BARCELONA, SpainIntrathecal administration of the selective neuronal channel blocker SNX-111 via an external pump proved safe and feasible in 11 patients with chronic intractable pain. More than half of the group saw an improvement in pain control, William Brose, MD, reported at a meeting of the International Association for the Study of Pain.
Dr. Brose, director of the Pain Management Center, Stanford University, presented the findings from the Stanford site, the highest enrolling center of the six US centers participating in the phase I/II trial. SNX-111, being developed by Neurex Corporation (Menlo Park, Calif), is a synthetic polypeptide initially identified in the venom of the marine snail (Conus magus).
Five Cancer Patients
Of the 11 patients, five were terminally ill with cancer; the other six had nonmalignant pain, one with AIDS neuropathy. All participants had failed standard analgesic therapies, including intrathecal opioids.
After enrollment in the study, the patients were switched from whatever combined spinal and systemic medication they had been receiving to an analgesic regimen that included intravenous morphine(Drug information on morphine). The patients opioid doses were individually titrated to achieve the optimal effect; they were then started on SNX-111, with the dose titrated upward every 24 to 48 hours for up to 7 days.
Efficacy was assessed every 4 hours by the Visual Analog Scale Pain Intensity (VASPI) and the Visual Analog Scale Pain Relief (VASPR), with the maximal analgesic effect being the greatest decrease in mean daily VASPI score from baseline. Decrease in opioid use was a secondary measure of efficacy.
Six of the 11 patients reported marked improvement in VASPI (60% reduction from baseline), and all six of the responding patients also had a marked reduction in opioid dosing (99% median reduction), Dr. Brose said.
The most common adverse events determined to be possibly or probably related to SNX-111 were dizziness and nystagmus (each reported by four patients), and headache, confusion, blurry vision, and orthostatic hypotension (each reported by three patients). All of these effects resolved with dose reduction or drug discontinuation. Two patients developed bacterial meningitis related to use of the external pump and catheter, and both cases resolved with antibiotic therapy. In an interview, Dr. Brose said that these infections were due to staff unfamiliarity with the delivery technique at the beginning of the study. In one case, he said, a disconnected catheter was reconnected after falling on the floor; the other was related to inadvertent infusion of some nonsterile medications into the catheter.
These data and results from other sites form the basis for the ongoing phase III studies of the agent for chronic pain.