AstraZeneca is advancing its investigational cholesterol-lowering drug AZD0780 through concurrent Phase II and Phase III clinical trials, targeting patients with atherosclerotic cardiovascular disease (ASCVD) and elevated low-density lipoprotein cholesterol (LDL-C) levels.
Phase II Blood Pressure Study Design
The Phase II trial (D7960C00009) represents a multi-center, randomized, double-blind, placebo-controlled crossover study evaluating AZD0780's effect on systolic blood pressure at Week 4. The study utilizes 24-hour ambulatory blood pressure monitoring (ABPM) in participants with ASCVD or risk equivalents and LDL-C ≥ 70 mg/dL who are on stable medication.
Approximately 30 sites across the United States will enroll adult participants, with eligible patients randomized 1:1 to one of two treatment sequences in a crossover design. The study incorporates a 14-day washout period between treatment periods, with participants self-administering AZD0780 or placebo for 29 ± 2 days per period.
The trial protocol includes comprehensive monitoring through outpatient visits on Days -1, 1, 14, 28, and 29 of each period. Serial pharmacokinetic blood samples will be collected predose and up to 7 hours postdose on Day 14 and predose on Day 28 in each period. Safety assessments encompass adverse event monitoring, vital sign measurements, 12-lead electrocardiograms, clinical laboratory tests, and physical examinations.
Phase III Efficacy and Safety Evaluation
The Phase III study (D7960C00012) represents a larger-scale evaluation of AZD0780's cholesterol-lowering capabilities. This randomized, double-blind, placebo-controlled, parallel-group trial will assess LDL-C reduction and safety over 52 weeks of treatment across approximately 470 centers in 21 countries.
The study targets adults ≥ 18 years of age with LDL-C ≥ 55 mg/dL and history of clinical ASCVD, or ≥ 70 mg/dL and at risk for a first ASCVD event. Approximately 2,800 participants will be randomized 1:1 to receive either AZD0780 or matching placebo, administered orally once daily on top of maximally tolerated lipid-lowering regimens including maximally tolerated statin therapy.
Drug Mechanism and Patient Population
AZD0780 is characterized as a small molecule designed to reduce LDL-C levels in blood. The therapeutic approach targets patients with established cardiovascular disease or those at elevated risk for initial cardiovascular events, representing a significant patient population with unmet medical needs despite current statin-based therapies.
Study Oversight and Safety Monitoring
The Phase III trial incorporates robust safety oversight through an independent data monitoring committee that will regularly review accumulating study data, evaluate adverse effects of the investigational medicinal product, and make recommendations regarding study continuation or modification.
The comprehensive clinical development program spans up to approximately 56 weeks for individual participants in the Phase III study, including a screening period of up to 14 days, 52 weeks of treatment, and a 10-day safety follow-up period. The Phase II study includes screening up to 7 days prior to first study intervention administration and a 14-day follow-up period after the last dose in Period Two.
