The aim of the study is to determine potential anti-dyskinetic properties of CPL500036 (PDE10A inhibitor) in Parkinson disease patients suffering from levodopa Induced dyskinesia. The study is to determine the efficacy and dose response of two CPL500036 doses, compared with placebo.
This is a double-blind, randomized, placebo-controlled, parallel-group, dose ranging study, to explore the efficacy, safety, tolerability and pharmacokinetic (PK) of low and high dose of CPL500036 an phosphodiesterase 10A (PDE10A) inhibitor in Parkinson's disease patients with levodopa induced dyskinesia (LID) when administered for 28 days. The study will be conducted at multiple Clinical Sites. Approximately 108 patients will be randomized at 1:1:1 ratio to receive low or high dose of CPL500036 or placebo in a blinded manner, once daily for 28 days (Day 1 to Day 28). The study will comprise of Screening, Baseline (a 4-day in-house period), a Treatment Period and a Follow-Up Period. The patients will be discharged from clinical units during the Treatment Period. Approximately 30% of the patients (11 patients in each of the 3 treatment groups) will undergo extensive PK blood sampling during the Treatment Period and the remaining 70% of the patients will undergo sparse PK blood sampling. Patients from extensive PK blood sampling will be discharged from the Clinical Site on Day 8 and Day 1 for patients from sparse PK blood sampling group respectively.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
105
CPL500036 will be given orally. Each patient is to take 2 capsules with active substance and 2 capsules of placebo daily.
CPL500036 will be given orally. Each patient is to take 4 capsules with active substance daily.
Placebo will be given orally. Each patient is to take 4 capsules of placebo daily.
Mazowiecki Szpital Bródnowski
Warsaw, Masovian Voivodeship, Poland
Change from baseline in total UDysRS score at Week 4.
Determination of the effect of low and high dose of CPL500036 compared to placebo, on the reduction of dyskinesia based on Unified Dyskinesia Rating Scale (UDysRS). The UDysRR scale is used to measure dyskinesia in Parkinson disease. Within a single scale, rater is to evaluate patient perceptions, time factors, anatomical distribution, objective impairment, severity, and disability which are accordingly divided into Part 1, Part 2, Part 3 and Part 4 of the UDysRS scale, respectively.
Time frame: Day -1, Day 28
Change from baseline in UDysRS objective sub-scale scores Part 3 and 4.
Determination of the effect of low and high dose of CPL500036 compared to placebo, on the reduction of dyskinesia based on Unified Dyskinesia Rating Scale (UDysRS). The UDysRR scale is used to measure dyskinesia in Parkinson disease. Within a single scale, rater is to evaluate patient perceptions, time factors, anatomical distribution, objective impairment, severity, and disability which are accordingly divided into Part 1, Part 2, Part 3 and Part 4 of the UDysRS scale, respectively.
Time frame: Day -1, Week 1, 2, 3 and 4
Change from baseline in MDS-UPDRS total score at Week 4
Determination of the effect of low and high dose of CPL500036 compared to placebo using Movement Disorders Society (MDS) Modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS). MDS-UPDRS is use to measure the severity and progression of Parkinson disease (PD). The MDS-UPDRS scale contain 4 parts that captures essential features of Parkinson's disease. Within a single scale, rater is to evaluate non-motor (Part 1) and motor (Part 2) experience of daily living, motor examination (Part III) and motor complications (Part IV).
Time frame: Day -1, Day 28
Change from baseline in MDS-UPDRS Part 4/A scores at Week 4
Determination of the effect of low and high dose of CPL500036 compared to placebo using Movement Disorders Society (MDS) Modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS). MDS-UPDRS is use to measure the severity and progression of Parkinson disease (PD). The MDS-UPDRS scale contain 4 parts that captures essential features of Parkinson's disease. Within a single scale, rater is to evaluate non-motor (Part 1) and motor (Part 2) experience of daily living, motor examination (Part III) and motor complications (Part IV).
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Instytut Zdrowia dr Boczarska-Jedynak Sp. Z o.o., Sp. K.,
Oświęcim, Małopolska, Poland
Cherkasy Regional Hospital of the Cherkasy Regional Council
Cherkasy, Ukraine
Ukrainian State Research Institute of Medical and Social Problems of Disability of the Ministry of Health of Ukraine, Department of Neurology and Borderline Conditions;
Dnipro, Ukraine
Treatment and Diagnostic Centre "Neuro Global" of the Limited Liability Company "Neuro Global", Treatment and Prevention Sub-division
Ivano-Frankivsk, Ukraine
Institute of Neurology, Psychiatry and Narcology of the Academy of Medical Sciences of Ukraine, Department of Vascular Pathology of the Brain and Rehabilitation
Kharkiv, Ukraine
"Medical center "Dobrobut-Polyclinic" "Medical diagnostic center "Dobrobut"
Kyiv, Ukraine
Medical Center of the Limited Liability Company "Medical Center "Consilium Medical"
Kyiv, Ukraine
"D.F. Chebotaryov Institute of Gerontology of the National Academy of Medical Sciences of Ukraine
Kyiv, Ukraine
Municipal non-profit enterprise of Lviv regional council "Lviv regional clinical hospital", Neurological Department
Lviv, Ukraine
...and 6 more locations
Time frame: Day -1, Day 28
Change from baseline in Hauser Subject Diary data in ON time with and without dyskinesia or with non-troublesome dyskinesia.
The Hauser Diary is use to monitor motor fluctuation. Patients are asked to characterize their prevailing motor states in 30-minute intervals.
Time frame: up to 6 weeks
Adverse events assessment
Number of all of adverse events will be assessed.
Time frame: up to 6 weeks
Cmax - maximum CPL500036 plasma concentration
The maximum concentration of the CPL500036 compound in plasma after IMP administration, obtained directly from the measured concentrations.
Time frame: up to 24 hours post administration on Day 1 and Day 7
Tmax - time to reach maximum CPL500036 concentration
The Tmax is time to reach the maximum plasma concentration (Cmax), obtained directly from the actual sampling times.
Time frame: up to 24 hours post administration on Day 1 and Day 7
AUC(0-24) - area under the plasma concentration - time curve from time 0 to 24 hours after IMP administration for CPL500036
The AUC(0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after IMP administration.
Time frame: up to 24 hours post administration on Day 1 and Day 7
AUC(0-inf) - area under the plasma concentration - time curve from time 0 to infinity time for CPL500036
The AUC(0-inf) is a measure of total plasma exposure to the drug from time point zero extrapolated to infinity.
Time frame: up to 24 hours post administration on Day 1 and Day 7
Kel - terminal elimination rate constant
Kel is to be estimated via linear regression of time versus log of concentration.
Time frame: up to 24 hours post administration on Day 1 and Day 7
Apparent terminal elimination half-life (T1/2) for CPL500036 compound
T1/2 is to be calculated as 0.693/Kel.
Time frame: up to 24 hours post administration on Day 1 and Day 7
Apparent clearance (CL/F) for CPL500036 compound
Apparent clearance is to be calculated as Dose/AUC(inf)
Time frame: up to 24 hours post administration on Day 1 and Day 7
Apparent volume of distribution during the terminal phase (Vz/F) for CPL500036 compound
Apparent volume of distribution is to be calculated as (CL/F)/ Kel
Time frame: up to 24 hours post administration on Day 1 and Day 7
C(trough) - CPL500036 concentration before dosing
The concentration of CPL500036 on day before product administration.
Time frame: Day 1 and Day 7
Change from baseline in inflammatory cytokines level at Week 4
Determination of the effect of low and high dose of CPL500036 compared to placebo, on the change in concentration of inflammatory cytokines in blood.
Time frame: Day 1, Day 28
Number of abnormal clinically significant findings (physical, neurological, ophthalmological and dermatological examinations).
Time frame: Up to 6 weeks
Number of abnormal clinically significant findings in clinical laboratory assessments (hematology, coagulation, clinical chemistry, urinalysis).
Time frame: Up to 6 weeks
Number of abnormal clinically significant findings in electrocardiogram results.
The following electrocardiogram parameters will be assess: PR interval, QRS interval, RR interval, QT interval and QTc interval.
Time frame: Up to 6 weeks
Number of abnormal clinically significant findings in vital signs assessments (respiratory, body temperature, blood pressure, pulse).
Time frame: Up to 6 weeks