Two multicenter, double-blind, active-controlled, randomized, 24-week studies of DUEXIS were conducted in patients who were expected to require daily administration of an NSAID for at least the coming 6 months for conditions such as the following: osteoarthritis, rheumatoid arthritis, chronic low back pain, chronic regional pain syndrome, and chronic soft tissue pain. Patients were assigned randomly, in approximately a 2:1 ratio, to treatment with either DUEXIS or ibuprofen (800 mg) three times a day for 24 consecutive weeks. A total of 1533 patients were enrolled and ranged in age from 39 to 80 years (median age 55 years) with 68% females. Race was distributed as follows: 79% Caucasian, 18% African-American, and 3% Other. Approximately 15% of the patients in Studies 301 and 303 were taking concurrent low-dose aspirin (less than or equal to 325 mg daily), 18% were 65 years of age or older, and 6% had a history of previous upper gastrointestinal ulcer. Although H. pylori status was negative at baseline, H. pylori status was not reassessed during the trials.

Studies 301 and 303 compared the incidence of upper gastrointestinal (gastric and/or duodenal) ulcer formation in a total 930 patients taking DUEXIS (ibuprofen and famotidine) and 452 patients taking ibuprofen only, either as a primary or secondary endpoint. In both trials, DUEXIS was associated with a statistically significantly reduction in the risk of developing upper gastrointestinal ulcers compared to taking ibuprofen only during the 6 month study period. The data are presented below in Tables 4 and 5. Two analyses for each endpoint were conducted. In one analysis patients who terminated early, without an endoscopic evaluation within 14 days of their last dose of study drug, were classified as not having an ulcer. In the second analysis, those patients were classified as having an ulcer. Both analyses exclude patients who terminated study prior to the first scheduled endoscopy at 8 weeks.

Subgroup analyses of patients who used low-dose aspirin (less than or equal to 325 mg daily), were 65 years and older, or had a prior history of gastrointestinal ulcer are summarized as follows:

Of the 1022 patients in clinical studies of DUEXIS, 15% (213 patients) used low-dose aspirin and the results were consistent with the overall findings of the study. In these clinical studies 16% of patients who used low-dose aspirin who were treated with DUEXIS developed an upper gastrointestinal ulcer compared to 35% of those patients who received only ibuprofen.

The clinical trials primarily enrolled patients less than 65 years without a prior history of gastrointestinal ulcer. Of the 1022 patients in clinical studies of DUEXIS, 18% (249 patients) were 65 years of age or older. In these clinical studies, 23% of patients 65 years of age and older who were treated with DUEXIS developed an upper gastrointestinal ulcer compared to 27% of those patients who received only ibuprofen [see Use in Specific Populations (8.5)].

Of the 1022 patients in clinical studies of DUEXIS, 6% had a prior history of gastrointestinal ulcer. In these clinical studies, 25% of patients with a prior history of gastrointestinal ulcer who were treated with DUEXIS developed an upper gastrointestinal ulcer compared to 24% of those patients who received only ibuprofen.