SAD Study in Patients With Parkinson's Disease and Motor Fluctuations

Exclusion Criteria

• •1. Diagnosis of secondary or atypical parkinsonism
• •2. Any previous procedure or therapy designed to provide continuous levodopa or stimulation of dopaminergic tone (i.e., Duopa, apomorphine), surgery for PD (i.e., DBS), or anticipation of these during the study
• •3. History of exclusively diphasic, OFF state, myoclonic or dystonic dyskinesias without peak-dose choreiform dyskinesia
• •4. Clinically debilitating motor complications as determined by the principal investigator or delegate (severe, disabling dyskinesias or severe OFF)
• •5. Participant inability to differentiate motor states (OFF/ON/ON with mild/moderate/severe dyskinesias) after training
• •6. Clinically significant orthostatic hypotension (consistently symptomatic or requires medication)
• •7. Clinically significant hallucinations requiring antipsychotic use
• •8. Clinically significant medical, surgical, psychiatric, or laboratory abnormalities that in the judgment of the principal investigator or delegate would preclude adequate participation or completion of the study
• •9. Clinically significant ECG abnormalities at Screening
• •10. Prolonged Fridericia-corrected QT (QTcF) interval on ECG at Screening (defined as a QTcF interval of \>450 msec for males and 470 for females)
• •11. Clinically significant heart disease within 2 years of Screening, defined as follows:
• •A. 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 B. History of complex arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment (Common Terminology Criteria for Adverse Events grade 3) C. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia D. Symptomatic bradycardia, sick sinus syndrome or atrioventricular block greater than first degree in the absence of a pacemaker E. Unexplained syncope F. Brugada syndrome G. Hypertrophic cardiomyopathy
• •12. Active major depressive disorder or history of clinically significant impulse control disorder, in the opinion of the Principal Investigator or delegate, or EAC.
• •Note: Participants receiving treatment for depression with antidepressants may be enrolled if they have been on a stable daily dose of the antidepressant for at least 8 weeks prior to Screening.
• •13. Has active suicidal ideation within one year prior to Screening as determined by the C-SSRS (answer of "yes" on questions 4 or 5) or attempted suicide within the last 5 years
• •14. Has been diagnosed with or history of a substance-related disorder (excluding nicotine and caffeine), including alcohol-related disorder by DSM-V criteria, during the 12 months prior to Screening
• •15. Tests positive at Screening for drugs of abuse (amphetamines (AMP), barbiturates (BAR), benzodiazepines (BZO), cocaine (COC), opiates (OPI), methamphetamines (MET), methadone (MTD), Phencyclidine (PCP), tetrahydrocannabinol (THC), tricyclic antidepressants (TCA)) Note: does not exclude patients on physician-prescribed medications.
• •16. Has ALT or AST levels greater than 2.5 times the ULN or bilirubin \> 2.0 mg/dL, or \> 34.2 µmol/L
• •17. Significant renal impairment as determined by eGFR, using Cockcroft-Gault method, less than or equal to 55 ml/min or serum creatinine \>2.0 mg/dL or \>177 µmol/L
• •18. Has a positive test result for HBsAg, HCV antibody, or HIV infection at Screening
• •19. Currently lactating or pregnant or planning to become pregnant during the study.
• •20. Previous intolerance of apomorphine
• •21. Currently participating in or has participated in another investigational study within the last 30 days or 5 half-lives, or 90 days for biologics