Informations générales (source: ClinicalTrials.gov)
A Randomized Double-blind Placebo-controlled Multicentre Study to Assess Safety, Tolerability, Pharmacokinetics and Efficacy of Radotinib in Parkinson's Disease
Interventional
Phase 2
Il-Yang Pharm. Co., Ltd. (Voir sur ClinicalTrials)
septembre 2021
décembre 2026
17 juillet 2024
This is a safety, tolerability, pharmacokinetic and efficacy study in subjects with
Parkinson's disease
Etablissements
Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
---|---|---|---|---|---|
CHU de Lyon HCL - Lyon - France | Stephane THOBOIS | Contact (sur clinicalTrials) | |||
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
CHRU de Lille - Hôpital Roger Salengro - Lille - France | Luc DEFEBVRE | Contact (sur clinicalTrials) | |||
CHU de Rouen - Rouen - France | David MALTETE | Contact (sur clinicalTrials) | |||
Chu La Miletrie - Poitiers - France | Isabelle BEBATRU | Contact (sur clinicalTrials) | |||
CHU Limoges - Limoges - France | Philippe COURATIER | Contact (sur clinicalTrials) | |||
Hôpital Nantes-Hotel Dieu - Nantes - France | Damier Philippe | Contact (sur clinicalTrials) | |||
Hôpital Pitié-Salpêtrière - Paris - France | LOUISE LAURE MARIANI | Contact (sur clinicalTrials) |
Critères
Tous
Inclusion Criteria:
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 a 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.
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 a 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.
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 (MMSE ≤ 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 (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 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 (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 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.