glucophage® XR Reference
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
82 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Randomized Phase I, Open-Label, Active-Controlled Study Assessing The BE Between Single Doses of 500 mg GXR RM Tablets and 500 mg GXR Tablets Under Fasted and Fed State in Two 2-Way Crossover Groups of Healthy Participants
Actual Study Start Date :
Dec 22, 2020
Anticipated Primary Completion Date :
Dec 24, 2021
Anticipated Study Completion Date :
Dec 24, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: First Test GXR (Fasting), Then Reference GXR (Fasting)

Participants will receive a single oral dose of 500 milligrams (mg) of test GXR tablet on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR tablet on Day 8 in treatment period 2 under fasting conditions. There will be separate washout period of 7 days between each treatment period.

Drug: Glucophage® XR Test
Participants will receive a single oral dose of 500 mg of test Glucophage® XR tablet under fasting or fed conditions.
Other Names:
  • Metformin hydrochloride
  • Drug: Glucophage® XR Reference
    Participants will receive a single oral dose of 500 mg of reference Glucophage® XR tablet under fasting or fed conditions.
    Other Names:
  • Metformin hydrochloride
  • Experimental: First Reference GXR (Fasting), Then Test GXR (Fasting)

    Participants will receive a single oral dose of 500 mg of reference GXR tablet on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR tablet on Day 8 in treatment period 2 under fasting conditions. There will be separate washout period of 7 days between each treatment period.

    Drug: Glucophage® XR Test
    Participants will receive a single oral dose of 500 mg of test Glucophage® XR tablet under fasting or fed conditions.
    Other Names:
  • Metformin hydrochloride
  • Drug: Glucophage® XR Reference
    Participants will receive a single oral dose of 500 mg of reference Glucophage® XR tablet under fasting or fed conditions.
    Other Names:
  • Metformin hydrochloride
  • Experimental: First Test GXR (Fed), Then Reference GXR (Fed)

    Participants will receive a single oral dose of 500 mg of test GXR tablet on Day 1 in treatment period 1 followed by a single oral dose of 500 mg reference GXR tablet on Day 8 in treatment period 2 under fed conditions. There will be separate washout period of 7 days between each treatment period.

    Drug: Glucophage® XR Test
    Participants will receive a single oral dose of 500 mg of test Glucophage® XR tablet under fasting or fed conditions.
    Other Names:
  • Metformin hydrochloride
  • Drug: Glucophage® XR Reference
    Participants will receive a single oral dose of 500 mg of reference Glucophage® XR tablet under fasting or fed conditions.
    Other Names:
  • Metformin hydrochloride
  • Experimental: First Reference GXR (Fed), Then Test GXR (Fed)

    Participants will receive a single oral dose of 500 mg of reference GXR tablet on Day 1 in treatment period 1 followed by a single oral dose of 500 mg test GXR tablet on Day 8 in treatment period 2 under fed conditions. There will be separate washout period of 7 days between each treatment period.

    Drug: Glucophage® XR Test
    Participants will receive a single oral dose of 500 mg of test Glucophage® XR tablet under fasting or fed conditions.
    Other Names:
  • Metformin hydrochloride
  • Drug: Glucophage® XR Reference
    Participants will receive a single oral dose of 500 mg of reference Glucophage® XR tablet under fasting or fed conditions.
    Other Names:
  • Metformin hydrochloride
  • Outcome Measures

    Primary Outcome Measures

    1. Area Under the Plasma Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of Metformin [Pre-dose up to 32 hours post-dose]

    2. Maximum Observed Plasma Concentration (Cmax) of Metformin [Pre-dose up to 32 hours post-dose]

    Secondary Outcome Measures

    1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [Day 1 up to Day 21]

    2. Number of Participants Taking Concomitant Medications [Day 1 up to Day 21]

    3. Number of Participants With Clinically Significant Change from Baseline in Vital Signs, Laboratory Parameters, Physical Examination Findings and 12-Lead Electrocardiogram (ECG) Findings [Day 1 up to Day 21]

      Number of participants with clinically significant change from baseline in vital signs, laboratory parameters, physical examination findings and 12-lead electrocardiogram findings will be reported.

    4. Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin [Pre-dose up to 32 hours post-dose]

    5. Ratio of Area Under the Plasma Concentration-Time Curve from Time Zero to the Last Sampling Time (AUC0-tlast) to Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin [Pre-dose up to 32 hours post-dose]

    6. Apparent Terminal Half-life (t½) of Metformin [Pre-dose up to 32 hours post-dose]

    7. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin [Pre-dose up to 32 hours post-dose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Clinical Trials Center, Chungnam National University HospitalDaejeonKorea, Republic of35015

    Sponsors and Collaborators

    • Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

    Investigators

    • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    ClinicalTrials.gov Identifier:
    NCT04684420
    Other Study ID Numbers:
    • MS200084_0028
    First Posted:
    Dec 24, 2020
    Last Update Posted:
    Nov 18, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 18, 2021