Safety, Tolerability, Pharmacokinetics and Efficacy Study of Radotinib in Parkinson's Disease

Inclusion Criteria:

1. Male and Female from 40 to 80 years old;

2. Diagnosed with "Clinically Probable Parkinson's Disease" according to the MDSclinical diagnostic criteria, with documented onset of symptoms per treatingphysician's records within three years of the screening visit;

3. Positive DAT-scan (e.g. a striatal dopamine transporter deficit on dopaminetransporter imaging by DaT-SPECT, characterized by crescent-shaped areas ofasymmetrical aspect, or of symmetrical aspect but of uneven intensity, between theright and the left brain hemisphere) confirmed by local reading;

4. Hoehn & Yahr stage ≤ 2.5;

5. Without previous symptomatic treatment for PD disease and with current clinicalstate not requiring started dopaminergic therapy within 6 months from Baseline;

6. Absence of a parkinsonian syndrome and other neurovascular comorbidities, confirmedby MRI

7. Female subjects must be not of childbearing potential, e.g., documented evidencethat they are surgically sterile (e.g., hysterectomy, partial hysterectomy,bilateral oophorectomy, bilateral tubal ligation), or postmenopausal (at least 12months since last menses) or using highly effective method of birth control definedas those which result in a low failure rate (i.e. less than 1% per year) when usedconsistently and correctly, such as combined hormonal contraception associated withinhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonalcontraception associated with inhibition of ovulation (oral, injectable,implantable), intra uterine devices (IUDs), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, condom, until at least one month after the lastdrug intake associated to a negative pregnancy test at screening;

8. Covered by Health Insurance System;

9. Able to understand and to sign the informed consent prior to screening;

10. Blood Pressure (BP) and Heart Rate (HR) considered NCS by Investigator;

11. Electrocardiogram (ECG) recording on a 12-lead ECG considered NCS by Investigator;

12. Laboratory parameters within the normal range of the laboratory. Individual valuesout of the normal range can be accepted if judged clinically non relevant by theInvestigator.

Exclusion Criteria:

1. Atypical Parkinsonism or drug-induced Parkinsonism;

2. Current, or within 60 days of screening, use of any prescription, investigational,or over the counter medication for the symptomatic treatment of PD or to slow theprogression of PD.

3. Prior use of dopaminergic therapy (e.g., levodopa, dopamine agonist, amantadine,rasagiline) for 30 or more days any time in the past;

4. Cognitive impairment (MMSE ≤ 24);

5. Active psychiatric disorder (mood disorders, hallucinations or delirium with strongfunctional impact and not controlled by medication or which happened during the last 3 months before inclusion);

6. Severe or uncontrolled chronic disease;

7. Significant medical history of congenital or acquired bleeding disorders;

8. Treatment by Deep Brain Stimulation or continuous infusion of apomorphin/dopa gel;

9. Any below impaired cardiac function:

• LVEF <45% or < lower bound of normal limit of study site (whichever higher),confirmed by echocardiogram (if the subject has already carried out thisexamination during the last month before inclusion, he/she will be exemptedfrom retaking this examination, but he/she will have to present theechocardiogram as well as the cardiologist's report. If not, this exam shouldbe performed during the screening period)

• Subjects who cannot have QT intervals measured according to ECG

• Complete left bundle branch block

• Subjects with cardiac pacemakers

• Subjects with congenital long QT syndrome or the family history of known longQT syndrome

• History of, or presence of symptomatic ventricular or atrial tachyarrhythmias

• Clinically significant resting bradycardia (< 50 bpm).

• Mean QTcF >450msec following three consecutive ECG tests at baseline: Screeningtest will be performed again for QTcF after the adjustment of electrolyte ifQTcF >450msec and the electrolyte is not within the normal range

• Medical history of clinically confirmed myocardial infarction

• Medical history of unstable angina (within last 12 months)

• Other clinically significant cardiac disease (e.g. congestive heart failure, oruncontrolled hypertension)

10. Participation in other investigational drug trials within 30 days prior toScreening;

11. Any concomitant medication or medication excluded that could put subject at risk, orinterfere with study evaluations;

12. Subjects currently receiving treatment with a strong CYP3A4 inhibitors (e.g.erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin,telithromycin, ritonavir, mibefradil) or strong CYP3A4 inducers (e.g. dexamethasone,phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbitol, St.John's Wort) or therapeutic Cumarin derivatives (e.g. warfarin, acenocoumarol,phenprocoumon) and that can neither stop the administration of these drugs beforethe start of the IP administration nor switch to other drugs

13. Subjects who are currently receiving treatment with a medication that has thepotential to extend QT intervals and can neither stop the administration of thedrugs before the start of the IP administration nor switch to other drugs (list ofmedications that have the potential to prolong QT interval is provided in theAppendix II) If subjects need to start such drug treatments during the study, thiswill be discussed with the sponsor, IL-YANG PHARM. Co., Ltd.

14. Subjects who are currently receiving treatment with P-gp inducers (e.g. (Ritonavir,Saquinavir, Nelfinavir, Indinavir, Amprenavir, Tipranavir...), Apalutamide, Estrone,Estriol, Trazodone, Vincristine, Tamoxifen, Doxorubicin, Carbamazepine,Oxcarbazepine, Fosphenytoin, Lorlatinib, Phenobarbital, Phenytoin, Propofol,beclomethasone, Dexamethasone, Prednisone, Hydrocortisone, Diclofenac, Rifampicin,Reserpine, Nifedipine, Digoxine, Amiodarone, Spironolactone, Levothyroxine,Tacrolimus, Sirolimus, St. John's Wort (herbal ingredient)) and that can neitherstop the administration of these drugs before the start of the IP administration norswitch to other drugs;

15. Gastrointestinal disorder or gastrointestinal disease that may result in asignificant change in the absorption of the investigational product;

16. Medical history of acute or chronic pancreatitis within the past one year;

17. Acute or chronic liver, pancreas, or severe kidney disease that are not associatedwith the disease;

18. Subjects known seropositive to human immunodeficiency virus (HIV), current acute orchronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, orcirrhosis. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stablehepatitis B (HBV DNA < 500 IU/mL or site specific local lab normal range lower limitassessed by investigator), and cured hepatitis C subjects can be enrolled;

19. Men subjects who are unwilling to use and appropriate method of contraception duringthe study;

20. Subjects who have hypersensitivity to active ingredient or any of the excipients ofthis investigational product;

21. Any medical condition that might interfere with the protocol except those defined inSection 5.3 of the study protocol;

22. Subject unable to attend scheduled visits or to comply to the protocol;

23. Subject under legal guardianship or judicial protection;

24. Subject in the exclusion period of another protocol;

25. No possibility of contact in case of emergency.