Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients With Levodopa Induced Dyskinesia
- Conditions
- Parkinson DiseaseDyskinesia, Medication-Induced
- Interventions
- Drug: CPL500036 - high doseDrug: CPL500036 - low doseDrug: Placebo
- Registration Number
- NCT05297201
- Lead Sponsor
- Celon Pharma SA
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 108
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CPL500036 high dose CPL500036 - high dose Patients will receive 40 mg of CPL500036 administered once daily for 28-days treatment period. CPL500036 low dose CPL500036 - low dose Patients will receive 20 mg of CPL500036 administered once daily for 28-days treatment period. Placebo Placebo Patients will receive placebo administered once daily for 28-days treatment period.
- Primary Outcome Measures
Name Time Method Change from baseline in total UDysRS score at Week 4. Day -1, Day 28 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.
- Secondary Outcome Measures
Name Time Method Change from baseline in UDysRS objective sub-scale scores Part 3 and 4. Day -1, Week 1, 2, 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.
Change from baseline in MDS-UPDRS total score at Week 4 Day -1, Day 28 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).
Tmax - time to reach maximum CPL500036 concentration up to 24 hours post administration on Day 1 and Day 7 The Tmax is time to reach the maximum plasma concentration (Cmax), obtained directly from the actual sampling times.
Number of abnormal clinically significant findings (physical, neurological, ophthalmological and dermatological examinations). Up to 6 weeks Cmax - maximum CPL500036 plasma concentration up to 24 hours post administration on Day 1 and Day 7 The maximum concentration of the CPL500036 compound in plasma after IMP administration, obtained directly from the measured concentrations.
AUC(0-inf) - area under the plasma concentration - time curve from time 0 to infinity time for CPL500036 up to 24 hours post administration on Day 1 and Day 7 The AUC(0-inf) is a measure of total plasma exposure to the drug from time point zero extrapolated to infinity.
Apparent clearance (CL/F) for CPL500036 compound up to 24 hours post administration on Day 1 and Day 7 Apparent clearance is to be calculated as Dose/AUC(inf)
Adverse events assessment up to 6 weeks Number of all of adverse events will be assessed.
Kel - terminal elimination rate constant up to 24 hours post administration on Day 1 and Day 7 Kel is to be estimated via linear regression of time versus log of concentration.
Number of abnormal clinically significant findings in clinical laboratory assessments (hematology, coagulation, clinical chemistry, urinalysis). Up to 6 weeks Number of abnormal clinically significant findings in vital signs assessments (respiratory, body temperature, blood pressure, pulse). Up to 6 weeks AUC(0-24) - area under the plasma concentration - time curve from time 0 to 24 hours after IMP administration for CPL500036 up to 24 hours post administration on Day 1 and Day 7 The AUC(0-24) is a measure of total plasma exposure to the drug from time point zero to 24 hours after IMP administration.
C(trough) - CPL500036 concentration before dosing Day 1 and Day 7 The concentration of CPL500036 on day before product administration.
Apparent terminal elimination half-life (T1/2) for CPL500036 compound up to 24 hours post administration on Day 1 and Day 7 T1/2 is to be calculated as 0.693/Kel.
Change from baseline in MDS-UPDRS Part 4/A scores at Week 4 Day -1, Day 28 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).
Change from baseline in Hauser Subject Diary data in ON time with and without dyskinesia or with non-troublesome dyskinesia. up to 6 weeks The Hauser Diary is use to monitor motor fluctuation. Patients are asked to characterize their prevailing motor states in 30-minute intervals.
Change from baseline in inflammatory cytokines level at Week 4 Day 1, Day 28 Determination of the effect of low and high dose of CPL500036 compared to placebo, on the change in concentration of inflammatory cytokines in blood.
Apparent volume of distribution during the terminal phase (Vz/F) for CPL500036 compound up to 24 hours post administration on Day 1 and Day 7 Apparent volume of distribution is to be calculated as (CL/F)/ Kel
Number of abnormal clinically significant findings in electrocardiogram results. Up to 6 weeks The following electrocardiogram parameters will be assess: PR interval, QRS interval, RR interval, QT interval and QTc interval.
Trial Locations
- Locations (12)
"INET-09" LLC (Medical Center)
🇺🇦Zaporizhzhia, Ukraine
Instytut Zdrowia dr Boczarska-Jedynak Sp. Z o.o., Sp. K.,
🇵🇱Oświęcim, Małopolska, Poland
Mazowiecki Szpital Bródnowski
🇵🇱Warszawa, Mazowieckie, Poland
Treatment and Diagnostic Centre "Neuro Global" of the Limited Liability Company "Neuro Global", Treatment and Prevention Sub-division
🇺🇦Ivano-Frankivsk, Ukraine
Samodzielny Publiczny Szpital Kliniczny nr 4
🇵🇱Lublin, Lubelskie, Poland
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
Instytut Psychiatrii i Neurologii
🇵🇱Warszawa, Mazowieckie, Poland
Municipal non-profit enterprise of Lviv regional council "Lviv regional clinical hospital", Neurological Department
🇺🇦Lviv, Ukraine
Communal Enterprise "Hospital" of Zhytomyr City Council
🇺🇦Zhytomyr, Ukraine
Educational and Scientific Medical Center "University Clinic" of Zaporizhzhia State Medical University
🇺🇦Zaporizhzhia, 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
Limited Liability Company, Medical Center "DIAMED"
🇺🇦Uzhgorod, Ukraine