ITI-214 Safe, Well-tolerated in Mild to Moderate Parkinson’s Patients, Phase 1/2 Trial Shows

Treatment with the experimental oral therapy ITI-214 was safe and well-tolerated in patients with mild to moderate Parkinson’s disease, according to a Phase 1/2 clinical trial.

Trial findings also suggested that ITI-214 may ease motor symptoms in these patients.

The study, “A Phase I/II Clinical Study of  ITI-214, a Novel Phosphodiesterase-I (PDE1) Inhibitor, for the Treatment of Parkinson’s Disease (PD),” was presented during AD/PD 2019 — The 14th International Conference on Alzheimer’s and Parkinson’s Diseases, taking place March 26-31 in Lisbon, Portugal.

ITI-214 is a selective blocker of an enzyme called phosphodiesterase 1 (PDE1), implicated in the breakdown of cAMP and cGMP. These two messenger molecules act within cells of the nervous system in response to diverse signals. Because altered PDE1 activity has been reported in both neurological and cardiovascular diseases, blockers such as ITI-214 are intended to restore its normal function.

Work in rodent models suggested that ITI-214, being developed by Intra-Cellular Therapies, may relieve motor and non-motor symptoms of Parkinson’s. In preclinical studies, the investigational therapy also reduced neuroinflammation through its effect on microglia — key immune cells in the central nervous system — and prevented neurodegeneration.

Data from four Phase 1 trials in healthy volunteers showed that treatment with ITI-214 was generally well-tolerated and safe.

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Researchers are now presenting clinical data from the randomized, double-blind, placebo-controlled Phase 1/2 trial (NCT03387215) that primarily evaluated the safety and tolerability of increasing doses of ITI-214 in patients with mild to moderate Parkinson’s.

As secondary goals, the seven-day Intra-Cellular Therapies-sponsored study assessed the compound’s pharmacokinetics — its absorption, distribution, metabolism, and excretion in the body — as well as biomarkers of inflammation, and motor and non-motor effects through the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale.

The 40 participants (50 years and older) were maintained on stable Parkinson’s therapy. All five doses of ITI-214 — 1, 3, 10, 30, and 90 mg — were found safe and generally well-tolerated. In addition, the findings showed signals of less motor dysfunction and dyskinesia — involuntary, jerky movements — with some of the administered doses.

“Clinical data indicate that ITI-214 is safe and generally well tolerated across a range of doses in patients with mild to moderate [Parkinson’s],” the scientists wrote.

Noting that the signals of clinical improvement warrant further evaluation, the team added that “selective PDE1 inhibition may represent a novel approach for the treatment of motor and non-motor symptoms associated with [Parkinson’s].”

Of note, all seven of the study’s authors are employees of Intra-Cellular.

Besides Parkinson’s, ITI-214 is being evaluated in a Phase 1/2 trial (NCT03387215) in patients with heart failure, which is supported by results showing increased heart contraction strength in dogs and rabbits.