PALM SPRINGS, California — A new sodium channel blocker, CNV1014802, reduces neuropathic pain from lumbosacral radiculopathy, a phase 2 trial shows.
Patients taking the drug improved by about 1 point on the Pain Intensity Numerical Rating Scale (PINRS), where 0 is no pain and 10 is the greatest possible pain.
“We know we’ve got a very exciting compound,” said first author Simon Tate, PhD, chief scientific officer for the drug’s maker, Convergence Pharmaceuticals, which funded the study.
He presented the findings here at the American Pain Society (APS) 34th Annual Scientific Meeting.
Lumbosacral radiculopathy is common, but no treatment has been approved with this indication. “The failure rate has been huge,” said Edward Michna, MD, director of the Pain Trials Center at Brigham and Women’s Hospital, Boston, Massachusetts, who was not involved in the study.
“It’s surprising that they had significant results,” he told Medscape Medical News. “Nobody else has been able to do that.”
CNV1014802 is a novel, smallmolecule, statedependent sodium channel blocker that exhibits potency and selectivity against the Nav1.7 sodium channel, said Dr. Tate.
Previous research showed that CNV1014802 is well tolerated and can be administered at therapeutic doses, without the need for titration, Dr. Tate.
In this study, he and his colleagues wanted to see whether it could help people with radiculopathy pain from lowback injuries.
They recruited people with these symptoms and gave them a placebo for 14 days, during which time they prohibited other drugs. They eliminated from the study 57 patients who responded favorably to the placebo. After this run-in phase, 82 patients remained.
These patients had been experiencing lumbosacral radiculopathy pain for a median of 36 months. Their median score on the Standardized Evaluation of Neuropathic Pain protocol was 9. A score of 4 or more on this test indicates that low back pain is likely to be radicular.
In addition, they had high scores on the McGill Pain Questionnaire for neuropathic pain descriptors, such as shooting/stabbing pain.
At baseline, their mean pain score was 6 on the PINRS.
Forty-one percent had had surgery for back pain or radiculopathy, and 90% had treated their pain with drugs, mainly aspirin, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs).
“We chose the population very carefully,” said Dr. Tate.
But Dr. Michna thought the definition of radiculopathy in the study was less than ideal. “Not everything that’s radicular is radiculopathy,” he said. “If you don’t define the population well, drugs fail.”
The researchers divided the patients in half. One group continued receiving the placebo for another 22 days while the other group switched to 350 mg of CNV1014802 twice a day.
The researchers allowed only 42% of the patients to take adjunctive treatments, mainly NSAIDs, acetaminophen, and gabapentinoids.
After a 13-day washout period, the patients who had been taking the placebo switched to CNV1014802 and vice versa for another 22 days.
Finally, both groups took the placebo for 7 days.
Since some patients dropped out along the way, by the end of the study 79 patients had taken CNV1014802 and 73 had taken the placebo for 22 days.
Both groups of patients felt better after 22 days of placebo or CNV1014802, but the improvement was greater in the CNV1014802 group. The difference was statistically significant and was greater among patients who weren’t allowed to take any other pain relievers.
Table 1. Changes on the 11-Point PINRS
|All randomly assigned patients||–0.84||–0.41||–0.43||.0265|
|Randomly assigned patients not allowed to take adjunctivetreatments||–1.06||–0.33||–0.72||.0039|
The CNV1014802 group also improved more than the placebo group on five other scales. The differences were statistically significant on the Neuropathic Pain Scale and on the Straight Leg Raise test for pain, but only for patients who didn’t get the adjunctive treatment.
The differences on the Oswestry Low Back Disability Questionnaire or the Straight Leg Raise test for angle were not statistically significant, regardless of whether the patients had adjunctive treatment.
The patients taking CNV1014802 had a few more adverse events than the patients taking the placebo, but most of these affected less than 3.5% of the patients.
Table 2. Adverse Events
|Endpoint||CNV1014802 (%)||Placebo (%)|
“Given the diverse sodium channels across the body, the fact their side effect profile was so low is pretty surprising as well,” said Dr. Michna.
Also at the APS meeting, Convergence presented a similar trial of CNV1014802 for trigeminal neuralgia. In this trial, the drug was more effective than placebo with all of the study efficacy endpoints, including measures of pain and global functioning.
Dr. Tate said the company is now planning a phase 2b trial for lumbosacral radiculopathy in which patients take the drug for a longer period.
The study was funded by Convergence Pharmaceuticals. Dr Tate is an employee of Convergence Pharmaceuticals. Dr. Michna has consulted for Pfizer, Purdue Pharma, and Insys Therapeutics.
American Pain Society (APS) 34th Annual Scientific Meeting. Abstracts 387 and 388. Presented May 14, 2015.
Article by: Laird Harrison, Medscape Medical News