A Multiple Ascending Dose Study With LY03003 in Patients With Early-stage Parkinson's Disease
A Multiple Ascending Dose Study With LY03003 in Patients With Early-stage Parkinson's Disease
This study is to evaluate the safety and tolerability and to characterize the
 pharmacokinetics of multiple ascending dose (MAD) of LY03003 following intramuscular
 injections.
Inclusion Criteria:

 1. Patient had Parkinson's Disease that meet the clinical diagnostic criteria of the
 brain bank of the Parkinson's Disease Association of the United Kingdom.

 2. Patient was Hoehn & Yahr stage ≤3 (excluding stage 0) ;

 3. Patient was male or female aged 18 to 75 years;

 4. Patient had a Mini Mental State Examination (MMSE) score of ≥25;

 5. Patient had a Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III)
 of ≥10 but ≤30 at Screening.

 6. Patient who signed the informed consent form volunteered to participate in this
 clinical trial and could cooperate with the prescribed inspections.

 Exclusion Criteria:

 1. Patient had atypical Parkinson's syndrome(s) due to drugs (e.g., metoclopramide,
 flunarizine), metabolic neurogenetic disorders (e.g., Wilson's disease), encephalitis,
 cerebrovascular disease, or degenerative disease (e.g., progressive supranuclear
 palsy);

 2. Patient had a history of pallidotomy, thalamotomy, deep brain stimulation, or fetal
 tissue transplant;

 3. Patient had dementia, schizophrenia or hallucinations, or clinically significant
 depression;

 4. Patient had a lifetime history of suicide attempt (including an active attempt,
 interrupted attempt, or aborted attempt), or presence of suicidal ideation in the past
 6 months as indicated by a positive response ("Yes") to either Question 4 or Question
 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening;

 5. Patient had a history of orthostatic hypotension with a decrease of ≥20 mmHg in
 systolic blood pressure (SBP) or ≥10 mmHg in diastolic blood pressure when changing
 from the supine to the standing position and keeping in the standing position for 3
 minutes;

 6. Patient had received therapy with a dopamine (DA) agonist either concurrently or had
 done so within 28 days prior to the Screening;

 7. Patient had received therapy with 1 of the following drugs either concurrently or
 within 28 days prior to Screening: monoamine oxidase B (MAO-B) inhibitors (e.g.,
 pargyline, selegiline), DA releasing agents (e.g., amphetamine), reserpine,
 DA-antagonists (e.g., metoclopramide), neuroleptics, or other medications that may
 interact with DA function;

 8. Patient was currently (at the time of Screening) receiving central nervous system
 active therapy (e.g., sedatives, hypnotics, antidepressants, anxiolytics), unless the
 dose had been stable for at least 28 days prior to Screening Visit and was likely to
 remain stable for the duration of the study;

 9. Patient had a current diagnosis of epilepsy, had a history of seizures as an adult
 within 1 year prior to Screening, had a history of stroke or transient ischemic attack
 within 3 months prior to Screening;

 10. Patient had a history of known intolerance/hypersensitivity to non-dopaminergic
 antiemetics, such as domperidone, ondansetron, tropisetron;

 11. Patient had clinically significant liver dysfunction (which defined as total bilirubin
 above the upper limit of normal range, or alanine transferase (ALT) and / or aspartate
 transferase (AST) 2 times higher than the upper limit of normal range);

 12. Patient had clinically significant renal insufficiency (serum creatinine >2.0 mg/dL [
 >178 μmol/L]);

 13. Patient had clinically significant cardiac insufficiency and/or had myocardial
 infarction in the past 12 months;

 14. Patient had a history of allergic to any medication;

 15. Heavy smoker, alcoholic, drug addict;

 16. Female patients who were pregnant or were breastfeeding or were of childbearing
 potential without adequate contraception; male patients who cannot take adequate
 contraception during the study;

 17. Patient who was inappropriate to participant in the study in the judgment of the
 Investigator.