Efficacy, safety, and tolerability of CNTX-4975 in subjects with moderate to severe knee pain associated with osteoarthritis: 12-week results of a randomized, double-blind, placebo-controlled, phase 2b study

INTRODUCTION: A 24‐week study of CNTX‐4975 (highly purified, synthetic trans‐capsaicin) was conducted in subjects with moderate to severe osteoarthritisassociated knee pain. Twelve‐week results are reported. METHODS: Subjects 45‐80 years with stable moderate to severe knee pain were randomized to single intraarticular injections of placebo or CNTX‐4975 0.5mg or 1.0 mg. Assessments included change from baseline in WOMAC Question A1 weekly pain with walking; index knee stiffness (WOMAC B); and physical function (WOMAC C). A mixed model for repeated measures was used to analyze week 12 primary timepoint assessments (p=.10). Treatment‐emergent AEs (TEAEs) were recorded. RESULTS: At week 1 (N=172), mean WOMAC Question A1 pain scores were significantly lower for CNTX‐4975 1.0 mg vs placebo (p=0.025) and remained significant at all remaining weeks (p≤0.005). At week 12, LS mean (SE) changes were ‐ 2.86 (0.365) (placebo) and ‐4.38 (0.364) (CNTX‐4975 1.0 mg); difference: 1.52 (0.419), p<0.001. CNTX‐ 4975 0.5 mg vs placebo was significant at week 12 and the majority of timepoints after week 3. Significant improvements in knee stiffness and physical function were observed at weeks 4, 8, and 12 for CNTX‐4975 1.0mg vs placebo (all p≤0.05). TEAEs were reported by 29% (placebo), 47% (CNTX‐4975 0.5 mg), and 28% (CNTX‐4975 1.0 mg) of subjects. TEAEs >5% were arthralgia for placebo and CNTX‐4975 1.0mg (both <6%) and joint effusion, arthralgia, upper respiratory tract infection, and hepatic enzyme increase for CNTX‐4975 0.5 mg. CONCLUSIONS: CNTX‐4975 1.0mg was well tolerated and effective in improving moderate to severe osteoarthritis‐associated knee pain.