PN400 Significantly Improves Upper Gastrointestinal Tolerability Compared with Enteric-Coated Naproxen Alone in Patients Requiring Chronic NSAID Therapy: Results from Two Prospective, Randomized, Controlled Trials

Purpose: Upper gastrointestinal (UGI) tolerability and patient satisfaction are important issues that impact persistence with prescribed chronic NSAID therapy. Two Phase 3 studies evaluated the UGI efficacy and safety of PN400, a fixed-dose combination designed to provide sequential delivery of immediate-release (IR) esomeprazole (20 mg) and enteric-coated (EC) naproxen (500 mg), compared with EC naproxen (500 mg) alone in at-risk patients. Methods: Two multicenter studies enrolled H. pylori-negative patients requiring chronic NSAID therapy, at risk of ulcers (18-49 yrs with a history of gastric ulcer [GU] or duodenal ulcer [DU] within the past 5 yrs or ≥50 yrs). Patients received PN400 BID or EC naproxen BID for 6 mos. The cumulative incidence of GUs (1° endpoint) was significantly lower in the PN400 groups in both studies. We report key 2° UGI tolerability endpoints, including the following Patient Reported Outcomes (PROs): Severity of Dyspepsia Assessment (SODA) subscales (pain intensity, non-pain symptoms, and satisfaction), and the proportion of heartburn-free patients assessed at baseline, 1, 3, and 6 mos; and the Overall Treatment Evaluation for Dyspepsia (OTE-DP) rating scale, assessed at final visit. In addition, the proportion of patients discontinuing due to NSAID-associated UGI AEs (including DU) was investigated. Results: Patients were randomized to receive PN400 or EC naproxen (Study A 438 patients; Study B 423 patients). Patients treated with PN400 reported significantly improved SODA scores in all 3 domains after 6 mos vs. EC naproxen (Table). PN400 was associated with a significantly greater proportion of heartburn-free patients at 1, 3 and 6 mos, and with a greater response in the OTE-DP scale vs. EC naproxen in both studies. A preliminary assessment of pooled data suggested that changes from baseline in OTE-DP and SODA scores trended in a similar direction and that the differences may have clinical relevance. Significantly fewer patients discontinued due to prespecified UGI AEs/DUs in the PN400 groups vs. the EC naproxen groups (Study A 3.2% vs. 12.0%, p<0.001; Study B 4.8% vs. 11.0%, p=0.009).TableConclusion: PN400 is associated with better UGI tolerability relative to EC naproxen, as measured by PROs and discontinuation rates due to UGI AEs/DUs. Based on its formulation, PN400 may provide a treatment option for at-risk patients and clinically impact long-term NSAID therapy and utilization. Disclosure: Prof Goldstein - Research grants: Pfizer; AstraZeneca; TAP; Novartis; Pozen; Takeda/Sucampo; GlaxoSmithKline; Logical Therapeutics, Consulting fees: Pfzier; AstraZeneca; TAP; Novartis; Pozen; Takeda/Sucampo; GlaxoSmith-Kline; Given; Merck; Amgen; Astellas Pharma US; PLX; Proctor & Gamble; Logical Therapeutics; Horizion; Wyeth. Speaker's Bureau: Pfizer; AstraZeneca; TAP; Novartis; Pozen; Takeda/Sucampo. Dr Hochberg - Research support: American College of Rheumatology, National Institutes of Health. Consultant: Allergan Sales, LLC, Amgen, AstraZeneca, Bayer Health Care, Bristol Myers Squibb, Bioiberica, CaloSyn Pharma, Eli Lilly, Endo Pharmaceuticals, Gerring Pharmaceuticals, Genzyme Corporation, Hoffman-La Roche, Merck Seronoa, NicOx Inc, Novartis, Pfizer, Pozen, Sanofi-Aventis, Savient, UCB, Wyeth, Zelos Therapeutics. Member of DSMB: National eye institute, Novartis. Dr Fort - Stocks: Pozen Inc. Employee of Pozen Inc. Dr Crawley - Employee of AstraZeneca Dr Sostek - Employee of AstraZeneca. This research was supported by an industry grant from These studies were sponsored by POZEN Inc.