Safety evaluation of nabumetone in United States clinical trials

A total of 1,924 persons (rheumatoid arthritis, 835; osteoarthritis, 1,073; volunteers, 16) received nabumetone in United States clinical trials. Nine hundred eighty-eight patients have received nabumetone treatment for periods of more than one year, and 375 patients have received treatment for longer than two years. Four hundred eighty patients over 65 years of age have received treatment with nabumetone, and 224 of these elderly patients have received treatment for periods of more than one year. The nabumetone dose most commonly used in all double-blind trials was 1,000 mg at night. In long-term, open-label studies, which were usually extensions of the double-blind trials, patients could increase the dose to 2,000 mg per day. Nine hundred nineteen patients received doses of more than 1,000 mg per day. Adverse experience information was collected at each visit, including information for some patients receiving treatment for more than three years. Laboratory data were collected periodically throughout the trials, and the data were assessed for trends over time. The adverse experience pattern observed for nabumetone is similar to that described for clinical trial data for other nonsteroidal anti-inflammatory drugs. However, it is noteworthy that the pattern observed for nabumetone is from clinical trials with approximately 1,000 patients receiving treatment for periods of one year or more. This long-term patient exposure in clinical trials far exceeds long-term clinical trial data for other agents. The types and frequencies of adverse experiences reported by persons treated with nabumetone are relatively constant over the long time period covered by these trials. Also, the adverse experience patterns remained generally constant over time for various populations: all patients, patients 65 or older, female patients, male patients, and patients who received an increased dose of nabumetone. Although some statistically significant trends were detected for some laboratory parameters, there was little indication of significant clinical patterns. Although there were patients with individually important laboratory values, nabumetone was not associated with clinically important adverse laboratory patterns. Overall, the adverse experience data and laboratory data indicate that nabumetone is safe for the treatment of adult patients with rheumatoid arthritis or osteoarthritis.