Key result
PA32540 resulted in a lower mean percent time intragastric pH >4 over 24 hours compared to EC-omeprazole 40 mg (50.6% vs 57.6%, P=0.004).
Why the study?
Does PA32540 (enteric-coated aspirin 325 mg + immediate-release omeprazole 40 mg) alter intragastric pH control compared to enteric-coated aspirin 325 mg + enteric-coated omeprazole 40 mg in healthy volunteers?
RCT (n=26)
Open-label
randomised
No
Does PA32540 (enteric-coated aspirin 325 mg + immediate-release omeprazole 40 mg) alter intragastric pH control compared to enteric-coated aspirin 325 mg + enteric-coated omeprazole 40 mg in healthy volunteers?
Absolute Event Rate: 50.6% vs 57.6%
p-value: p=0.004
PA32540 provides slightly lower 24-hour acid control and significantly lower omeprazole exposure compared to equivalent doses of enteric-coated omeprazole, appearing similar to 20 mg EC-omeprazole.
PA32540 yields inferior 24-hour acid suppression; challenges equivalence assumptions for this aspirin-omeprazole combination versus separate EC-omeprazole.
BACKGROUND: Aspirin therapy is associated with adverse upper gastrointestinal effects. PA32540 is a coordinated-delivery tablet containing enteric-coated aspirin (EC-ASA) 325 mg and immediate-release (IR) omeprazole 40 mg. 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. AIM: To compare the pharmacodynamic and pharmacokinetic effects of PA32540 (EC-ASA 325 mg + IR-omeprazole 40 mg) vs. enteric-coated (EC)-omeprazole 40 mg. METHODS: This single-centre, open-label, randomised, two-way crossover study in healthy volunteers compared 7 days of once-daily dosing with PA32540 with 7 days of once-daily EC-ASA 325 mg + EC-omeprazole 40 mg dosed concomitantly. The primary endpoint was per cent time intragastric pH >4 over 24 h on Day 7. A key secondary endpoint was determination of the pharmacokinetics of omeprazole and salicylic acid. RESULTS: Twenty-six subjects (mean age 29 years) 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 40 mg (P = 0.004) and geometric least squares mean AUC0-24 for omeprazole was 1446 h*ng/mL for PA32540 and 2558 h*ng/mL for EC-omeprazole 40 mg. Day 7 median Tmax of omeprazole was 0.5 h for PA32540 and 1.25 h for EC-omeprazole 40 mg. CONCLUSION: Total exposure to omeprazole from PA32540 was 57% of that from EC-omeprazole for the same dose amount (40 mg), while absolute difference in 24-h acid control was 7%. Omeprazole exposure and pH control with PA32540 appear similar to EC-omeprazole 20 mg.
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Miner et al. (2013) conducted an RCT in healthy volunteers (n=26). PA32540 (enteric-coated aspirin 325 mg + immediate-release omeprazole 40 mg) vs. enteric-coated aspirin 325 mg + enteric-coated omeprazole 40 mg was evaluated on per cent time intragastric pH >4 over 24 h on Day 7 (p=0.004). PA32540 resulted in a lower mean percent time intragastric pH >4 over 24 hours compared to EC-omeprazole 40 mg (50.6% vs 57.6%, P=0.004).
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