Pa, a Novel Combination of Delayed Release (DR) Aspirin (ASA) and Immediate-Release (IR) Omeprazole, Is Associated with a Decreased Risk of Gastroduodenal Mucosal Injury

Abstract

Purpose: To evaluate via endoscopy the gastroduodenal effects of the fixed combination tablet of DR ASA 325 mg and IR omeprazole (20 or 40 mg). Methods: We conducted 3 Phase I, single-blind, randomized, controlled trials in healthy volunteers (>50 yrs) with normal baseline endoscopy (Lanza score 0). Two studies evaluated PA32520 (DR ASA 325 mg + IR omeprazole 20 mg) vs. either enteric-coated (EC)-ASA 81 mg or 325 mg. The third study compared PA32540 (DR ASA 325 mg + IR omeprazole 40 mg) with EC-ASA 325 mg. All medications were dosed once daily for 4 weeks. The primary endpoint was the proportion of subjects with Grade 3 or Grade 4 Lanza scores at Week 4. Additional assessments included incidence of gastric or duodenal ulcers (GU/DU) at 4 weeks and pharmacokinetics. Data were pooled across the 3 studies. Results: A total of 240 subjects participated. As shown in the Figure, Grade 3 or 4 Lanza scores and the incidences of GU/DU for the PA products were lower than for EC-ASA. With regard to Grade 3 or 4 Lanza scores: PA32520 vs. EC-ASA 81 mg (9.9 vs. 20.5%, P= 0.151); PA32520 vs. EC-ASA 325 mg (9.9% vs. 42.5%, P < 0.001); PA32540 vs. EC-ASA 81 mg (2.5% vs. 20.5%, P= 0.014); PA32540 vs. EC-ASA 325 mg (2.5% vs. 42.5%, P < 0.001). With regard to the incidence of GU/DU: PA32520 vs. EC-ASA 81 mg (2.5% vs. 5.1%, P= 0.595); PA32520 vs. EC-ASA 325 mg (2.5% vs.13.8%, P= 0.009); PA32540 2.5% vs. EC-ASA 81 mg (2.5% vs. 5.1%, P= 0.615); PA32540 vs. EC-ASA 325 mg (2.5% vs. 13.8%, P= 0.059). Plasma salicylic acid pharmacokinetics was similar following dosing with PA32520 or PA32540 and EC-ASA 325 mg following both single-dose and repeat-dose administration.FigureConclusion: Gastroduodenal Grade 3 or 4 Lanza scores and incidence of GU/DU for EC-ASA were dose-related. The fixed dose combination of DR ASA and IR omeprazole was associated with a significant reduction in gastroduodenal Grade 3 or 4 Lanza scores and GU/DU that were dose-related to the proton pump inhibitor. PA32540 demonstrated the least gastroduodenal damage and may provide an important option for at-risk patients who require long-term ASA therapy.