Ketamine Eases Levodopa-induced Dyskinesia in Phase 2 Study
Treatment with the low-dose painkiller ketamine eased levodopa-induced dyskinesia (uncontrollable body movements) in patients with Parkinson’s disease, according to results from a Phase 2 study sponsored by PharmaTher.
The trial (NCT04912115) evaluated how well a low dose of ketamine that does not induce anesthesia works to reduce levodopa-induced dyskinesia in 30 adults with Parkinson’s.
All patients treated with an intravenous (into-the-vein) ketamine infusion for the study period had a reduction in dyskinesia, as measured by the Unified Dyskinesia Rating Scale.
Low-dose ketamine was well tolerated, and side effects were mild or moderate. No serious side effects were reported.
Based on these findings, the company is preparing to discuss the design of a Phase 3 clinical study with the U.S. Food and Drug Administration (FDA) where it plans to use Ketarx, its own ketamine intravenous product, for a longer treatment period.
“We are very pleased with the results from this clinical study as it gives us further confidence that ketamine can safely and effectively reduce levodopa-induced dyskinesia in patients with Parkinson’s disease and it paves the way for a potential Phase 3 clinical study to support FDA approval via the 505(b)(2) regulatory pathway,” Fabio Chianelli, CEO of PharmaTher, said in a press release.
The 505(b)(2) regulatory pathway is a new drug application that offers a faster route to approval compared to traditional regulatory pathways as it relies partly on studies done previously by other companies.
Dyskinesia is a common side effect of the prolonged use of levodopa, a Parkinson’s treatment that increases the brain’s dopamine levels. Most Parkinson’s patients taking levodopa will develop dyskinesia after 10–12 years of treatment, previous studies have shown.
Ketamine is approved by the FDA as an anesthetic and pain-relieving agent. Prior reporting of five cases showed that low-dose ketamine can reduce levodopa-induced dyskinesia in those with Parkinson’s.
In this Phase 2 study, patients aged 30 to 85 years were randomly assigned to receive either low-dose ketamine or midazolam — a sedative used for anesthesia, trouble sleeping, and severe agitation — for about two months (eight weeks).
Its primary goal was to assess changes in the Unified Dyskinesia Rating Scale total score from the start of the study to the end of treatment. Secondary goals included changes in the Unified Dyskinesia Rating Scale total objective, motor, and dyskinesia scores, and total daily off times after eight weeks of treatment. Off times are periods when symptoms return despite medication use.
“The results of this clinical study further support that ketamine is well-tolerated even in an older population of patients with advanced Parkinson’s disease,” said Scott Sherman, MD, PhD, the study’s principal investigator. Sherman, who is an associate professor of neurology, directs the Movement Disorders Center at the University of Arizona College of Medicine, the Arizona Chapter of American Parkinson’s Disease Association, and the Parkinson’s Disease Program of the HealthSouth Rehabilitation Institute of Tucson.
“This opens the door to a fast-track development of a novel non-surgical treatment for levodopa-induced dyskinesia that will fill a major gap in the existing therapeutic arsenal,” Sherman said.
The company plans to present the full results of the study at a medical congress in June.