A walking model to assess the onset of analgesia in osteoarthritis knee pain

Summary Objective To assess a walking model utilizing a set of standardized treadmill walks to measure acute analgesic response in osteoarthritis (OA) of the knee. Design Randomized, double-blind, placebo-controlled, multiple dose, three-period crossover study. Patients ≥45 years of age (N=22) with symptomatic knee OA were randomized to naproxen 500mg bid, tramadol/acetaminophen 37.5mg/325mg in forced titration, or placebo in each of three periods. Patients performed multiple 20-minute treadmill walks on Day 1 and Day 3 at a consistent self-selected pace predetermined at screening. Pain intensity (PI) during the walks was assessed on an 11-point numerical rating scale at 0, 3, 6, 9, 12, 15, 18, and 20min. The primary endpoint was the time-weighted average (TWA) change from baseline PI on Day 3 for the two self-paced walks for the active treatments vs placebo. Time to moderate pain (TTMP) was a key secondary endpoint. Results Compared with placebo, the TWA change from baseline PI on Day 3 was significantly better with tramadol/acetaminophen ( P =0.043) but not with naproxen ( P =0.089). TWA change from baseline on Day 1 was also significantly better with both tramadol/acetaminophen ( P =0.001) and naproxen ( P =0.048) compared with placebo. TTMP was significantly better for tramadol/acetaminophen and naproxen than placebo ( P P =0.015) for walks on Day 1 after a single dose and on Day 3. Conclusions This novel OA pain model was able to discriminate both tramadol/acetaminophen and naproxen from placebo after single and multiple doses. ClinicalTrials.gov identifier: NCT00772967.