Subjects with OA of the knee who complete a washout of all pain medication will be randomized to either a topical NSAID gel formulation (active study drug) or placebo. Study drug or placebo will be applied twice a day to the osteoarthritic knee during a 4-week treatment period. Subjects will receive acetaminophen for rescue medication as needed to treat pain during the treatment period. Subjects will report pain intensity, drug application information and use of rescue medication every day and complete the WOMAC LK3.1 OA Index and a Patient Global Assessment at clinic visits. Safety assessments include adverse events, skin irritation assessments, clinical laboratory tests, physical examinations and vital signs.