The safety and efficacy of BRENZAVVY were evaluated in 23 clinical studies. Highlighted below are some of the key Phase 3 studies.
Safety and Effectiveness Compared to Dapagliflozin as an Adjunct to Metformin for Treatment of Type 2 Diabetes Mellitus in Adults
A phase 3, randomized, double-blind, active-controlled trial compared the safety and effectiveness of BRENZAVVY, 20 mg, to dapagliflozin, 10 mg, as an adjunct to metformin for the treatment of type 2 diabetes mellitus in adults. The study population consisted of 406 participants who received BRENZAVVY or dapagliflozin in addition to ongoing metformin treatment for 24 weeks. The primary endpoint was the change in HbA1c from baseline to week 24. This clinical trial was the first to directly compare any two SGLT2 inhibitors using a randomized, double-blind, controlled design evaluating effectiveness and safety.
Safety and Effectiveness in Patients with Stage 3 Chronic Kidney Disease (CKD)
A phase 3, randomized, double-blind, placebo-controlled trial evaluated the effectiveness and safety of BRENZAVVY, 20 mg, in adults with type 2 diabetes mellitus, moderate renal impairment (stage 3 CKD) and inadequate glycemic control. 312 adults received BRENZAVVY, 20 mg, or placebo in addition to ongoing hypoglycemic medications for 24 weeks. Eligible patients were stratified based on their estimated glomerular filtration rate (eGFR; either 30 to < 45 mL min-1 per 1.73 m2, stage 3b CKD, or 45 to < 60 mL min-1 per 1.73 m2, stage 3a CKD), baseline HbA1c (> 8.5% or not) or use of insulin. The primary endpoint was the change in HbA1c from baseline to week 24.
Safety and Effectiveness in Patients as an Adjunct to Metformin
A phase 3, randomized, double-blind, placebo-controlled trial evaluated the effectiveness and safety of BRENZAVVY, 20 mg, in adults with type 2 diabetes mellitus as an adjunct to metformin. 317 adults received BRENZAVVY, 20 mg, or placebo in addition to ongoing metformin treatment for 24 weeks. Eligible patients were stratified based on baseline HbA1c (> 8.5% or not) and country of residence. The primary endpoint was the change in HbA1c from baseline to week 24.
An open label group enrolled an additional 34 patients with HbA1c > 10.5 and ≤ 12.0% and was analyzed separately.
Safety and Effectiveness Compared to Glimepiride as an Adjunct to Metformin for Treatment of Type 2 Diabetes Mellitus in Adults
A phase 3, randomized, double-blind, active-controlled, parallel-group designed trial compared the safety and effectiveness of BRENZAVVY, 20 mg, to glimepiride, optimally titrated up to 6 mg, in adults with type 2 diabetes mellitus medicated with metformin (≥ 1500 mg day-1) for at least 8 weeks prior to the screening visit. Patients were eligible if their antidiabetic regimen included another oral hypoglycemic agent (OHA), if they discontinued the second agent for at least 6 weeks prior to entering the 2-week, single blind placebo run-in period that all subjects underwent.
Safety and Effectiveness Compared to Sitagliptin as an Adjunct to Metformin for Treatment of Type 2 Diabetes Mellitus in Adults
A phase 3, randomized, double-blind, active-controlled, parallel-group trial compared the safety and effectiveness of BRENZAVVY, 20 mg, to sitagliptin, 100 mg, in adults with type 2 diabetes mellitus and medicated with metformin (≥ 1500 mg day-1) for at least 8 weeks prior to the screening visit. 386 adults received BRENZAVVY or sitagliptin in addition to ongoing metformin for 24 weeks. Eligible patients were stratified based on their baseline HbA1c (> 8.5% or not). The primary endpoint was the intergroup difference in the change in HbA1c from baseline to week 24.
Cardiovascular Safety Profile
In 2008, FDA published a Guidance for Industry that required sponsors to comply with standards to ensure the cardiovascular safety of products designed to treat diabetes. The Agency established two criteria: a pre-market threshold and a post-approval threshold. To satisfy the first criterion, the upper bound of the 95% confidence interval for the hazard ratio for major adverse cardiovascular events (MACE) caused by the product had to be less than 1.8. For the second criterion, the sponsor had to demonstrate that the upper bound was less than 1.3. The endpoint for the pre-approval standard could include more events than the endpoint for the post-approval standard.