ROME — A strontium-chloride–based topical agent showed favorable efficacy and safety for the relief of moderate to severe osteoarthritic knee pain in a phase II study.
Known as 2PX for research purposes, this low-viscosity liquid contains 10% strontium chloride hexahydrate as its active ingredient.
It proved significantly more effective than placebo in the 8-week, double-blind, randomized, crossover trial involving 78 patients with moderate to severe knee pain from osteoarthritis that was not controlled by NSAIDs or weak opioids, Dr. Stuart H.R. Ratcliffe reported.
The primary efficacy end point was change from baseline through week 4 in the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain subscale score. The mean 3.9-point drop in the 2PX group was significantly greater than the 2.2-point reduction with placebo.
After 4 weeks, patients were crossed to the other study arm. At 8 weeks, patients on 2PX did better on several secondary end points as well.
They had a mean 2.61-point greater decrease in WOMAC total score and a 1.87-point greater reduction in the physical function subscale, as well as a 0.23-point greater decline in the stiffness subscale, which was of borderline statistical significance.
In addition, the 2PX group demonstrated significantly greater reductions in self-reported pain intensity and greater pain relief, noted Dr. Ratcliffe, director of pain research at MAC (U.K.) Neuroscience Ltd. of Blackpool, England, which conducted the study.
Strontium chloride hexahydrate has an excellent, well-established safety profile. It is used in toothpastes for people with sensitive teeth, he said in an interview.
Indeed, 2PX was very well tolerated in the study. Mild erythema was the only side effect more common with the agent than with saline placebo.
The need for effective pain relief with a low risk of side effects for patients with osteoarthritis has become more pressing in light of the safety concerns surrounding NSAIDs, reported to be the direct cause of 100,000 hospitalizations annually in the United States. Weak opioids are sometimes ineffective, so many osteoarthritis patients rely on strong opioids for symptom relief, with their attendant increased nausea, vomiting, dizziness, and constipation, Dr. Ratcliffe said.
It is a topical with almost no systemic absorption, so “clearly you can add it to any oral medication because there will be no drug-drug interactions. It probably will be a very good add-on therapy, but also safe and efficacious to use by itself in an acceptable proportion of people with osteoarthritis—knee or hand,” he said.
Strontium's mechanism of benefit stems from its antagonistic effect on calcium-driven pathways that are involved in pain and inflammation.
In preliminary studies, 2PX has shown efficacy in neuropathic as well as nociceptive pain conditions. An ongoing, multicenter, phase III clinical trial of topical 2PX in patients with osteoarthritis of the knee is underway, as well as a phase III trial of 2PX for chronic postamputation pain. The agent is applied twice daily with a roll-on applicator.
Disclosures: Dr. Ratcliffe is employed by a company funded to conduct the phase II clinical trial by SantoSolve AS of Oslo, which is developing 2PX.
The mean 3.9-point drop in the 2PX group was significantly greater than the reduction with placebo.
Source DR. RATCLIFFE