Metformin ER 750 mg Tablets, Fasting

Study Overview
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Brief Summary
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The objective of this study is to compare the rate and extent of absorption of metformin from a test formulation of Metformin ER 750 mg Tablets versus the reference Glucophage® XR 750 mg Tablets under fasting conditions.

Detailed Description
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Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods

Official Title
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A Two-Way Crossover, Open-Label, Single-Dose, Fasting, Bioequivalence Study of Metformin ER 750 mg Tablets Versus Glucophage® XR 750 mg Tablets in Normal Healthy Non-smoking Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Glucophage® XR 750 mg Tablets
* Drug: Metformin ER 750 mg Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking male or female with a minimum age of 18 years (i.e. non-smoker or non-tobacco user for at least 90 days prior to pre-study medical screening). Body Mass Index (BMI - weight/height²) greater than or equal to 19 kg/m² and less than or equal to 30 kg/m². Availability of subject for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed Informed Consent Form. Normal findings in the physical examination, 12-lead ECG and vital signs (blood pressure between 100-140/60-90 mmHg, heart rate between 50-99 beats/min, temperature between 35.8ºC and 37.5ºC). Negative for drugs of abuse, nicotine, alcohol, hepatitis B-surface antigen, hepatitis C and HIV, and for female subjects, pregnancy (serum ß-CG). No clinical laboratory values outside of the acceptable range as defined by BCR, unless the Principal Investigator decides they are not clinically significant. Female subjects who are surgically sterile for at least six months or post-menopausal for at least one year, or who will avoid pregnancy prior to the study, during the study and up until one month after the end of the study. Exclusion Criteria: Known history of hypersensitivity to metformin (e.g. Glucophage®) and/or related drugs such as glyburide (Diaβeta®, Euglucon®), tolbutamide (Orinase®, Apo-chlorpropamide), acetohexamide (Dimelor®), chlorpropamide (Diabinese®) and glipizide (Glucotrol®, Glibenese®). Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurologic, hematological, liver, or kidney disease unless judged no clinically significant by the Principal Investigator, or medical designate. Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. Any clinically significant illness during the last four weeks prior to entry into this study. Presence of any significant physical or organ abnormality. Any subject with a history of drug abuse. Any psychiatric or psychological disease (including depression) unless deemed not clinically significant by the Principal Investigator, or medical designate. Use of any prescription medication within 14 days preceding entry into this study. Use of over-the-counter (OTC) medication within seven days preceding entry into this study (except for spermicidal/barrier contraceptive products). Female subjects: use of oral contraceptives or contraceptive implants (Such as Norplant®) within 30 days prior to drug administration or a depot injection of progestogen drug (e.g. Depro-Provera®) within one year prior to drug administration. Female subjects: presence of pregnancy or lactation. Any subject who has had blood withdrawn within 56 days preceding this study, taken during the conduct of any clinical study at a facility other than BCR, or within the lockout period specified by a previous study conducted at BCR. Participation in a clinical trial with an investigational drug within 30 days preceding this study. Any subject who has donated blood within 56 days preceding this study. Any subject who has participated as a plasma donor in a plasmapheresis program within seven days preceding this study. Significant or recent history of asthma (After 12 years of age). Any subject with a recent (less than one year) history of alcohol abuse. Intolerance to venipuncture.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Metformin ER 750 mg Tablets<br>* 1 x 750 mg, single-dose fasting<br>|
| Active Comparator: 2<br> | Drug: Glucophage® XR 750 mg Tablets<br>* 1 x 750 mg, single-dose fasting<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | Bioequivalence based on Cmax. | Blood samples collected over a 36 hour period. | 
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Bioequivalence based on AUC0-t. | Blood samples collected over a 36 hour period. | 
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | Bioequivalence based on AUC0-inf. | Blood samples collected over a 36 hour period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Healthy Subjects