AstraZeneca is advancing two major Phase III clinical trials investigating baxdrostat in combination with dapagliflozin, targeting distinct but related patient populations with cardiovascular and kidney complications. These studies represent significant efforts to address unmet medical needs in patients with complex metabolic and cardiovascular conditions.
Cardiovascular Outcomes Study Design
The first Phase III trial (D6973C00001) focuses on heart failure and cardiovascular outcomes in a high-risk population. The study enrolls men and women aged 40 years and older with type 2 diabetes mellitus, established cardiovascular disease, and a history of hypertension with systolic blood pressure of at least 130 mmHg at screening. Participants must meet predefined serum potassium levels and have at least one additional risk factor for heart failure.
The trial incorporates an optional pre-screening period to help sites identify potentially eligible participants without requiring site visits or informed consent. Following a 14-day screening period, participants not currently treated with SGLT2 inhibitors or treated for less than four weeks enter a run-in period with dapagliflozin 10 mg once daily for at least four weeks but not more than six weeks before randomization.
Site visits are scheduled at approximately 2, 4, 8, 16, and 34 weeks following randomization, with subsequent visits occurring approximately every four months. The study will conclude when the predetermined number of first secondary endpoint events—the composite of hospitalization for heart failure or cardiovascular death—is predicted to have occurred.
Chronic Kidney Disease Trial Protocol
The second Phase III study (D6972C00003) evaluates baxdrostat/dapagliflozin efficacy and safety in participants aged 18 years and older with chronic kidney disease and hypertension. This trial features a more extended treatment period, spanning 24 months of double-blind treatment followed by a 6-week open-label period.
The study design includes a 4-week dapagliflozin run-in period for participants naive to SGLT2 inhibitors at baseline. During the 24-month double-blind period, participants receive either baxdrostat/dapagliflozin combination therapy or dapagliflozin alone. Following the double-blind phase, all participants discontinue baxdrostat or placebo and receive dapagliflozin monotherapy for an additional six weeks.
Visit Schedule and Monitoring
Both trials employ comprehensive monitoring protocols with site visits at 2, 4, 8, and 16 weeks following randomization, followed by approximately every four months thereafter. In the chronic kidney disease study, the 24-month visit marks the discontinuation of baxdrostat or placebo, with participants continuing open-label dapagliflozin for reassessment of glomerular filtration rate for the primary efficacy endpoint.
Continuation Protocols
Both studies incorporate provisions for participants who prematurely discontinue blinded study interventions. In such cases, participants remain in the study and continue receiving open-label dapagliflozin 10 mg, unless they meet dapagliflozin-specific discontinuation criteria. This approach ensures comprehensive data collection while maintaining participant safety throughout the study duration.
The trials emphasize the importance of maintaining scheduled study visits and data collection according to protocol specifications, even in cases of premature intervention discontinuation, reflecting the commitment to generating robust clinical evidence for this combination therapy approach.
