Avandamet Bioequivalence Study Brazil - Fed Administration

Study Overview
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Brief Summary
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The study is prospective, open-label, randomized, crossover, with 02 treatments, 02 sequences, and 02 periods. The volunteers received, in each period, the reference or the test formulation after standardized meals.

Detailed Description
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This is an open-label, randomized, crossover study with 02 treatments, 02 sequences, and 02 periods, in which the healthy volunteers received, in each period, the test or the reference formulation after standardized meals. Test product is Rosiglitazone Maleate + Metformin - Avandamet 4 mg + 1000 mg (GlaxoSmithKline Brasil Ltda) in the form of film coated tablets. Reference product is Rosiglitazone Maleate + Metformin - Avandamet 2 mg + 500 mg (Glaxo Smith Kline Brasil Ltda) in the form of film coated tablets. The population is composed by 26 healthy volunteers, adults, of both genders and their ages varied between 18 and 50 years. Their body mass index (BMI) varied between 18,5 and 25. There are no restrictions regarding the ethnic group. The relative bioavailability of the two formulations, after oral administration, will be evaluated based on statistical comparisons of relevant pharmacokinetic parameters obtained from data of drug concentration in blood.

Official Title
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Assessment of Relative Bioavailability of Avandamet 4 mg + 1000 mg (GSK) in the Form of Film Coated Tablets Versus Avandamet 2 mg + 500 mg (GSK) in the Form of Film Coated Tablets, in Healthy Volunteers After Feeding Standardized, Using Liquid Chromatography.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Rosiglitazone Maleate + Metformin 2 miligrams (mg) + 500 mg
* Drug: Rosiglitazone Maleate + Metformin 4 miligrams (mg) + 1000 mg


Participation Criteria
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Eligibility Criteria
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EXCLUSION CRITERIA: The volunteer has a known hypersensitivity to the study drug or to compounds chemically related; History or presence of hepatic or gastrointestinal illnesses, or other condition that interferes over the drug's absorption, distribution, excretion or metabolism; History of neurological, endocrine, pulmonary, hamatologic, immune, brain, metabolic or cardiovascular illness; Hypo or hypertension of any etiologic that needs pharmacologic treatment; The results of the laboratory exams are out of the values considered as normal according this protocol's rules, unless that they are considered as clinically irrelevant by the investigator; Has history of alcohol or drugs abuse; History of use drug inducing and/or inhibitors of hepatic metabolism within 30 days prior to drug study administration; Use of MAO inhibitors two weeks before the start of treatment; - Use of inhibitors of 5-TH reuptake, Pregnancy or breastfeeding, Smoking; Use of regular medication within 4 weeks prior to study iniciation; Use of experimental drug or participation in any clinical study within 6 months prior to study iniciation. INCLUSION CRITERIA: Age between 18 and 50 years; Body mass index ≥ 18,5 and ≤25,0, can vary up to 15% for the upper limit (18,5 to 28,75); Good health conditions; Obtain the Informed Consent's signed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Avandamet test product<br>Test product: Avandamet (Rosiglitazone Maleate + Metformin) 4 miligrams (mg) + 1000 mg in Period 1, followed by a 7-day washout period during which no medication was administered, followed by reference product: Avandamet (Rosiglitazone Maleate + Metformin) 2 mg + 500 mg in Period 2 | Drug: Rosiglitazone Maleate + Metformin 4 miligrams (mg) + 1000 mg<br>* Avandamet test product<br>|
| Active Comparator: Avandamet reference product<br>Reference product: Avandamet (Rosiglitazone Maleate + Metformin) 2 miligrams (mg) + 500 mg in Period 1; followed by a 7-day washout period during which no medication was administered; followed by test product: Avandamet (Rosiglitazone Maleate + Metformin) 4 mg + 1000 mg in Period 2 | Drug: Rosiglitazone Maleate + Metformin 2 miligrams (mg) + 500 mg<br>* Avandamet reference product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t of Rosiglitazone Maleate | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC 0-t is calculated from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; ml, milliliter. | Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2) | 
| Cmax of Rosiglitazone Maleate | Cmax is defined as the maximum or peak concentration of a drug observed after its administration. Cmax is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. | Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2) | 
| AUC0-infinity of Rosiglitazone Maleate | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. | Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2) | 
| AUC0-t of Metformin Hydrochloride | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-t is calculated from time 0 (prior to administration of medication) to time t (the time of the last quantifiable concentration). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. ng, nanograms; ml, milliliter. | Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2) | 
| AUC0-infinity of Metformin Hydrochloride | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. | Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2) | 
| Cmax of Metformin Hydrochloride | Cmax is defined as the maximum or peak concentration of a drug observed after its administration. Cmax is one of the parameters of particular use in estimating the bioavailability of drugs, by measuring the total amount of drug absorbed. | Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Rosiglitazone, Healthy volunteers, Avandamet, Fed conditions, Bioequivalence