Preliminary safety, tolerability and efficacy of ALGRX 4975 in Osteoarthritis (OA) of the knee

      Literature suggests that intraarticular capsaicin provides potent long-acting inhibition of pain and inflammatory responses in animal models of knee inflammation and arthritis. Sixteen OA patients were randomized to receive single injections of placebo or 10, 100, or 300 μg of purified capsaicin (ALGRX 4975) into the affected knee joint, preceded by intraarticular injection of lignocaine. Total knee replacement was scheduled for 2, 4, 7, or 14 days after injection of study medication. Safety in the injected knee was specifically evaluated by tests of proprioception and pathologic examination of intraoperative biopsy specimens taken during knee replacement surgery. The primary efficacy parameter was a 100 mm visual analog scale (VAS) measuring pain after injection of lignocaine and capsaicin or placebo into the knee. No patient experienced a serious adverse event (AE) or discontinued for an AE. There were no effects of capsaicin injection on proprioception in the injected knee, findings at the site of injection, or the histopathology of intraarticular tissue biopsies taken during surgery. Plasma capsaicin concentrations were low after all capsaicin doses. With 4 subjects/dose group, the median decrease in the VAS from baseline (prior to injection of lignocaine and capsaicin) to just prior to knee replacement was −30.0 mm, −25.5 mm, −28.5 mm, and −3.5 mm in the 10 μg, 100 μg, 300 μg, and placebo groups, respectively. Thus, the average OA pain relief was substantially greater after all doses of capsaicin than after placebo injection, and for up to two weeks after single injection, although the results in these small groups did not reach statistical significance. 10, 100, and 300 μg injections of capsaicin were safe and well-tolerated.