A randomized, double-blind, placebo parallel-controlled Phase II clinical trial to evaluate the efficacy and safety of TJ0113 capsule in patients with early-stage Parkinson's disease

This study is a randomized, double-blind, placebo parallel-controlled phase II clinical trial which is designed to assess the efficacy and safety of TJ0113 capsules in the treatment of patients with early-stage Parkinson's disease (PD). It is planned to include approximately 150 subjects with early-stage PD who will be randomized in a 1: 1 ratio into two cohorts (Cohort 1: 200 mg dose group; Cohort 2: 400 mg dose group). Within each cohort, subjects who have been successfully screened will be randomly assigned to TJ0113 capsule group and the placebo group in a ratio of 2: 1 within each stratum based on a stratification factor whether they have been receiving levodopa, the background medication for PD (yes vs. no) at a stable dose. Among them, approximately 50 subjects will receive TJ0113 capsules and approximately 25 subjects will receive the placebo. In this study, there will be approximately 50 subjects in each of the TJ0113 capsules 200 mg group, TJ0113 capsules 400 mg group and the placebo group.

After randomization, subjects will receive the oral administration of TJ0113 capsules or the placebo for 12 consecutive weeks and continue to receive follow-up visits for 1 week after the end of treatment. For subjects who have been receiving the anti-PD drug at a stable dose for at least 4 weeks prior to study entry, the original regimen of the background medication for PD should be maintained during the study.

Inclusion Criteria:

1. Subjects who voluntarily participate in the clinical trial, and have signed the informed consent form (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;
2. Males or females aged 30-80 years (both inclusive) at the time of signing the ICF;
3. Subjects who are diagnosed with PD according to the Diagnostic Criteria for Parkinson's Disease in China (2016 edition);
4. The scores of modified Hoehn and Yahr Scale at screening are 1-2.5 (both inclusive);
5. Subjects who have not previously received anti-PD drugs; or those who have previously used any anti-PD drugs but have not received such drug within 4 weeks before study entry; or those who have received the anti-PD drug at a stable dose for at least 4 weeks before study entry and agree to maintain the original treatment regimen during the study;
6. Subjects with the scores of MDS-UPDRS Part III of ≥ 22 at screening (it should be scored ≥ 12 hours apart from the most recent dose of the anti-PD drug for subjects who have been receiving an anti-PD drug at a stable dose for at least 4 weeks prior to study entry);
7. Subjects of childbearing potential (including spouses of male subjects) 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:

1. 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;
2. Subjects 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;
3. Subjects with prior personal or family history of long-QT syndrome, family history of sudden death of any immediate family members (meaning a parent, child, or sibling) prior to the age of 40 years; and/or personal history of unexplained syncope within 1 year prior to screening; and/or QTcF > 450 ms (male), QTcF > 470 ms (female) measured by Electrocardiogram(ECG) at rest during screening;
4. Subjects 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);
5. Subjects 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);
6. Atypical PD (e.g., Parkinsonism, multiple system atrophy, progressive supranuclear palsy), or secondary PD (e.g., delayed or drug-induced PD);
7. Subjects 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;
8. Subjects who have clinically significant renal insufficiency (creatinine clearance [Ccr] < 30 mL/min, see the calculation formula in Appendix II);
9. Any condition (e.g., severe arthritis, severe dyskinesia, traumatic injury with permanent physical disability) that may affect the MDS-UPDRS motor examination;
10. Subjects 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;
11. Subjects who suffer from severe mental abnormalities (anxiety, depression) as judged by the investigator, and the depression or anxiety score as rated by the Part I of the MDS-UPDRS is ≥ 3 at screening;
12. Subjects who have taken any serotonin reuptake inhibitors (such as fluoxetine, paroxetine, trazodone, citalopram, escitalopram, etc.) within 4 weeks prior to screening;
13. Subjects who have dementia or moderate or above cognitive dysfunction and the MDS-UPDRS score for 1.1 cognitive impairment is ≥ 3 at screening;
14. Subjects 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 subject safety or study results as judged by the investigator) during the study;
15. Subjects 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;
16. Subjects with evidence of alcoholism (≥ 14 units of alcohol per week on average, 1 unit ≈ 360 mL of beer, 45 mL of liquor, or 150 mL of wine) or drug abuse within 6 months prior to screening that may interfere with the subject's understanding of the study or completion of the study as judged by the investigator;
17. Subjects who are known to have hypersensitivity/allergic reaction or intolerance to any component of the investigational product;
18. Positive for any of the hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, and Treponema pallidum antibody (TP-Ab) at screening;
19. Pregnant or breastfeeding women;
20. Subjects 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 subjects participating in the study, as judged by the investigator;
21. Subjects who have a history of organ transplantation (excluding corneal transplantation);
22. Subjects who have donated or lost blood of ≥400 mL, or received blood transfusions within 3 months prior to screening;
23. Subjects 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.

AEs are collected in this trial from the time the subject receives the investigational product (i.e., TJ0113 capsules or placebo) until the end of the follow-up period.(From enrollment to end of treatment at 13 weeks.)