Intragastric acidity and omeprazole exposure during dosing with either PA32540 (enteric‐coated aspirin 325 mg + immediate‐release omeprazole 40 mg) or enteric‐coated aspirin 325 mg + enteric‐coated omeprazole 40 mg – a randomised, phase 1, crossover study

Abstract

Aspirin therapy is associated with adverse upper gastrointestinal effects. PA32540 is a coordinated-delivery tablet containing enteric-coated aspirin (EC-ASA) 325mg and immediate-release (IR) omeprazole 40mg. Immediate-release omeprazole (located in outer layer of tablet) is available for instantaneous dissolution rapidly after ingestion, while dissolution of the EC-ASA core is delayed until pH >5.5. To compare the pharmacodynamic and pharmacokinetic effects of PA32540 (EC-ASA 325mg + IR-omeprazole 40mg) vs. enteric-coated (EC)-omeprazole 40mg. This single-centre, open-label, randomised, two-way crossover study in healthy volunteers compared 7days of once-daily dosing with PA32540 with 7days of once-daily EC-ASA 325mg + EC-omeprazole 40mg dosed concomitantly. The primary endpoint was per cent time intragastric pH >4 over 24h on Day 7. A key secondary endpoint was determination of the pharmacokinetics of omeprazole and salicylic acid. Twenty-six subjects (mean age 29years) were enrolled into the study. On Day 7, mean per cent time intragastric pH >4 was 50.6% for PA32540 and 57.6% for EC-omeprazole 40mg (P=0.004) and geometric least squares mean AUC0-24 for omeprazole was 1446h*ng/mL for PA32540 and 2558h*ng/mL for EC-omeprazole 40mg. Day 7 median Tmax of omeprazole was 0.5h for PA32540 and 1.25h for EC-omeprazole 40mg. Total exposure to omeprazole from PA32540 was 57% of that from EC-omeprazole for the same dose amount (40mg), while absolute difference in 24-h acid control was 7%. Omeprazole exposure and pH control with PA32540 appear similar to EC-omeprazole 20mg.