The high‐purity synthetic trans‐capsaicin CNTX‐4975 provides dose-dependent reduction in knee osteoarthritis (OA)-associated pain, as shown in the results of a phase II study.

The study randomized 172 patients aged 45–80 years to receive a single intra-articular injection of placebo (n=69), or CNTX‐4975 at 0.5 mg (n=33) or 1.0 mg (n=70). All patients had radiographic evidence of knee OA (Kellgren/Lawrence [K/L] grade 2–4).

Researchers evaluated efficacy in terms of the area under the curve (AUC) for change from baseline in daily Western Ontario and McMaster Universities Osteoarthritis Index pain with walking score (range 0–10; 0=none and 10=extreme) through week 12. They also performed a similar AUC analysis of outcomes in patients receiving CNTX‐4975 0.5 mg, as well as evaluations extending to 24 weeks.

Week-12 results revealed greater reductions in the AUC for the pain score with both CNTX‐4975 doses than with placebo (0.5 mg: least squares mean difference [LSMD], −0.79, 90 percent CI, −1.5 to −0.06; p=0.0740; 1.0 mg: LSMD, −1.6, −2.2 to −1.0; p<0.0001).

Significant improvements were maintained at week 24 in the 1.0-mg dose group (vs placebo: LSMD, −1.4; p=0.0002) but not in the group that received the 0.5 mg dose (LSMD, −0.6, −1.3 to 0.15; p=0.19).

Treatment‐emergent adverse events were similar, occurring in 30 percent of patients in the placebo group, 47 percent in the 0.5-mg dose group and 30 percent in the 1.0-mg dose group. The events were generally mild (19 percent, 29 percent and 20 percent) or moderate (11 percent, 18 percent and 10 percent) in severity. There were no deaths reported.

The present data support further clinical development of CNTX‐4975.