Levodopa-induced dyskinesia in Parkinson's Disease
Conditions
Sponsors
Celon Pharma S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated, written informed consent before any study-specific procedures. 2. Patient has a diagnosis of clinically probable or definitive, idiopathic Parkinson’s disease, according to the United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria. 3. Patient has to be on L-dopa treatment for at least 3 years prior to Screening. 4. Patient must be on a stable dose of L-dopa with aromatic L-amino acid decarboxylase (AADC) inhibitors for at least 28 days before Screening. Patient might get additional catechol-O-methyltransferase (COMT) inhibitors on a stable dose. 5. The total cumulated optimized daily dose of L-dopa should be between 300 to 1600 mg divided into a minimum of 3 doses for at least 28 days before Screening. The L-dopa formulation may include immediate and extended-release forms. 6. In case a patient is on concomitant antiparkinsonian drugs, these concomitant drug doses should be optimized and stable i.e. dopamine agonists treating Parkinson’s disease-related motor and non-motor symptoms for at least 28 days before Screening. 7. Patient has been treated with L-dopa and is suffering from temporally predictable peak-dose LID. The patient should have mild to moderate LID specifically predictable peak-dose dyskinesia (at least two 30-minute intervals of ON time with troublesome dyskinesia between the hours of 09:00 am to 06:00 pm, at least 2 days during the period of Baseline hospitalization (within Days -3 to -1), documented in a Hauser Subject Diary). 8. Patient must consider the dyskinesia to be problematic or disabling for at least 3 months prior to Screening. 9. Score of dyskinesia is at least 2 on part IV, item 4.2 (functional impact of dyskinesia) of the MDS-UPDRS at Screening and on Day -1. 10. Patient with Hoehn-Yahr stages 2 to 4 (in OFF stage). 11. Male or female patient aged 50 to 80 years, inclusive, at Screening. 12. Female patient is eligible to participate if she is not pregnant (negative pregnancy test at Screening and Day -1), not breastfeeding and at least 1 of the following conditions applies: Woman of non childbearing potential. Woman of childbearing potential, who agrees to use contraceptive methods during the Treatment Period and for at least 28 days after the last dose of the study drug. (The following are acceptable contraceptive methods: bilateral tubal occlusion, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and copper intrauterine devices, male or female condom with spermicide; and cap, diaphragm or sponge with spermicide). 13. Male patient must agree to use a barrier method of contraceptive (condom + spermicide gel) for at least 90 days after the last dose of the study drug. 14. Patient agrees to blood sample collection for DNA analysis. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 43 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Patient has (suspected) atypical Parkinson’s disease. 2. Patient has a history of neurosurgical intervention because of Parkinson’s disease (e.g. deep brain stimulation [DBS]). 3. Transcranial magnetic stimulation was applied within 6 months prior to Screening. 4. Patient has a history of L-dopa or dopaminergic agonist therapy-induced psychotic event, impulse control disorder. 5. Patient has exclusively diphasic, off state, myoclonic, dystonic or akathetic dyskinesia or early morning dystonia without peak-dose dyskinesia. 6. The patient has any moderate or severe neuromuscular, locomotor disease (e.g., chronic, severe rheumatoid arthritis), which might interfere with the study scoring. 7. Patient has a history of severe head injury, stroke or any diagnosis of significant nervous system disease which, in the opinion of the Investigator can affect the patient cognition or motor function of any time. 8. Patient has positive urine drug results (illicit, illegal or without a valid prescription or medical need) at Screening and Baseline. 9. Patient has a history of substance abuse or alcohol abuse within 12 months prior to Screening. 10. If female, the patient is pregnant or lactating or intending to become pregnant (a positive pregnancy test at Screening or Day 1), or intending to donate ova, before or during the course of the study or within 12 weeks after final administration of IMP or placebo. 11. Patient has a history of or known personality disorder or other psychiatric disorder that, in the opinion of the Investigator, would interfere with participation in the study. 12. Patient has a history of neuroleptic malignant syndrome. 13. The patient has any condition that may interfere with the absorption of study medication. 14. Patient with the presence of cognitive impairment, as evidenced by a Mini-Mental State Exam (MMSE) of less than 19. 15. Patient is considered by the Investigator to be at risk of suicide or injury to self, others, or property or participants who within the past year prior to Screening have attempted suicide or have positive answers on item 4 or 5 on the Columbia Suicide Severity Rating Scale (C SSRS) at Screening(for the last 6 month period) or Day 1. 16. Patient has any existing or previous history of cancer that has been in remission for less than 5 years prior to Screening. Note: This criterion does not include those participants with basal cell, stage I squamous cell skin cancer or in situ cervical cancer. 17. Patient has a medical relevant abnormal electrocardiogram (ECG) that, in the opinion of the Investigator, increases the risks associated with participating in the study. In addition, any patient with any of the following findings will be excluded: 17.1. QT interval corrected for heart rate using Fridericia’s formula (QTcF) interval > 450 msec. 17.2. Bundle branch blocks and other conduction abnormalities that are clinically significant according to the Investigator and/or with a PR interval =220 msec, irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular or rare ventricular ectopic beats in the judgment of the Investigator, or T-wave configurations are not of sufficient quality for assessing QT interval duration. 17.3. Patient has a history of unexplained syncope or known family history of sudden death due to long QT syndrome. 18. The patients has acute or chronic hepatitis B or C infection (positive test for hepatitis B surface antigen; positive hepatitis C antibody), kn
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of 20 mg and 40 mg CPL500036 compared to placebo, on the reduction of dyskinesia based on Unified Dyskinesia Rating Scale (UDysRS) score at Week 4.;Secondary Objective: Efficacy: - To determine the effect of CPL500036 at 2 different doses, compared to placebo for anti-dyskinetic activity as measured by the following: UDysRS Objective sub-score. MDS-UPDRS total score. MDS-UPDRS Part 4/A scores. Hauser diary data: ON time including dyskinesia, troublesome dyskinesia and non-troublesome dyskinesia. Safety: - To further characterize the safety and tolerability of 20 mg and 40 mg of CPL500036 administered orally once daily for 28 days. - Number of patients with abnormal safety and tolerability assessment parameters. Pharmacokinetics: - To characterize the pharmacokinetic (PK) profile of 20 mg and 40 mg CPL500036 in Parkinson’s disease patients with Levodopa Induced Dyskinesia (LID). Exploratory: - to investigate association of Val158Met variant of COMT polymorphism with CPL500036 antidyskinetic efficacy - to investigate levels of inflammatory cytokines as CPL500036 efficacy predictive biomarkers;Primary end point(s): Change from baseline (Day 1) in total UDysRS score at Week 4 (Day 28).;Timepoint(s) of evaluation of this end point: By the end of treatment phase on Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Change from baseline in UDysRS objective sub-scale scores Part 3 and 4. The change from baseline will be derived as the average of the last 3 days of treatment objective sub-scale scores minus the average of the pre-treatment 3-day period objective sub-scale scores. Change from baseline in MDS-UPDRS total score. Change from baseline in MDS-UPDRS Part 4/A scores. Change from baseline Hauser diary data in ON time without dyskinesia or with non troublesome dyskinesia. Change from baseline Hauser diary data in ON time with dyskinesia and with troublesome dyskinesia. Safety: Physical, neurological, ophthalmological and dermatological examinations results Adverse event assessments Clinical laboratory test results (hematologic, clinical chemistry, coagulation and urinalysis) Electrocardiogram (ECG) results Pharmacokinetics: The data permitting, the following plasma PK parameters will be evaluated after single and multiple dose administration for the extensive and sparse PK sampling groups: Maximum observed concentration (Cmax) Time corresponding to the occurrence of Cmax (tmax) AUC from time zero to 24 hours (AUC0-24) AUC from time zero extrapolated to infinity (AUC0-8) Apparent terminal elimination half-life (t½) Apparent clearance (CL/F) Apparent volume of distribution during the terminal phase (Vz/F) Concentration immediately before dosing (Ctrough). This parameter will only be calculated during the multiple dose administration. Exploratory: Association of Val158Met variant of COMT polymorphism with CPL500036 antidyskinetic efficacy in subjects with LID in the course of Parkinson’s disease. Levels of inflammatory cytokines after CPL500036 administration are to be studied and compared with levels before the start of CPL500036 administration.;Timepoint(s) of evaluation of this end point: During double-blind treatment phase and follow-up period. | — |
Countries
Poland, Ukraine
Contacts
Public ContactClinical Lead Study Coordinator
Joanna Sierzputowska-Prarat
Outcome results
None listed