An upcoming phase 2 trial will assess ketamine in up to 36 patients, using change in the Unified Dyskinesia Rating Scale as the primary end point of the study.
The FDA recently approved PharmaTher Holdings’ investigational new drug (IND) application for ketamine in the treatment of levodopa-induced dyskinesia in patients with Parkinson disease (PD), with a phase 2 clinical trial on the way.1
The phase 2 trial will evaluate the safety, efficacy, and pharmacokinetics of ketamine in this population and is expected to begin patient enrollment in the third quarterof 2021. PharmaTher also noted that pending the success of the trial, the company will seek an agreement with the FDA to move to a phase 3 clinical study under the 505(b)(2) regulatory pathway next year.
"The FDA’s acceptance of our IND application for ketamine to treat Parkinson disease is a significant milestone for us. The FDA IND is our first of many we will aim to obtain, and we are one of the few psychedelics-focused biotech companies that have an IND approved by the FDA for a recognized psychedelic drug,” Fabio Chianelli, chief executive officer, PharmaTher, said in a statement.1
PharmaTher intends to enroll a target number of 36 individuals randomized to either ketamine or midazolam (Nayzilam; UCB), the active control, in the phase 2 clinical trial. Investigators will use change in the Unified Dyskinesia Rating Scale (UDysRS) total score from baseline to week 8 as the primary end point.
Secondary end points of the study include the change in total objective scores of the UDysRS, total daily OFF times as assessed by subject-completed 24-hour diaries, and change in the Unified Parkinson’s Disease Rating Scale (UPDRS) total and sum scores of motor and dyskinesia from baseline to week 8.
The trial will be led by Scott Sherman, MD, PhD, director, Movement Disorders Center, University of Arizona, and Torsten Falk, PhD, associate professor of neurology and pharmacology, University of Arizona.
"The IND paves the way for us to expeditiously evaluate ketamine and other psychedelics via the FDA regulatory pathway in various mental illness, neurological and pain disorders. We are committed to building a rich pipeline of novel uses, formulations and delivery methods of psychedelics, and with our FDA IND in place, we now have the foundation in making PharmaTher a global leader in psychedelic-based therapeutics,” Chianelli added.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor-modulating drug, was originally FDA-approved in 1970 as an anesthetic agent, and has since been utilized in various off-label indications.Sherman and Falk were part of research published in 2016 which evaluated low-dose subanesthetic intravenous ketamine infusion in patients with PD. In that study, treatment with ketamine was observed to be tolerable, safe, and had long-term benefits.2
Ketamine has also been shown to reduce treatment-resistant depression and posttraumatic stress disorder symptom severity, as well as reduction of chronic pain states, including migraine headaches. In a preclinical rodent model of levodopa-induced dyskinesias, ketamine (5-20mg/kg) led to long-term dose dependent reduction of abnormal involuntary movements, only when low-dose ketamine was given for 10 hours continuously and not after a single acute low-dose ketamine injection. Sherman and Falk, senior authors on that study, concluded that low-dose, subanesthetic ketamine infusion could lead to fast clinical translation, and could act as a potential therapy for patients with PD who experience depression and comorbid pain states.3