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Comparison of the Efficacy and Tolerability of the Addition of AVANDIA to Submaximal Doses of Metformin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00501020
First received: July 12, 2007
Last updated: September 22, 2016
Last verified: September 2016
  Purpose
This was a randomized, double-blind, double dummy, multicenter study to assess the safety, efficacy and tolerability of the addition of RSG (rosiglitazone) to sub-maximal MET (metformin) combination relative to maximal MET monotherapy in subjects with type 2 DM (diabetes mellitus). The total duration of the study was approximately 20 months. The study consisted of a two-week washout period, a four to seven-week MET titration period, and a 24-week randomized treatment phase in which subjects, stratified by prior therapy, received either RSG + MET combination therapy or MET monotherapy.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Rosiglitazone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A 24-Week Randomized, Double-blind, Double-Dummy, Multicenter Study to Compare the Efficacy of AVANDIA When Added to Submaximal Doses of Metformin and to Compare the Tolerability of the Combination to Metformin Monotherapy When Administered to Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The primary efficacy variable was HbA1c change from baseline (visit 3) after 24 weeks of treatment with either RSG+MET combination therapy or Metformin monotherapy. [ Time Frame: 24 Weeks ]

Secondary Outcome Measures:
  • Secondary efficacy variables included: the change from baseline (visit 3) at week 24 (visit) in FPG, immunoreactive insulin, HbA1c and FPG responders, Questionnaire-Tolerability of GI side-effects, and Questionnaire - Quality of Life. [ Time Frame: 24 Weeks ]

Estimated Enrollment: 750
Study Start Date: April 2001
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with a diagnosis of Type 2 DM as defined by the criteria of the American Diabetes Association.
  • Exceptions were granted to those subjects over the age of 75 on a case-by-case basis and only with the expressed permission of the study sponsor.
  • Females who were post-menopausal (i.e., >6 months without a menstrual period), surgically sterile, or using acceptable contraceptive measures (oral contraceptive, Norplant, Depo-Provera, an IUD, a diaphragm with spermicide or condoms).
  • Subjects previously treated by either diet and exercise or oral therapy. Any subjects who were receiving MET or MET plus Sulfonylurea (SU) must have been receiving no more than MET 1000mg/day for at least three months prior to study entry. Subjects must have stopped previous treatment with thiazolidinediones (TZDs) at least three months prior to screening.
  • Subjects with a Body Mass Index (BMI) >=27 kg/m2.
  • Subjects who signed the Informed Consent.
  • Subjects who received monotherapy treatment within the last three months prior to study entry or drug-naives who had HbA1c levels between 7% and 10%, inclusive. Subjects who received prior combination treatment had HbA1c of at least 6.5% to 8.5%, inclusive.
  • Subjects with FPG of <270 mg/dL at screening and visit 2, must have had a FPG >=126 mg/dL at either screening or at the MET titration period (visit 2, run-in) for entry into the treatment phase of the study.

Exclusion Criteria:

  • Females who were lactating, pregnant, or planning to become pregnant.
  • Any clinically significant abnormality identified on the chest X-ray, screening physical examination, laboratory tests, or electrocardiogram, which, in the judgment of the investigator, would preclude safe completion of the study.
  • Use of TZDs or any investigational drug for glycemic control within three months prior to study entry irregardless of the treatment regimen, or use of any other investigational agent (not related to glycemic management) within 30 days or five half-lives (whichever is longer) preceding study entry.
  • Subjects with FPG >=270 mg/dL at screening.
  • Subjects with prior history of hepatocellular reaction to or severe edema associated with troglitazone or any current TZD.
  • History of significant hypersensitivity to TZDs, biguanides, or compounds with similar chemical structures.
  • Subjects currently using insulin or who discontinued its use for glycemic control within the last three months prior to study entry.
  • History of acute or chronic metabolic acidosis.
  • Presence of clinically significant renal or hepatic disease (i.e., male subjects with serum creatinine >1.5 mg/dL; female subjects with serum creatinine >1.4 mg/dL; ALT, AST, total bilirubin, GGT, or alkaline phosphatase >2.5 times the upper limit of the reference range).
  • Anemia defined by hemoglobin concentration <11.0 g/dL for males or <10.0 g/dL for females.
  • Presence of unstable or severe angina or coronary insufficiency, or any congestive heart failure requiring pharmacologic treatment.
  • Systolic BP >170mmHg or diastolic BP >100mmHg while on anti-hypertensive treatment.
  • Recent history or suspicion of current drug abuse or alcohol abuse (defined as the consumption of more than 35 units of alcohol per week.
  • Non-compliance with study medication during MET titration period (run-in).
  • Subjects, who received or anticipated receiving radiocontrast dye during the MET titration (run-in) or the randomized treatment period of the study.
  • Subjects unwilling or unable to comply with the procedure described in the protocol.
  • Subjects who were unable to read or understand the English language were excluded from the study due to the administration of the QOL assessments.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00501020

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Rosenstock J, Goldstein BJ, Wooddell MJ, Strow LJ, Waterhouse BR, Cobitz AR Greater benefits of rosiglitazone added to submaximal dose of metformin compared to maximizing metformin dose in type 2 diabetes mellitus patients. Diabetes 2004; 53 (Suppl 2): A144 Poster presented at ADA
Weissman PW, Goldstein BJ, Campbell JC, Gould ER, Waterhouse BR, Strow LJ, Cobitz AR. Rosiglitazone plus metformin combination effects on CV risk markers suggest potential CV benefits in type 2 diabetes patients. Diabetes 2004;53(Suppl 2): A28 Oral presentation at ADA

Study Data/Documents: Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 49653/284
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 49653/284
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 49653/284
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 49653/284
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 49653/284
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 49653/284
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 49653/284
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00501020     History of Changes
Other Study ID Numbers: 49653/284 
Study First Received: July 12, 2007
Last Updated: September 22, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
Type 2 Diabetes
metformin
rosiglitazone

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Rosiglitazone
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 26, 2016