A Phase 1/2 clinical trial evaluating ITI-214 in patients with Parkinson’s disease (PD) has begun enrolling patients, Intra-Cellular Therapies announced.
ITI-214 is a potent and selective inhibitor of the phosphodiesterase 1 (PDE1) enzyme, which is involved in the degradation of both cAMP and cGMP (cyclic nucleotides). These are within-cell messengers for various signals in the nervous system. PDE1 activity is often high when disease is present, and PDE1 inhibitors are designed to re-establish normal function.
It has been shown that ITI-214 is generally well-tolerated and has a favorable safety profile. The results that led to these discoveries came from four Phase 1 clinical trials involving healthy subjects and schizophrenia patients.
Additionally, studies using animal models reported that neurodegeneration and neuroinflammation were reduced when PDE1 was inhibited, which suggests a possible use for ITI-214 in neurodegenerative diseases, like PD. PDE1 inhibitors also were shown to increase the effect of L-DOPA and other dopamine replacement therapies for motor symptom control, while blocking the adverse involuntary muscle movements induced by these treatments.
The newly-started ITI-214-195 Phase 1/2 trial is a double-blind, placebo-controlled, multiple ascending dose study (NCT03257046). The goal is to evaluate ITI-214’s safety and tolerability in idiopathic PD patients. To do so, researchers randomly will assign PD patients who are on stable PD therapy, to placebo or ITI-214 (1, 3 or 10 mg administered orally once a day for seven days).
The trials’ secondary objectives include the study of the drugs’ absorption, distribution, metabolism, and excretion; the investigation of ITI-214’s usefulness as control therapy for PD motor fluctuations and non-motor symptoms, such as daytime sleepiness. The team also will look for biological markers of disease progression, like those associated to inflammation.
“ITI-214 is a potent and selective phosphodiesterase 1 (PDE1) inhibitor. Following the favorable safety and tolerability results in our Phase 1 program, we are pleased to announce the advancement of ITI-214 for the treatment of patients with Parkinson’s disease,” Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies, said in a press release. “This study is designed to evaluate the safety and tolerability of ITI-214 in this patient population, as well as evaluate the ability of ITI-214 to treat both motor and non-motor symptoms associated with Parkinson’s disease and to provide a framework for future trials to assess disease modification.”