Clinical evaluation of a new controlled-release formulation of naproxen in osteoarthritis and rheumatoid arthritis

A two-part multi-centre study was carried out to assess the efficacy and tolerability of a new controlled-release (CR) naproxen tablet in the treatment of osteoarthritis and rheumatoid arthritis. Patients already receiving naproxen on a regular basis were first enrolled in a 6-week randomized double-blind trial comparing the controlled-release tablet (750 mg or 1000 mg once-a-day) to the standard marketed tablet (375 mg or 500 mg twice-a-day). At the end of this phase, patients in both treatment groups were eligible to enter the long-term phase involving 28 weeks of open-label treatment with controlled-release naproxen at the previously established dose level (750 mg or 1000 mg once-a-day). A total of 404 patients entered the initial double-blind phase, 320 of whom continued into the open-label phase. Twenty-nine (14%) naproxen patients and 23 (11%) naproxen CR patients were withdrawn prematurely from the double-blind phase, 87 (27%) patients from the open-label phase. Parameters of efficacy and tolerability were evaluated at base-line, during the double-blind phase (after 3 and 6 weeks of treatment), and during the open-label phase (after 20 and 34 weeks of treatment). The entire study population showed significant improvements in overall disease activity and severity of pain, but with no statistically or clinically significant differences between the two treatment groups; nor were there significant differences among treatments in incidence of adverse events. The patients treated with naproxen CR for an additional 28 weeks showed either no change or continued improvement in arthritic symptoms and no signs of toxicity. It was concluded that, in osteoarthritis and rheumatoid arthritis patients, once-a-day controlled-release naproxen tablets can be substituted for standard naproxen tablets without loss of efficacy or tolerability.