VG081821AC Tablets for Early to Mid-stage Parkinson's Disease

Inclusion criteria

• Male or female aged 18 ≤ Age ≤ 80 at the time of signing the informed consent.
• Diagnosed with Parkinson's disease per the Chinese Diagnostic Criteria for Parkinson's Disease (2016 Edition), and time from initial diagnosis ≤ 7 years.
• Modified Hoehn-Yahr scale rated as 1~3 (inclusive) at screening.
• MDS-UPDRS Part III score ≥ 22 at screening.
• Have not taken anti-Parkinson drugs containing levodopa within 4 weeks prior to screening [see main text section 5.7.1] (Note: Patients who have previously taken levodopa-containing anti-Parkinson drugs can participate in this trial after a 4-week washout period).
• Patients receiving amantadine and/or anticholinergic drugs prior to screening must have been on a stable treatment regimen for at least 4 weeks prior to screening, and the dose must not change during the study.
• Women of childbearing potential must have a negative pregnancy test result at screening, and the participant must agree to use approved contraceptive measures throughout the study period.
• Must provide written informed consent and be willing and able to comply with the trial protocol (e.g., able to understand and complete questionnaires, follow the visit schedule, and use the medication).

Exclusion criteria

• Presence of any medical condition that may interfere with full participation in the study, including but not limited to the following: current diagnosis of active epilepsy; history of hemolytic anemia, pulmonary embolism, respiratory depression, dementia, active psychiatric disease, severe depression, or malignant tumor.
• History of congestive heart failure (New York Heart Association functional class 3 or 4) or known left ventricular ejection fraction <30%.
• History of angina pectoris, myocardial infarction, cerebrovascular accident, percutaneous coronary intervention, peripheral arterial bypass surgery, transient ischemic attack (TIA), or stroke within 3 months prior to screening.
• History of arrhythmia or presence of uncontrolled arrhythmia, including but not limited to: atrial fibrillation, Wolff-Parkinson-White syndrome, congenital long QT syndrome, and ECG indicating QTc interval prolongation (defined as male (QTc) > 450 ms, female (QTc) > 470 ms); [Fridericia formula: QTc=QT/(RR^0.33), where RR represents the standard heart rate value, calculated by dividing 60 by the heart rate].
• Use of dopamine receptor agonists, monoamine oxidase inhibitors, catechol-O-methyltransferase (COMT) inhibitors, adenosine A2A receptor antagonists, or drugs with dopamine receptor antagonist effects within 4 weeks prior to screening [see main text section 5.7.1]. (Note: For newly diagnosed patients undergoing an acute dopaminergic challenge test-i.e., taking a single dose of levodopa [e.g., Madopar] or dopamine agonist [e.g., Apomorphine]-they can be enrolled after a 3-day washout period).
• History of drug or other allergies where the investigator considers participation in this study to be of high risk, or previous allergic reactions to adenosine A2A receptor antagonists, or suspected by the investigator to be allergic to the study drug or any of its components.
• Plan to take drugs that are inhibitors or inducers of efflux transporters (P-gp, BCRP) during the study period.
• Suffering from uncontrolled hypertension (treated or untreated) at screening, defined as systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg. (Note: After establishing good blood pressure control within a reasonable timeframe, the investigator may permit re-measuring of blood pressure up to the baseline visit, at their discretion).
• Presence of clinically significant hepatic impairment (defined as total bilirubin and/or direct bilirubin, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) above the upper limit of the reference range, and deemed clinically significant by the investigator).
• Presence of any of the following: positive Hepatitis B surface antigen; positive Hepatitis C virus antibody; positive Hepatitis E virus antibody; positive Human Immunodeficiency Virus (HIV) test; positive Treponema pallidum test.
• Previous non-response to high-dose levodopa (excluding cases of malabsorption) or previous non-response to adequate dopaminergic therapy.
• Presence of clinically significant renal impairment (creatinine clearance Ccr <30mL/min), calculated at screening using the Cockcroft-Gault formula: Ccr (mL/min) = (140 - Age) × Weight (kg) / [72 × Serum Creatinine (SCr) (mg/dL)] (Female × 0.85) or Ccr (mL/min) = (140 - Age) × Weight (kg) / [0.814 × Serum Creatinine (SCr) (μmol/L)] (Female × 0.85).
• Investigator judges the participant to be at risk for suicide, or if the participant answers "yes" to Question 4 and/or Question 5 of the Suicidal Ideation subscale, or any question on the Suicidal Behavior subscale of the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening.
• Investigator judges the participant to have severe psychiatric abnormalities (anxiety, depression), with a Hamilton Depression Rating Scale-17 (HAMD-17) score >23, or a Hamilton Anxiety Rating Scale (HAMA) score >21 at screening.
• Participant has significant cognitive impairment or dementia, including the following scenarios: Illiterate participants (uneducated) with an MMSE score ≤19 at screening; Primary school participants (education ≤6 years) with an MMSE score ≤22 at screening; Middle school and above participants (education >6 years) with an MMSE score ≤23 at screening.
• History of surgical treatment for Parkinson's disease.
• Use of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, biofeedback therapy, acupuncture, traditional Chinese medicine, and other traditional rehabilitation methods within 4 weeks prior to screening (Note: Patients can participate in this trial after a 4-week washout period).
• History of heavy alcohol consumption for more than 3 consecutive months within 1 year prior to screening, defined as: female participants drinking an average of >20 g of alcohol daily (calculated as pure alcohol; 20 g is roughly equivalent to two 300 mL glasses of beer, 40 mL of spirits, or 140 mL of wine), and male participants drinking an average of >30 g of alcohol daily (calculated as pure alcohol; 30 g is roughly equivalent to three 300 mL glasses of beer, 60 mL of spirits, or 210 mL of wine), or inability to reliably quantify alcohol consumption according to the investigator's judgment.
• History of excessive tea and/or coffee consumption within the past 4 weeks, or anticipated excessive consumption during the clinical trial period. (Excessive tea consumption is defined as 4 or more cups a day, 1 cup = 250 mL; second or third steepings without adding new leaves still count as 1 cup total, not two or three. Excessive coffee consumption is defined as 2 or more cups a day, 1 cup = 250 mL; for participants who do not drink coffee every day, 2 cups per day is permissible for one day a week, but no more than 2 cups; and the defined consumption limit must not be exceeded throughout the entire trial).
• Active substance abuse (including inhaled or injected drugs) within 1 year prior to screening.
• Participated in another drug clinical trial (meaning received investigational drug treatment) within 3 months prior to randomization.
• Any other condition where the investigator considers the participant unsuitable for this study.