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:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00501020
First received: July 12, 2007
Last updated: October 1, 2010
Last verified: October 2010
  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
Type 2 Diabetes
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
Study Completion Date: February 2003
Primary Completion Date: February 2003 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00501020

  Show 71 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, M.D., Ph.D. GlaxoSmithKline
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00501020     History of Changes
Other Study ID Numbers: 49653/284
Study First Received: July 12, 2007
Last Updated: October 1, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Type 2 Diabetes
rosiglitazone
metformin

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

ClinicalTrials.gov processed this record on October 19, 2014