Avandamet Bioequivalence Study Brazil - Fed Administration

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.

• Rosiglitazone Maleate + Metformin 2 miligrams (mg) + 500 mg (Drug): Avandamet reference product
• Rosiglitazone Maleate + Metformin 4 miligrams (mg) + 1000 mg (Drug): Avandamet test product

Primary outcomes

• AUC0-t of Rosiglitazone Maleate [Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)]: 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.
• Cmax of Rosiglitazone Maleate [Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)]: 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.
• AUC0-infinity of Rosiglitazone Maleate [Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)]: 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.
• AUC0-t of Metformin Hydrochloride [Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)]: 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.
• AUC0-infinity of Metformin Hydrochloride [Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)]: 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.
• Cmax of Metformin Hydrochloride [Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)]: 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.

Sex: All, ages: 18 Years to 50 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• AUC0-t of Rosiglitazone Maleate (Primary), Mean, ng per hour per ml (ng.h/ml): Test Product 1731.22 +/- 510.47; Reference Product 1770.93 +/- 469.14
• Cmax of Rosiglitazone Maleate (Primary), Mean, ng/ml: Test Product 265.45 +/- 44.33; Reference Product 270.97 +/- 48.32
• AUC0-infinity of Rosiglitazone Maleate (Primary), Mean, ng.h/ml: Test Product 1776.28 +/- 519.63; Reference Product 1825.35 +/- 494.35
• AUC0-t of Metformin Hydrochloride (Primary), Mean, ng.h/ml: Test Product 9623.4 +/- 2175.4; Reference Product 10074.4 +/- 2411.7
• AUC0-infinity of Metformin Hydrochloride (Primary), Mean, ng.h/ml: Test Product 10419.8 +/- 2198.2; Reference Product 11063.7 +/- 2798.3
• Cmax of Metformin Hydrochloride (Primary), Mean, ng/ml: Test Product 1623.6 +/- 326.5; Reference Product 1663.9 +/- 370.2

Adverse events

Other adverse events by term

• GSK Clinical Trials, Study director, GlaxoSmithKline