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

NCT04691661 | Recruiting Phase 2 DMC

• 1 other identifier: RT51EP1902
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

This is a safety, tolerability, pharmacokinetic and efficacy study in subjects with Parkinson's disease

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Evaluation of safety parameters: Adverse Events

  Incidence and severity of treatment emergent AEs

  12 months after dose administration

Secondary Outcomes (13)

• Pharmacokinetics assessments of Radotinib HCl: Cmax

  14 days after dose administration

• Pharmacokinetics assessments of Radotinib HCl: Tmax

  14 days after dose administration

• Pharmacokinetics assessments of Radotinib HCl: Ctrough

  14 days after dose administration

• Pharmacokinetics assessments of Radotinib HCl: AUCt

  14 days after dose administration

• Pharmacokinetics assessments of Radotinib HCl: AUCinf

  14 days after dose administration

Other Outcomes (6)

• Brain DaT SPECT to measure dopamine neurons and nerve terminals

  12 months

• Concentration of α-synuclein in CSF

  6 months

• Concentration of Tau and phospho-Tau (p-181) in CSF

  6 months

Study Arms (2)

Placebo: Dose escalation

PLACEBO COMPARATOR

Forty (40) subject will be recruited and randomized into 4 dosing groups. In each dosing group, ten (10) will be randomized and 8 of 10 will receive the active product (Radotinib) and 2 subjects will receive the matching placebo orally once daily for 6 months at each escalating dose level.

Drug: Placebo

Radotinib HCl: Dose escalation

EXPERIMENTAL

Forty (40) subject will be recruited and randomized into 4 dosing groups. In each dosing group, ten (10) will be randomized and 8 of 10 will receive the active product (Radotinib) and 2 subjects will receive the matching placebo orally once daily for 6 months at each escalating dose level. The inclusion of subjects in the next dose level will be decided by the sponsor in consultation with a Data Monitoring Committee (DMC).

Drug: Radotinib HCl 50 mg

Interventions

Radotinib HCl 50 mg DRUG

Enrolled subject will continue to administer Radotinib 50mg/day, 100mg/day, 150mg/day, 200mg/day, depending on the dose level once daily for 6 months.

Also known as: Radotinib, IY5511

Radotinib HCl: Dose escalation

Placebo DRUG

Placebo

Placebo: Dose escalation

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and Female from 40 to 80 years old;
• 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;
• 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;
• Hoehn \& Yahr stage ≤ 2.5;
• Without previous symptomatic treatment for PD disease and with current clinical state not requiring started dopaminergic therapy within 6 months from Baseline;
• Absence of a parkinsonian syndrome and other neurovascular comorbidities, confirmed by MRI
• 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;
• Covered by Health Insurance System;
• Able to understand and to sign the informed consent prior to screening;
• Blood Pressure (BP) and Heart Rate (HR) considered NCS by Investigator;
• Electrocardiogram (ECG) recording on a 12-lead ECG considered NCS by Investigator;
• 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.

You may not qualify if:

• Atypical Parkinsonism or drug-induced Parkinsonism;
• 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.
• Prior use of dopaminergic therapy (e.g., levodopa, dopamine agonist, amantadine, rasagiline) for 30 or more days any time in the past;
• Cognitive impairment (MMSE ≤ 24);
• Severe or uncontrolled chronic disease;
• Significant medical history of congenital or acquired bleeding disorders;
• Treatment by Deep Brain Stimulation or continuous infusion of apomorphin/dopa gel;
• Any below impaired cardiac function:
• 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

Sponsors & Collaborators

• Il-Yang Pharm. Co., Ltd.: lead

Study Sites (7)

CHRU de Lille - Hôpital Roger Salengro

Lille, France

NOT YET RECRUITING

CHU Limoges

Limoges, France

RECRUITING

CHU de Lyon HCL

Lyon, France

RECRUITING

Hôpital Nantes-Hotel Dieu

Nantes, France

RECRUITING

Hôpital Pitié-Salpêtrière

Paris, France

RECRUITING

Chu La Miletrie

Poitiers, France

RECRUITING

CHU de Rouen

Rouen, France

RECRUITING

Related Publications (1)

• Joshi D, Kulkarni M, Parekh P, Shah S, Greig NH, Acharya S. Targeting protein kinases in Parkinson's disease: the emerging role of phytoconstituents. Nutr Neurosci. 2025 Dec;28(12):1532-1563. doi: 10.1080/1028415X.2025.2531356. Epub 2025 Jul 18.

  PMID: 40680102 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Interventions

4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Philippe DAMIER, Pr.

  CHU Nantes - Hôpital Nord Guillaume et René Laennec

  PRINCIPAL INVESTIGATOR

Central Study Contacts

IL-YANG CR

CONTACT

+82.70.7165.7316; nykim@ilyanga.co.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: December 31, 2020
• Study Start: September 9, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)