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

This is a randomized, double-blind, placebo-controlled, multicenter study in participants with Parkinson's disease (PD) with motor fluctuations. Participants will be randomized to receive once-daily oral doses of either 75 milligrams (mg) CVN424, 150 mg CVN424, or a matching placebo for 12 weeks. Participants who successfully complete this study and retain eligibility/suitability will be invited to participate in a future open-label extension (OLE) study.


Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of PD consistent with United Kingdom (UK) Brain Bank criteria and MDS Research Criteria for the Diagnosis of PD; must include bradykinesia with sequence effect and motor asymmetry if no rest tremor, and a prominent response to levodopa.
* Body Mass Index (BMI) \> 18.0 and \< 35.0 Kilograms per meter square (kg/m\^2), inclusive at Screening.
* Modified Hoehn and Yahr Stage ≤ 3 in the ON state.
* Freely ambulatory at the time of Screening (with/without assistive device).
* Montreal Cognitive Assessment (MoCA)7 Score of at least 24.
* PD medications must be stable for at least 4 weeks prior to Screening; monoamine oxidase B (MAO-B) inhibitors must be stable for at least 12 weeks prior to Screening.
* Levodopa administration at least 4 times daily (immediate or extended release) or three times daily (Rytary).
* Stable use of oral anti-sialorrhea medications for 30 days before Screening, without anticipated need for change during the study.
* Average of ≥ 3 h total OFF time/day on Screening home diaries, with at least 2.5 hours OFF on each diary day.
* During Screening, capable of adequately identifying ON, OFF, and dyskinetic states (\>80% concordance with a blinded rater) through properly completed ON/OFF diaries.
* Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and for at least 12 weeks after the last dose of study drug has been taken.
* Able and willing to give written informed consent approved by an institutional review board, and to comply with scheduled visits, treatment plan, laboratory tests, and other study-related procedures.
* Approved as an appropriate and suitable candidate by the Enrollment Authorization Committee (EAC)

Exclusion Criteria:

* 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), 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)
* 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 (opiates, tetrahydrocannabinol \[THC\], methadone, cocaine, and amphetamines \[including ecstasy\]).
* Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN).
* Significant renal impairment as determined by estimated glomerular filtration rate (eGFR) less than or equal to 55 millilitres 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.