Gastric Ulcers

February 18, 2013

Pozen released results from two phase III trials of PA32540 for the treatment of endoscopic gastroduodenal ulcers. The blinded, randomized, multicenter studies enrolled 1,049 patients with previous cerebrovascular disease, who were prescribed daily aspirin (325mg) for at least three months for secondary prevention of cardiovascular events. Subjects received either once-daily PA32540 or enteric-coated aspirin 325mg. Post-hoc analysis of subjects with a history of transient ischemic attack or stroke, long-term treatment with PA32540, compared to enteric-coated aspirin, was associated with a significantly reduced rate of endoscopic gastroduodenal ulcers (2.0% vs. 12.4%, respectively; p=0.005). Furthermore, 85.1% of subjects on enteric-coated aspirin reported adverse events compared to 71.8% of subjects on PA32540. The drug was well tolerated. The most frequent adverse events were GI tract and include dyspepsia, erosive gastritis and gastritis.

March 26, 2012

POZEN released results from two phase III trials of PA32540, a coordinated-delivery tablet of immediate-release omeprazole and delayed release aspirin, under development for the secondary prevention of cardiovascular disease in subjects at risk for aspirin-induced ulcers. The randomized, double-blind, multi-center studies enrolled 1,049 subjects at risk for developing aspirin-associated ulcers and already taking aspirin at a dose of 325 mg once daily for at least three months. The subjects received treatment with either PA32540 or 325 mg enteric-coated aspirin once daily. The primary endpoint, a significant reduction in the cumulative incidence of gastric ulcers following administration of PA32540 versus 325 mg enteric-coated aspirin over six months, was met in both studies. Secondary endpoints were also reached, including a reduction in gastroduodenal ulceration as well as a reduction in discontinuation due to upper gastrointestinal adverse events.

April 4, 2011

Pozen issued results from the phase I trial of PA32540, a tablet for the secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers. The randomized, open-label, two-arm crossover study, Co-Rx, was designed to compare PA32540 to current standard of care, Prilosec, both in conjunction with clopidogrel. Thirty healthy subjects were treated with one of the following: A) PA32540 in the morning plus clopidogrel (300 mg) over 10 hours later on day 1, and PA32540 in the morning plus clopidogrel (75 mg) 10 hours later on days two through seven; B) enteric-coated aspirin (81 mg) plus clopidogrel (300 mg) plus Prilosec (40 mg) all in the morning on day 1 followed by enteric-coated aspirin (81 mg) plus clopidogrel (75 mg) plus Prilosec (40 mg) all in the morning on days two through seven. Each treatment was separated by a 14 day washout period. The primary endpoint was the percent inhibition of platelet aggregation (IPA) after morning dosing on day seven of each period. The PA32540 treatment arm resulted in a significantly greater IPA than the standard of care arm, with an approximate 20% improvement in the anti-clotting effects.

July 13, 2009

Sucampo issued positive results from a phase II trial of cobiprostone for the prevention of gastric ulcers and other gastrointestinal injuries associated with non-steroidal anti-inflammatory drugs (NSAIDs). This 12-week, double-blinded, randomized, dose-ranging and placebo-controlled study enrolled 124 subjects in the US. All the subjects received 500 mg of naproxen twice a day. There were four treatment cohorts: one cohort received placebo while the other three cohorts received 18 mcg of cobiprostone either once, twice or three times a day (daily totals of 18, 36 or 54 mcg, respectively). The primary endpoint was a reduction in the incidence of ulcers at week 12. The subjects receiving the 54 mcg dose experienced a 50.0% reduction in the overall incidence of gastric ulcers when compared to the placebo arm. Cobiprostone also resulted in an overall statistically significant reduction in the number of gastric erosions through the treatment period of twelve weeks compared to placebo. The reduction of gastric erosions through Week 12 was dose dependent, with 36 mcg and 54 mcg demonstrating statistical significance. The time-to-onset of all ulcer or erosion development was delayed in the cobiprostone cohorts with overall statistical significance across the 12 week treatment period. Treatment was well tolerated.

October 27, 2008

AstraZeneca released positive results from a clinical trial of Nexium (esomeprazole) for the treatment of peptic ulcer re-bleeding. This study enrolled 767 subjects across Europe, Africa and Asia who had received successful endoscopic treatment to stop peptic ulcer bleeding. The subjects were randomized to first receive an intravenous (i.v.) infusion of esomeprazole 80 mg over 30 minutes followed by 8 mg i.v./hour for 72 hours, and then receive 40 mg oral treatment for 27 days. A parallel placebo-controlled group received an i.v. infusion of placebo before the same 27-day period of oral treatment with esomeprazole. The results of the study demonstrated that statistically significantly fewer subjects treated with esomeprazole experienced ulcer re-bleeding compared with placebo both at 72 hours (5.9% versus 10.3%, P=0.026) and at seven days (7.2% versus 12.9%, P=0.0096). When examined over a 30 day period, esomeprazole was shown to significantly reduce the number of subjects re-bleeding by almost half compared to placebo (7.7% versus 13.6%, P=0.0092). In addition, all subjects receiving esomeprazole required significantly fewer interventions by day 30, with 6.4% needing endoscopic re-treatment compared with 11.6% in the placebo group (P=0.037). Overall, the esomeprazole group required significantly fewer days in hospital due to re-bleeding compared to the placebo group (284 days versus 500 days, P=0.008). Regulatory filings are currently under review by the FDA and EMEA.