This grant builds upon the research from a prior grant: Safety, Tolerability and Efficacy of ADX48621 in the Treatment of Levodopa-induced Dyskinesia in Parkinson's Disease
Study Rationale:
Dipraglurant is a modulator of the metabotropic glutamate receptor 5 (mGluR5). Blockade of this receptor has been shown to have anti-parkinsonian and anti-dyskinetic effects in a variety of pre-clinical models. Dipraglurant, in particular, has shown significant effects in reducing dyskinesia in a pre-clinical model of Parkinson’s disease levodopa-induced dyskinesia (PD-LID). This study will determine what dose of dipraglurant should be used in a Phase IIB study for PD-LID.
Hypothesis:
We will learn how efficiently dipraglurant binds to mGluR5 and how much of the drug is available in the body to reach mGluR5.We will also learn more about the differences between the immediate-release and extended-release forms of dipraglurant.
Study Design:
To understand how dipraglurant binds to mGluR5, we will study the dose-dependent binding of the compound using positron emission tomography (PET) in healthy subjects. We will also investigate the absolute bioavailability, absorption, distribution, metabolism and excretion of the compound after administration of the immediate and extended release forms of dipraglurant and will evaluate the influence of the individual metabolic profile of each subject on the rate of metabolism.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The advancement of a therapeutic option for PD-LID could lead to increased use of levodopa as well as the management of dyskinesia-specific symptoms.
Next Steps for Development:
The results of these studies will provide insight for the Phase 2B study design. Specifically, the PET study is expected to demonstrate the efficiency of dipraglurant binding to mGluR5 as plasma concentration of the compound is increased. The clinical study is expected to help us understand the absolute availability of dipraglurant to interact with mGluR5. These data will be critical to rapidly moving the program into Phase IIB and Phase III studies and ultimately approval of the compound.