To Evaluate the Efficacy of CVN424 in Parkinson's Disease Participants With Motor Complications

Exclusion Criteria33

• Diagnosis of secondary or atypical parkinsonism.
• Severe or disabling dyskinesias or OFF expected to preclude successful study participation, in the opinion of the investigator.
• Any previous procedure or therapy designed to provide continuous levodopa or stimulation of dopaminergic tone (i.e., Duopa, apomorphine, subcutaneous levodopa), surgery for PD (i.e., deep brain stimulation \[DBS\]), or anticipation of these during the study.
• History of exclusively diphasic, OFF state, myoclonic or dystonic dyskinesias without peak-dose choreiform dyskinesia.
• Clinically significant orthostatic hypotension (consistently symptomatic or requires medication).
• Clinically significant hallucinations requiring antipsychotic use.
• Current use of strong CYP3A4/5 inhibitors or inducers.
• Routine use of PD on-demand medications (i.e., inhaled levodopa, apomorphine injection). Routine use defined as three (3) or more uses per week of on-demand medication is not allowed. On demand medications should only be used for medical emergencies and should be avoided on anticipated diary days, as best as possible.
• Use of injectable botulinum medication for sialorrhea within 90 days of screening or during the study.
• Current use of medication with dopamine antagonist activity, or any use within 12 months of Screening.
• Clinically significant medical, surgical, psychiatric, or laboratory abnormalities that in the judgment of the investigator would preclude adequate participation or completion of the study.
• Clinically significant ECG abnormalities at Screening.
• Prolonged Fridericia-corrected QT (QTcF) interval on ECG at Screening.
• Clinically significant heart disease within 2 years of Screening, defined as follows:
• Significant cardiac event within 12 weeks prior to Screening (e.g., admission for myocardial infarction, unstable angina, or decompensated heart failure), angina pectoris or episode of congestive heart failure with symptoms \> grade 2 New York Heart Association classification, or presence of cardiac disease that in the opinion of the investigator increases the risk of ventricular arrhythmia.
• History of complex arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment.
• Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
• Symptomatic bradycardia, sick sinus syndrome or atrioventricular block greater than first degree in the absence of a pacemaker
• Unexplained syncope
• Brugada syndrome
• Hypertrophic cardiomyopathy
• Any clinically significant history of malignancy or ongoing malignancy of sufficient concern for interference with completion of the study or quality of study experience, in the opinion of the investigator and medical monitor.
• Active major depressive disorder or a Beck Depression Inventory-II (BDI-II) score of \> 19.
• Has active suicidal ideation within one year prior to Screening as determined by the C-SSRS or attempted suicide within the last 5 years.
• Has been diagnosed with or history of a substance-related disorder (excluding nicotine and caffeine), including alcohol-related disorder by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria, during the 12 months prior to Screening.
• Tests positive at Screening for drugs of abuse. Drugs of abuse refers to illicit substances and does not include participants taking physician-prescribed medications. For participants who are legally prescribed cannabis for medical reasons, the appropriateness of the participant for this study will be made by the judgement of the Investigator in consultation with the Medical monitor.
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN) or a degree of hepatic impairment using the Child-Pugh classification of B or C.
• Significant renal impairment as determined by estimated glomerular filtration rate (eGFR) less than or equal to 60 milliliters per minute (ml/min).
• Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCV) antibody, or Human Immunodeficiency Virus (HIV) infection at Screening.
• Currently lactating or pregnant or planning to become pregnant during the study.
• Previous exposure to CVN424.
• Currently participating in or has participated in another study of an investigational medicinal product (IMP) or medical device in the last 3 months or within 5 half-lives of the IMP (whichever is longer) prior to Screening.
• A known hypersensitivity to the IMP or to any excipients used in the formulation.