Diabetes Mellitus, Type 2
Conditions
Keywords
Metformin, Rosiglitazone, Healthy volunteers, Avandamet, Fed conditions, Bioequivalence
Brief summary
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
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.
Interventions
DRUGRosiglitazone Maleate + Metformin 2 miligrams (mg) + 500 mg
Avandamet reference product
DRUGRosiglitazone Maleate + Metformin 4 miligrams (mg) + 1000 mg
Avandamet test product
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Receiving Both Test and Reference Product Participants receiving either test product: Avandamet 4 mg + 1000 mg in Period 1; followed by reference product: Avandamet 2 mg + 500 mg in Period 2 or reference product in Period 1 and test product in Period 2 | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Participants Receiving Both Test and Reference Product |
|---|---|
| Age, Continuous | 29.77 Years STANDARD_DEVIATION 6.8 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
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.
Time frame: Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | AUC0-infinity of Metformin Hydrochloride | 10419.8 ng.h/ml | Standard Deviation 2198.2 |
| Reference Product | AUC0-infinity of Metformin Hydrochloride | 11063.7 ng.h/ml | Standard Deviation 2798.3 |
90% CI: [90.7, 99.22]
Primary
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.
Time frame: Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | AUC0-infinity of Rosiglitazone Maleate | 1776.28 ng.h/ml | Standard Deviation 519.63 |
| Reference Product | AUC0-infinity of Rosiglitazone Maleate | 1825.35 ng.h/ml | Standard Deviation 494.35 |
90% CI: [93.32, 99.72]
Primary
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.
Time frame: Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | AUC0-t of Metformin Hydrochloride | 9623.4 ng.h/ml | Standard Deviation 2175.4 |
| Reference Product | AUC0-t of Metformin Hydrochloride | 10074.4 ng.h/ml | Standard Deviation 2411.7 |
90% CI: [91.67, 100.1]
Primary
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.
Time frame: Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | AUC0-t of Rosiglitazone Maleate | 1731.22 ng per hour per ml (ng.h/ml) | Standard Deviation 510.47 |
| Reference Product | AUC0-t of Rosiglitazone Maleate | 1770.93 ng per hour per ml (ng.h/ml) | Standard Deviation 469.14 |
90% CI: [93.44, 99.83]
Primary
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.
Time frame: Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Cmax of Metformin Hydrochloride | 1623.6 ng/ml | Standard Deviation 326.5 |
| Reference Product | Cmax of Metformin Hydrochloride | 1663.9 ng/ml | Standard Deviation 370.2 |
90% CI: [93.15, 102.86]
Primary
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.
Time frame: Day 1 (day that blood collection started) and Day 2 (Period 1) and Days 8 and 9 (Period 2)
Population: Participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Cmax of Rosiglitazone Maleate | 265.45 ng/ml | Standard Deviation 44.33 |
| Reference Product | Cmax of Rosiglitazone Maleate | 270.97 ng/ml | Standard Deviation 48.32 |
90% CI: [93.25, 102.5]