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

NCT00367055 | Completed Phase 4 Results

• 2 other identifiers: 101765AVAF4001
• Study Type: interventional
• Target: 84
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Beta cell function; Type 2 diabetes; Combination treatment

Outcome Measures

Primary Outcomes (1)

• Median Change From Baseline in the Insulin Secretory Capacity After a 36-month Treatment

  Change from baseline in the insulin secretory capacity was measured by the assesment of blood insulin concentrations (conc.) using the hyperglycaemic clamp (HC) technique, per intravenous glucose perfusion by a catheter. Change from baseline for insulin conc peaks (highest conc level) was calculated as the Month 36 value minus the baseline value. Insulin secretion was assessed by calculating AUC during the first 10 minutes of HC (incremental and total AUC0-10 min) and the AUC after the first 10 minutes of the HC (10-180min).

  Baseline and Month 36

Secondary Outcomes (9)

• Median Change From Baseline in the Ratio M/I After a 36-month Treatment

  Baseline and Month 36

• Median Change From Baseline in the Insulin Secretion Capacity After an 18-month Treatment

  Baseline and Month 18

• Mean Change From Baseline in HbA1c at Month 36

  Baseline and Month 36

• Mean Change From Baseline in FBG at Month 36

  Baseline and Month 36

• Median Change From Baseline in Insulin Resistance Index (HOMA-IR) After a 36-month Treatment

  Baseline and Month 36

Interventions

rosiglitazone-metformin DRUG

Metformin DRUG

metformin+ gliclazide DRUG

Also known as: rosiglitazone-metformin, Metformin

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• \< BMI \< 35

You may not qualify if:

• 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
• Use of any other investigational agent within 30 days or 5 half-lives (whichever is longer) prior to visit 1

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

rosiglitazone-metformin combination; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials, MD

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 21, 2006
• First Posted: August 22, 2006
• Study Start: October 1, 2004
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: July 27, 2010
• Results First Posted: November 5, 2009

Record last verified: 2010-07