BALTIMORE, Md.—The novel therapeutic agent PA65020 (enteric-coated aspirin plus immediate-release omeprazole) significantly reduced gastrointestinal mucosal damage after 28 days of treatment compared with enteric-coated aspirin (EC-ASA) alone. Results of this single-center, phase I, randomized, double-blind study suggest that for at-risk patients requiring analgesic doses of aspirin, PA65020 may be an important option.
John G. Fort, MD, and colleagues of POZEN, Inc., Chapel Hill, N.C., randomized 40 healthy volunteers (Helicobacter pylori negative) 50 years of age or older with normal baseline endoscopy (Lanza score 0) to receive PA65020 (n=20) or EC-ASA 650 mg (n=20) twice daily for 28 days. Each dose of PA65020 was administered as one tablet (fixed-dose of EC-ASA 325 mg and immediate-release omeprazole 20 mg) plus one tablet of EC-ASA 325 mg. Enteric-coated aspirin 650 mg was administered as two EC-ASA 325 mg tablets; total daily dose was 1300 mg.
The primary end point was proportion of subjects with grade 3 or 4 Lanza score at day 28 (≥11 erosions or hemorrhages or any ulcer, defined as a mucosal break ≥3 mm in diameter with depth). Secondary outcomes included proportion of patients with gastric and/or duodenal ulcers at day 28, normal endoscopies at day 28 (Lanza score 0), heartburn assessment, assessment of dyspepsia-associated abdominal pain, and adverse events. Mean age of the patients was 59.6 years in the PA65020 group and 59.9 years in the EC-ASA 650 group. Each group had 16 males and 4 females and all of the patients were white.
Grade 3 or 4 Lanza scores were significantly lower in the PA65020 treatment group compared with the EC-ASA 650 treatment group at both day 14 and day 28 (P<0.001). At day 14, 5% of those in the PA65020 group had a Lanza score of 3 or 4 vs 90% in the EC-ASA 650 group. At day 28, it was 15% and 85%, respectively.
Administration of EC-ASA 1300 mg/day produced significant upper gastrointestinal damage in the majority of healthy volunteers. At day 28, 65% of those in the PA65020 group had Lanza score 0 endoscopies compared with none in the EC-ASA 650 group (P<0.001). No gastroduodenal ulcers occurred in the PA65020 group compared with 40% in the EC-ASA 650 group (P<0.003). Heartburn was reported by 10% of the PA65020 group and 25% of the EC-ASA 650 group, representing a 60% relative decrease with PA65020 treatment.
Most common adverse events were gastrointestinal; primarily dyspepsia (2 per each treatment group), abdominal discomfort (2 in the EC-ASA 650 group vs none in the PA65020 group), and stomach discomfort (3 in the EC-ASA 650 group vs none in the PA65020 group). No differences between groups were observed for mean change from baseline in dyspepsia-associated abdominal pain and no serious adverse events were reported, the investigators concluded in a presentation during the 29th Annual Scientific Meeting of the American Pain Society.