Lenrispodun (also known as ITI-214) is being evaluated as an adjunctive therapy for [Parkinson's disease](/diseases/parkinsons-disease) patients experiencing motor fluctuations. This Phase 2 trial is sponsored by [Intra-Cellular Therapies, Inc.](/companies/intra-cellular-therapies)[@nct05766813].
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Trial Overview
Mermaid diagram (expand to render)
Lenrispodun (also known as ITI-214) is being evaluated as an adjunctive therapy for [Parkinson's disease](/diseases/parkinsons-disease) patients experiencing motor fluctuations. This Phase 2 trial is sponsored by [Intra-Cellular Therapies, Inc.](/companies/intra-cellular-therapies)[@nct05766813].
Lenrispodun is an investigational drug developed by Intra-Cellular Therapies, Inc. as an adjunctive therapy for Parkinson's disease patients experiencing motor fluctuations. The drug completed a Phase 2 clinical trial (NCT05766813) evaluating its efficacy and safety in patients with levodopa-induced dyskinesia and wearing-off symptoms.
Intra-Cellular Therapies is a pharmaceutical company known for developing central nervous system therapies, including the FDA-approved drug cariprazine (Vraylar) for schizophrenia and bipolar disorder. Their pipeline includes several phosphodiesterase inhibitors targeting various CNS disorders.
Study Details
| Field | Details | |-------|---------| | NCT Number | NCT05766813 | | Phase | Phase 2 | | Status | Recruiting | | Start Date | March 13, 2023 | | Primary Completion | September 2025 (Estimated) | | Study Completion | October 2025 (Estimated) | | Sponsor | Intra-Cellular Therapies, Inc. | | Enrollment | 132 patients (estimated) |
Study Design
The trial was designed as a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study:
Treatment Period: 4 weeks
Randomization: 1:1 ratio (Lenrispodun 30 mg vs. placebo)
Duration: 4-week double-blind treatment period following screening
Background Therapy: Given as adjunctive to [levodopa](/therapeutics/levodopa)-based therapy
Eligibility Criteria
Inclusion Requirements
Age ≥40 years
Body mass index of 19.0-40.0 kg/m²
Parkinson's disease consistent with UK Parkinson's Disease Society Brain Bank criteria
Hoehn and Yahr stage 2 or 3 when ON
Stable levodopa regimen (≥100 mg three times daily) for ≥4 weeks
Presence of wearing-off symptoms and levodopa-induced dyskinesia
At least 2½ hours OFF time during waking hours on 3 consecutive days
Caregiver required if necessary
Key Exclusion Criteria
Other parkinsonism (progressive supranuclear palsy, multiple system atrophy, drug-induced parkinsonism)
Late-stage PD with severe dyskinesia
Dementia (MMSE ≤24)
CYP3A4 modulators
Daily NSAIDs (except aspirin)
MAO-A inhibitors
PDE5 inhibitors
Alpha blockers
Mechanism of Action
While the specific mechanism of action for lenrispodun has not been fully disclosed in public literature, the drug is being developed within Intra-Cellular Therapies' phosphodiesterase inhibitor pipeline. Based on the company's research focus and the trial's target indication (motor fluctuations and dyskinesia), the mechanism likely involves:
Potential Mechanisms
Phosphodiesterase Inhibition: Modulation of cyclic nucleotide signaling (cAMP/cGMP) in the basal ganglia
Striatal Function: Improvement in dopaminergic signaling in the striatum
Dyskinesia Reduction: Reduction of levodopa-induced dyskinesia through downstream effects on motor circuits
The basal ganglia motor circuit relies heavily on proper cAMP signaling for regulating movement. Phosphodiesterase inhibitors can modulate this pathway, potentially reducing the dysregulated signaling that leads to dyskinesia.
Outcome Measures
Primary Outcome
Hauser Diary - Day 29
Measures ON/OFF time fluctuations in 30-minute intervals
Patients characterize status as Asleep, OFF, ON without dyskinesia, ON with non-troublesome dyskinesia, or ON with troublesome dyskinesia
Part I: Non-motor Aspects of Experiences of Daily Living
Part II: Motor Aspects of Experiences of Daily Living
Part III: Motor Examination
Part IV: Motor Complications
Clinical Significance
Addressing Motor Complications
Motor fluctuations (wearing-off phenomenon) are a common complication of long-term [levodopa](/therapeutics/levodopa) therapy in Parkinson's disease. As the disease progresses, patients experience decreasing duration of benefit from each levodopa dose, leading to predictable ON/OFF cycles.
Wearing-Off Phenomenon: The gradual decrease in levodopa efficacy as PD progresses
Levodopa-Induced Dyskinesia: Involuntary movements that develop with long-term levodopa use
Adjunctive Therapy: Adding a non-levodopa agent to improve existing treatment outcomes
Unmet Medical Need
Current treatments for motor fluctuations include:
Adjusting levodopa dosing frequency
Adding dopamine agonists
Adding MAO-B inhibitors
Adding COMT inhibitors
Deep brain stimulation
There remains a significant need for novel agents that can reduce dyskinesia without compromising motor control.
Lenrispodun represents a novel approach to managing these fluctuations through its mechanism (likely dopamine-related modulation), potentially offering improved symptom control when added to standard levodopa therapy.
Pipeline Context
Intra-Cellular Therapies has been developing multiple CNS drugs targeting phosphodiesterases. Their pipeline approach focuses on:
Novel PDE inhibitors with improved brain penetration
Drugs with favorable side effect profiles
Targeting specific phosphodiesterase isoforms for optimal effect
[Lenrispodun as Adjunctive Therapy in the Treatment of Patients With Motor Fluctuations Due to Parkinson's Disease (NCT05766813)](https://clinicaltrials.gov/study/NCT05766813)
[Intra-Cellular Therapies Clinical Development Pipeline](https://www.intracellulartherapies.com/clinical-development-pipeline/)