Please refer to the full title.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Il-Yang Pharm Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

12 Apr 2021 → ongoing

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

IL-YANG PHARM. Co., Ltd.

External identifiers

EU CT number

2024-516549-37-00

EudraCT number

2019-004268-23

ClinicalTrials.gov

NCT04691661

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Therapy

To evaluate the safety and tolerability of Radotinib (50, 100, 150 and 200 mg), administered during 6 months, compared to placebo, in Parkinson's disease subjects.

Secondary objectives 5

1. To evaluate the pharmacokinetics parameters of Radotinib after daily oral administration at 4 different doses in Parkinson's disease subjects.
2. To evaluate the efficacy of Radotinib (50, 100, 150 and 200 mg), administrated during 6 months, compared to placebo, on severity of motor symptoms in Parkinson's disease subjects, based on non-progression of MDS-UPDRS scale assessment.
3. To evaluate the effect of Radotinib (50, 100, 150 and 200 mg), in the needed time from baseline to the initiation of dopamine-replacement medication, compared to placebo.
4. To evaluate the effect of Radotinib (50, 100, 150 and 200 mg) on quality of life compared to placebo.
5. To evaluate the effect of Radotinib (50, 100, 150 and 200 mg) on clinical global impression of change.

Conditions and MedDRA coding

Treatment of Parkinson’s disease (PD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male and Female from 40 to 80 years old
2. Diagnosed with "Clinically Probable Parkinson's disease" according to the MDS clinical diagnostic criteria, with documented onset of symptoms per treating physician's records within three years of the Screening visit
3. Positive DAT-scan (e.g. a striatal dopamine transporter deficit on dopamine transporter imaging by DaT-SPECT, characterized by crescent-shaped areas of asymmetrical aspect, or of symmetrical aspect but of uneven intensity, between the right 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 clinical state not requiring started dopaminergic therapy within 6 months from Baseline
6. Absence of another cause than Parkinson disease of the parkinsonian syndrome and other neurovascular comorbidities, confirmed by MRI
7. Female subjects must be not of childbearing potential, e.g., documented evidence that they are surgically sterile (e.g., hysterectomy, partial hysterectomy, bilateral oophorectomy, bilateral tubal ligation), or postmenopausal (at least 12 months since last menses) or using highly effective method of birth control defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception 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 last drug 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 values out of the normal range can be accepted if judged clinically non relevant by the Investigator

Exclusion criteria 25

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 the progression 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 (Mini Mental State Examination ≤ 24)
5. Active psychiatric disorder (mood disorders, hallucinations or delirium with strong functional 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 this examination during the last month before inclusion, he/she will be exempted from retaking this examination, but he/she will have to present the echocardiogram as well as the cardiologist's report. If not, this exam should be 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 long QT 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: Screening test will be performed again for QTcF after the adjustment of electrolyte if QTcF >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, or uncontrolled hypertension)
10. Participation in other investigational drug trials within 30 days prior to Screening
11. Any concomitant medication or medication excluded that could put subject at risk, or interfere with study evaluations
12. Subjects currently receiving treatment with a strong CYP3A4 inhibitors or strong CYP3A4 inducers or therapeutic Cumarin derivatives and that can neither stop the administration of these drugs before the start of the IP administration nor switch to other drugs
13. Subjects who are currently receiving treatment with a medication that has the potential to extend QT intervals and can neither stop the administration of the drugs before the start of the IP administration nor switch to other drugs (list of medications that have the potential to prolong QT interval is provided in the Appendix II). If subjects need to start such drug treatments during the study, this will be discussed with the sponsor, IL-YANG PHARM. Co., Ltd.
14. Subjects who are currently receiving treatment with P-gp inducers and that can neither stop the administration of these drugs before the start of the IP administration nor switch to other drugs
15. Gastrointestinal disorder or gastrointestinal disease that may result in a significant 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 associated with the disease
18. Subjects known seropositive to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, or cirrhosis. Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B (HBV DNA < 500 IU/mL or site specific local lab normal range lower limit assessed by investigator), and cured hepatitis C subjects can be enrolled
19. Men subjects who are unwilling to use and appropriate method of contraception during the study
20. Subjects who have hypersensitivity to active ingredient or any of the excipients of this investigational product
21. Any medical condition that might interfere with the protocol except those defined in Section 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluation of safety parameters (AE, vital signs, 12-lead ECG, laboratory parameters, physical exams).

Secondary endpoints 5

1. Pharmacokinetics assessments of Radotinib HCl: Cmax, Tmax, Ctrough, AUCt, AUCinf, AUC0-12h, Kel, t1/2, %AUCextra, Vd/F, CL/F, R.
2. Change from Baseline in the sum of MDS-UPDRS Parts I, II and III after 24 weeks of treatment.
3. Time from baseline to initiation of dopamine-replacement medication.
4. Change in health related quality of life as measured by a quality of life questionnaire (PDQ-39).
5. Subject's clinical global impression of change.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Il-Yang Pharm Co. Ltd.

Sponsor organisation

Il-Yang Pharm Co. Ltd.

Address

110 Hagal-Ro, Giheung-Gu Giheung-Gu

City

Yongin-Si

Postcode

17096

Country

Korea, Republic of

Scientific contact point

Organisation

Il-Yang Pharm Co. Ltd.

Contact name

Martin Giblin

Public contact point

Organisation

Il-Yang Pharm Co. Ltd.

Contact name

Martin Giblin

Third parties 3

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications