Phase Ⅲ Clinical Trial to Evaluate the Efficacy and Safety of TJ0113 Capsules in Patients With Early-Onset Parkinson's Disease

Inclusion criteria

• Participants who voluntarily participate in the clinical trial, and have signed the ICF, are able to understand and follow the study protocol, willing to visit the study site on time, fully understand the content, process and potential adverse reactions of the study, and indicate the date of signing the ICF;
• Male or female aged 18 to 80 years (inclusive) at the time of signing the ICF;
• Meets the 2015 International Parkinson and Movement Disorder Society (MDS) diagnostic criteria for primary PD[1] or the 2016 Chinese diagnostic criteria for Parkinson's disease[13]; with an age of onset ≤50 years, diagnosed as EOPD;
• Able to cooperate in completing the "off" time records in the diary card;
• Modified Hoehn-Yahr stage 1~2.5 (inclusive) in the "off" state at screening;
• Has been stably receiving anti-PD treatment before baseline and agrees to keep the original anti-PD medication unchanged during the trial; at the time of randomization, the investigator judges that the current treatment regimen has achieved optimal disease management status;

-"Stably receiving anti-PD treatment" is defined as: 1) Must use levodopa, may be combined with other anti-PD medications; 2) The type and name of anti-PD medications used by the participant have remained unchanged for at least 3 months prior to the baseline visit, and the dose has remained unchanged for at least 1 month prior to the baseline visit; 3) In this trial: No planned dose regimen adjustments during the double-blind treatment period; changes to the dose of stably received anti-PD medications are discouraged during the open-label treatment period, but if necessary, the dose may be adjusted at the discretion of the investigator.

• MDS-UPDRS Part III score ≥22 in off-anti-PD medication state at screening;
• Participants of childbearing potential (including spouses of male participants) who have no childbearing or sperm donation plan from the end of the screening period to within 6 months after the last dose and are willing to use at least one effective method (see Appendix I for details) for contraception.

Exclusion criteria

• Presence of any medical condition that may interfere with full participation in the study, including but not limited to the following: medical history of epilepsy or any complications, medical history of hemolytic anemia, pulmonary embolism, respiratory depression, active psychiatric disease, or malignancy; positive tumor marker detection results at screening and judged by the investigator to be clinically significant;
• Participants who have experienced a New York Heart Association (NYHA) Class III or above congestive heart failure, unstable angina pectoris, acute myocardial infarction, hemorrhagic stroke (stroke), and ischemic stroke (including transient ischemic attack) within 6 months before screening; or those who have undergone any percutaneous coronary intervention or coronary artery bypass grafting, heart valve repair/replacement; or those with severe arrhythmia as judged by the investigator at the time of screening;
• A personal or family history of long QT syndrome, a family history of sudden death in first-degree relatives (parents, offspring, and siblings) before the age of 40; and/or a personal history of unexplained syncope within 1 year prior to screening; and/or QTcF >450 ms (male) or QTcF >470 ms (female) based on resting ECG results at screening;
• Participants with unstably controlled hypertension at screening, defined as the systolic blood pressure ≥ 160 mmHg and/or the diastolic blood pressure ≥ 100 mmHg (verify before randomization);
• Participants with symptomatic orthostatic hypotension at screening, or who experiences a decrease in systolic blood pressure of ≥ 30 mmHg or a decrease in diastolic blood pressure of ≥ 15 mmHg within 3 minutes when changing from the supine to the standing position (verify before randomization);
• Atypical Parkinsonism (e.g., multiple system atrophy, progressive supranuclear palsy, etc.), or secondary parkinsonism with clear etiologies such as drug-induced, vascular, toxic, metabolic, infectious, or traumatic brain injury;
• Participants who have clinically significant hepatic insufficiency which is defined as the total bilirubin (TBIL) > 2 × upper limit of normal (ULN) or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 × ULN;
• Participants with clinically significant renal insufficiency (creatinine clearance [Ccr] <30 mL/min, see Appendix 2 calculation formula);
• Any condition (e.g., severe arthritis, severe dyskinesia, traumatic injury with permanent physical disability) that may affect the MDS-UPDRS motor examination;
• Participants who have a history of suicidal intention (including actual attempts, interrupted attempts, or failed attempts) and are at risk of committing suicide as judged by the investigator;
• Participants judged by the investigator to have severe psychiatric abnormalities (anxiety, depression), with a single item score ≥3 for item 1.3 (Depression) or item 1.4 (Anxiety) in Part 1 of the MDS-UPDRS at screening;
• Participants who have taken any serotonin reuptake inhibitors (such as fluoxetine, paroxetine, trazodone, citalopram, escitalopram, etc.) within 4 weeks prior to screening;
• Use of anticholinergics or amantadine for PD treatment within 3 months prior to screening, or requiring stable use of anticholinergics or amantadine for PD treatment during the trial;
• Participants who have dementia or moderate or above cognitive dysfunction and the MDS-UPDRS score for 1.1 cognitive impairment is ≥ 3 at screening;
• Participants who have a history of surgical treatment for PD (e.g., deep brain stimulation, pallidotomy, etc.), or those who have undergone any major or medium surgery or have experienced any serious trauma or serious infection within 3 months prior to screening, those who are unsuitable for this study at the discretion of the investigator or plan to undergo any surgical treatment (excluding an outpatient surgery that has no impact on participant safety or study results as judged by the investigator) during the study;
• Participants who have participated in a clinical trial that involves the administration of an investigational drug (a new chemical entity), device, or surgery within 3 months or 5 half-lives before screening, whichever is longer;
• Evidence of alcohol abuse (average weekly consumption of ≥14 units of alcohol, where 1 unit ≈ 360 mL of beer, 45 mL of spirits, or 150 mL of wine) or drug abuse within 6 months prior to screening, which in the investigator's opinion would interfere with the participant's understanding or completion of the trial;
• Participants who are known to have hypersensitivity/allergic reaction or intolerance to any component of the investigational product;
• Positive for Hepatitis B surface antigen (HBsAg) or positive for Hepatitis B core antibody (HBcAb) with Hepatitis B Virus Deoxyribonucleic Acid (HBV-DNA) above the upper limit of detection, or positive for Hepatitis C Virus (HCV) antibody, or positive for Human Immunodeficiency Virus (HIV) antibody, or positive for Treponema pallidum antibody at screening;
• Pregnant or breastfeeding women;
• Participants who are unable to swallow oral drugs, or have any condition that may significantly affect the absorption, distribution, metabolism and excretion of the drug, or any condition that may pose a hazard to participants participating in the study, as judged by the investigator;
• Participants who have a history of organ transplantation (excluding corneal transplantation);
• Participants who have donated or lost blood of ≥400 mL, or received blood transfusions within 3 months prior to screening; Participants who have any other conditions that may affect study compliance as deemed by the investigator, or those who are unable to participate in the study for their own reasons.