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Purpose: To determine whether a combination tablet of ibuprofen (IBU) plus a high-dose H2RA will decrease ulcer disease in NSAID plus LDA users and improve compliance.
Methods: Two 24-wk double-blind, randomized trials of HZT-501 (DUEXIS), a single-tablet combination of ibuprofen (IBU; 800mg) and famotidine (FAM; 26.6mg) given three times daily were undertaken (REDUCE-1 and REDUCE-2). Patients 40-80 yrs expected to require daily NSAID therapy >= 6 mos with no history of ulcer complications, negative H. pylori stool test and baseline endoscopy (EGD) showing no ulcers and <5 erosions in the UGI tract were randomly assigned in a 2:1 ratio to HZT-501 or IBU 800 mg tablets. Concomitant LDA (<=325 mg daily) and oral anticoagulants (OAC) therapies were permitted. Randomization was stratified based on LDA/OAC therapy and prior ulcer history. Study EGDs were done at 8, 16 and 24 wks of therapy. The predefined population for primary analyses of ulcers was all patients with at least one on-study EGD. Additional safety data included treatment emergent adverse events (TEAEs), clinical laboratory assessments and physical exams.
Results: The studies included 906 and 627 patients. Total patients were 1533, of which 1022 received HZT-501 and 511 received IBU. They included 121 of 812 and 79 of 570 LDA users in their primary analysis populations, respectively. A combined sub-group analysis of the LDA users demonstrated a reduction in UGI ulcers (HZT-501: 14.0% vs. IBU: 34.5%; difference 20.5% [95% CI: 6.5, 34.6]). There were no clinically relevant differences between treatment groups in vital signs, hematology, biochemistry values or physical exams.
Conclusion: HZT-501 reduces NSAID-associated UGI ulcers overall and in the subset of NSAID users taking LDA. TEAEs were balanced across both treatment groups except dyspepsia which was statistically lower for HZT-501 vs. IBU in line with known activity of FAM.