Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg combination tablets (tramadol/APAP) as add-on therapy for subjects with osteoarthritis (OA) pain inadequately controlled by COX-2 nonsteroidal antiinflammatory drugs (NSAID).

METHODS: This 91-day, multicenter, randomized, double-blind, placebo-controlled trial enrolled subjects with symptomatic OA for >/= 1 year who experienced at least moderate pain [visual analog scale (VAS) score >/= 50/100 mm] despite treatment with stable doses of celecoxib (>/= 200 mg/day) or rofecoxib (>/= 25 mg/day). Tramadol/APAP or matching placebo was titrated to 4 tablets/day on Day 10 and thereafter as needed up to 8 tablets/day. The primary efficacy measure was final VAS score; secondary measures included final pain relief rating scores, subject/investigator overall medication assessments, rate and time to discontinuation due to lack of efficacy, and selected quality-of-life/physical functioning scores.

RESULTS: Of 307 subjects randomized, 306 taking celecoxib (56.5%) or rofecoxib (43.5%) were included in the intent-to-treat population (n = 153 tramadol/APAP, 153 placebo). Mean final VAS scores for tramadol/APAP plus COX-2 NSAID were significantly lower than placebo plus COX-2 NSAID (41.5 vs 48.3; p = 0.025) and mean final pain relief rating scores were significantly higher (p = 0.002). Subjects taking tramadol/APAP showed significant improvements compared with placebo in subject/investigator medication assessments, as well as in the WOMAC Physical Function and the Medical Outcome Study Short Form-36 Role-Physical measures. The most common treatment-related adverse events for tramadol/APAP were somnolence (6.5%), nausea (4.6%), and constipation (3.3%). Mean tramadol/APAP dose was 4.1 tablets (154 mg tramadol/ 1332 mg APAP).

CONCLUSION: Tramadol 37.5 mg/APAP 325 mg combination tablets were effective and safe as add-on therapy with COX-2 NSAID for treatment of OA pain.