Rosiglitazone-Metformin Combination Versus Metformin-Sulfonylurea Combination On Beta-Cell Function In Type 2 Diabetes - Full Text View

Sponsored by:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00367055

Purpose

It has been shown in previous study that progressive glycemic deterioration was associated with progressive loss of b-cell function, measured by the decrease in plasma insulin levels, irrespective of the therapy used (diet, sulfonylureas or metformin).There is growing evidence that thiazolidinediones could have a positive action on the b-cell function. But it has not yet been demonstrated that they could protect from a deterioration in insulin secretion in the long term. So, it appears interesting to study the long term evolution of the b-cell function and the possible protection with rosiglitazone in patients with type 2 diabetes showing evidence of loss of b-cell function with metformin alone.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: rosiglitazone-metformin Drug: Metformin Drug: metformin+ gliclazide	Phase IV

MedlinePlus related topics: Diabetes

Drug Information available for: Metformin Metformin hydrochloride Rosiglitazone Rosiglitazone Maleate Avandamet Gliclazide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Comparison of the Action of the Rosiglitazone-Metformin Fixed-Dose Combination and of a Metformin-Sulfonylurea Free Combination on the b-Cell Function in Type 2 Diabetic Patients Not Controlled With Metformin Alone.

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Beta-cell function is reflected by insulin response. Evolution of insulin secretion capacity will be assessed over 3 years, by using clamp tests and meal tests before treatment and after 18 and 36 months of treatment
Evolution of insulin secretion capacity over 3 years measured by using clamp tests and meal tests before treatment and after 18 and 36 months of treatment (or in case of early withdrawal).
1st phase insulin secretion (during the 10 first minutes) : AUC, incremental AUC and peak value
2nd phase insulin secretion (AUC from 120 to 180 minutes and incremental AUC)
Insulin sensitivity : M/I (M = Metabolized glucose, I = Insulin) from 120 to 180 minutes
(The ratio M/I is a measure of the quantity of glucose metabolized per unit of plasma insulin concentration and is thus a reasonable index of tissue sensitivity to insulin).
Arginin test (peak value, AUC and incremental AUC) from 180 to 210 minutes.
Meal test (Sustacal): peak value of insulin and AUC over 3 hours.

Secondary Outcome Measures:

insulin secretion and sensitivity at baseline,M18 and 36. HbA1c ( glycosylated haemoglobin) at baseline ,M18 and 36. C peptide at baseline, M18 and 36
HOMA: % insulin secretion and sensitivity, performed before each stimulatory test
Centralised HbA1c, C-peptide at 0, 18 and 36 months or in case of early withdrawal.
Even if clinical efficacy is not the objective of the study, the following parameters, which are essential to evaluate glycaemic control of the patients and safety
(hypoglycemia+++) to adapt the treatment over the 3 year period, will be studied as a reference for the main evaluation and an evidence of compliance and/or of a possible therapeutic failure :
Local FPG, HbA1c every 3 months (except when clamp test) and in case of early withdrawal Adverse events every 3 months and in case of early withdrawal.

Estimated Enrollment:	80
Study Start Date:	October 2004
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Eligibility

Ages Eligible for Study:	40 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

Males and females 40 to 75 years of age (inclusive at the time of screening)
Type 2 diabetes mellitus as defined by the WHO criteria, diagnosed for at least 1 year
Subjects receiving 1.5 to 3g of metformin alone at a constant dose for at least 8 weeks prior to visit 1
Patients with 6.5% < HbA1c > 8% at visit 1 and visit 2
25 < BMI < 35

EXCLUSION CRITERIA:

Patient with type 1 diabetes
Treatment with other hypoglycaemic agents than metformin in the last 3 months
FPG >200 mg/dL at visit 2
Hypersensitivity to the studied treatments (rosiglitazone, metformin chlorhydrate, gliclazide)
Congestive heart failure (NYHA class I to IV), unstable or severe angina, recent myocardial infarction
Respiratory insufficiency
Subjects who have required the use of insulin for glycaemic control in the past 6 months prior to visit 1 (except during pregnancy or acute episodes such as hospitalization, trauma or infection) or subjects with a history of metabolic acidosis including diabetic ketoacidosis
Anemia defined by haemoglobin concentration <11.0 g/dL for males and <10.0 g/dL for females
Renal disease or renal dysfunction, e.g. as suggested by serum creatinine levels ≥135.0 µmol/L in males and ≥110.0 µmol/L in females and/or creatinine clearance <40 mL/min
Presence of clinically significant hepatic disease, with ALT, AST, total bilirubin, alkaline phosphatase >2.5 times the upper limit of the normal reference range
Subjects with chronic diseases requiring periodic ot intermittent treatment with oral or IV corticosteroids
Subjects receiving danazol, miconazole or phenylbutazone
Active alcohol, drug or medication abuse within the last 6 months or any condition that would indicate the likelihood of poor subject compliance
Women who are lactating, pregnant or planning to become pregnant
Any clinically significant abnormality identified at screening which, in the investigator's judgement, makes the subject unsuitable for inclusion in the study
Use of any other investigational agent within 30 days or 5 half-lives (whichever is longer) prior to visit 1
Subjects who receive or anticipate receiving radiocontrast dye during the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00367055

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials, MD

GlaxoSmithKline

More Information

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	101765, AVAF4001
Study First Received:	August 21, 2006
Last Updated:	October 27, 2008
ClinicalTrials.gov Identifier:	NCT00367055
Health Authority:	France: National Consultative Ethics Committee for Health and Life Sciences

Keywords provided by GlaxoSmithKline:

Beta cell function
Type 2 diabetes
Combination treatment

Study placed in the following topic categories:

Metabolic Diseases
Gliclazide
Metformin
Diabetes Mellitus, Type 2
Diabetes Mellitus

Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Rosiglitazone

Additional relevant MeSH terms:

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009