GXR RM 500 mg Korea BE Study
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/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:
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:
|
| 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:
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:
|
| 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:
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:
|
| 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:
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:
|
Outcome Measures
Primary Outcome Measures
- 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]
- Maximum Observed Plasma Concentration (Cmax) of Metformin [Pre-dose up to 32 hours post-dose]
Secondary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [Day 1 up to Day 21]
- Number of Participants Taking Concomitant Medications [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 (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.
- Area Under Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Metformin [Pre-dose up to 32 hours post-dose]
- 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]
- Apparent Terminal Half-life (t½) of Metformin [Pre-dose up to 32 hours post-dose]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metformin [Pre-dose up to 32 hours post-dose]
Eligibility Criteria
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
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Have no history of gastrointestinal resection that may affect drug absorption
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Have no history of psychiatric disorder within 5 years prior to screening
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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
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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)
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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)
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Other protocol defined inclusion criteria could apply
Exclusion Criteria:
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Participants determined ineligible to participate in this study at the discretion of the Principal Investigator (or delegated investigators)
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Hypersensitivity to venous puncture
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Known hypersensitivity to ingredients of Study Interventions or Biguanides, or having other clinically relevant hypersensitivities
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Type I diabetes mellitus, lactic acidosis, acute or chronic metabolic acidosis including diabetic ketoacidosis, with or without coma; diabetic pre-coma, pre-diabetes
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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
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Participants with severe infection or severe traumatic general disorder
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Participants who are scheduled to undergo surgical procedures
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Participants with malnutrition, inanition, pituitary dysfunction or adrenal function failure
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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.
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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.)
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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
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Use of any medication that may affect the outcome of the study within 10 days prior to screening and during study conduct
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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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Trials Center, Chungnam National University Hospital | Daejeon | Korea, Republic of | 35015 |
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.- MS200084_0028