ONO-4474

We examined the efficacy, safety, and tolerability of ONO‐4474 in Japanese patients with osteoarthritis (OA) of the knee. In this multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group comparative study, patients with moderate to severe OA who were refractory to nonsteroidal anti‐inflammatory drugs were orally administered 100 mg of ONO‐4474 twice daily for 28 days. The primary end point was knee pain during walking, assessed by visual analog scale over 24 hours (VAS24). Treatment‐emergent adverse events (TEAEs) and adverse drug reactions were reported for safety. In total, 110 patients were randomized (1:1) to receive placebo or ONO‐4474. The mean (standard deviation) change in VAS24 scores at week 4 was −26.9 (25.0) mm in the ONO‐4474 group and −19.5 (19.6) mm in the placebo group. The difference (ONO‐4474 group − placebo group) in posterior mean change in VAS24 at week 4 was −5.8 (posterior standard deviation, 4.4; 95% confidence interval, −14.3 to 2.8) mm. TEAEs were reported in 41.8% of patients in the ONO‐4474 group and 18.2% of patients in the placebo group. The most common TEAEs in the ONO‐4474 group related to the musculoskeletal system and the peripheral and central nervous systems were myalgia (7.3%), arthralgia (5.5%), dizziness (3.6%), and hypoesthesia (3.6%). Four patients from the ONO‐4474 group and 1 patient from the placebo group discontinued treatment because of AEs; however, none were judged to be serious, and all patients recovered or were recovering after discontinuation. ONO‐4474 is a novel tropomyosin receptor kinase inhibitor that has an analgesic effect in patients with OA.