An Efficacy and Safety Study of Fixed-dose Rosiglitazone/Glimepiride to Treat Chinese Type 2 Diabetes Patients

A Multi-center, Randomized, Double-blind, Parallel-group Study to Compare the Efficacy and Safety of Fixed-dose Rosiglitazone/Glimepiride Combination Therapy With Glimepiride Monotherapy for 24 Weeks in Drug Naive Subjects With Type 2 Diabetes

The purpose of this study is to demonstrate that the rosiglitazone/glimepiride fixed-dose combination tablet will safely and effectively control glycemia as first-line oral therapy in drug naïve subjects with type 2 diabetes. This 24-week study will compare the effects of treatment with rosiglitazone/glimepiride to treatment with glimepiride alone. The primary objective is to demonstrate superiority of rosiglitazone/glimepiride to glimepiride in lowering Glycosylated Hemoglobin (HbA1c).

The antihyperglycemic effect of the thiazolidinedione (TZD) class of oral antidiabetic agents is due to their ability to increase insulin sensitivity at the cellular level, which in turn improves the ability of endogenous insulin to regulate glucose utilization by the tissues. Compounds of the sulfonylurea (SU) class act to stimulate insulin production by the pancreas, overcoming insulin resistance by increasing circulating insulin levels. The mechanisms of two kind OADs may be viewed as complementary, offering the opportunity for improved efficacy and durability of effect through coadministration of a TZD and a sulfonylurea.

Successful management of type 2 diabetes mellitus (T2DM) requires aggressive glycemic control starting at the earliest stages of the disease. Rosiglitazone/glimepiride combination therapy, with complementary mechanisms of action, has the potential to provide significant benefits over monotherapy as first line therapy. Treatment with rosiglitazone/glimepiride at this early stage of diabetes is expected to provide better glycemic control and allow a greater proportion of patients to achieve target glycemic goals than oral monotherapy.

This was a multicenter, randomized, double-blinded, parallel, study to compare the effects of treatment with rosiglitazone/glimepiride combination or glimepiride in drug naïve T2 DM patients.

Inclusion Criteria:

• type 2 diabetes mellitus
• HbA1c between 7.5% and 11.0% at screening
• FPG between 7.0mmol/L and 13.3mmol/L at screening and at randomization visit
• subject was treated with diet and/or exercise alone
• QTc<450mesc or QTc<480msec for patients with bundle branch block
• Body Mass Index (BMI) >19kg/m2
• Subject has given written informed consent

Exclusion Criteria:

• Documented history of significant hypersensitivity to thiazolidinediones, sulfonylureas, or compounds with similar chemical structures
• Ongoing edema or history of edema requiring pharmacological treatment in the 12 months prior to screening
• Presence of ischemic heart disease and/or peripheral arterial disease, or NYHA grade I-IV congestive heart failure
• Taking nitrates
• Clinically significant renal or hepatic disease
• Anemia
• Severe hypertriglyceridemia (TG>=5.65mmol/L)
• Use of oral corticosteroids and Nicotinic acid
• Systolic blood pressure <170mmHg, or diastolic blood pressure > 100mmHg while on anti-hypertensive treatment
• Hyperthyroidism requiring treatment
• Diagnosed macular edema
• Women who are lactating, pregnant, or planning to become pregnant
• Presence of an active cancer or recently treated for cancer
• Drug/alcohol abuse
• Unwilling or unable to comply with the procedures described in the protocol