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

GlaxoSmithKline0 sites750 target enrollmentJune 5, 2001

ConditionsDiabetes Mellitus, Type 2

DrugsRosiglitazone

Overview

Phase: Phase 4
Intervention: Not specified
Conditions: Diabetes Mellitus, Type 2
Sponsor: GlaxoSmithKline
Enrollment: 750
Primary Endpoint: 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.
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

June 5, 2001

End Date

February 13, 2003

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility 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/m
•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.

Outcomes

Primary Outcomes

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 Outcomes

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.(24 Weeks)