Clinical trial NCT05297201: Efficacy, Safety and Pharmacokinetic Study of CPL500036 in Patients with Levodopa Induced Dyskinesia
Official title: Phase II, Double Blind, Randomized, Placebo Controlled, Parallel Group, Trial to Explore the Potential Anti-dyskinetic Properties of CPL500036 (PDE10A Inhibitor) in Patients with Parkinson's Disease Suffering from Levodopa Induced Dyskinesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Dyskinesia, Medication-Induced
Keywords: Parkinson's
Levodopa induced dyskinesia
Lead sponsor: Celon Pharma SA
Sponsor class: INDUSTRY
Collaborators: name: National Center for Research and Development, Poland
First posted: 2022-03-28
Enrollment: 105
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

1. Signed and dated written informed consent.
2. Male or female patient aged between 50 and 80, diagnosed of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria.
3. The patient is on stable dose of Levodopa.
4. Other anti-PD medications are allowed if dosing is optimized and stably used.
5. The patient is has been treated with Levodopa and is suffering from temporally predictable peak-dose LID.
6. Patient declare that dyskinesia is problematic or disabling.
7. Score of dyskinesia is at least 2 on part IV, item 4.2 (of the MDS-UPDRS at Screening and on Day -1).
8. Patient with Hoehn-Yahr stages 2 to 4 (in OFF stage).
9. Female patient is not pregnant (at Screening and Day -1), not breastfeeding and at least 1 of the following conditions applies: (i) woman of non-childbearing potential; (ii) woman of childbearing potential, using 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.
10. Male patient must agree to use a barrier method of contraceptive for at least 90 days after the last dose of the study drug.
11. Patient agrees to blood sample collection for DNA analysis.

Exclusion criteria:

1. The patient has (suspected) atypical Parkinson's disease.
2. The patient has a history of neurosurgical intervention because of Parkinson's disease.
3. Patient has unstable medical status which may impact the ability of the patients to participate or potentially confound the study result.
4. Patient has a history of psychotic event induced by anti-PD treatments or impulse control disorder.
5. The patient has any moderate or severe neuromuscular, locomotor disease, that interfere with the study scoring.
6. The Patient has a history of severe head injury, stroke or any diagnosis of significant nervous system disease.
7. Patient has a history of substance abuse or alcohol abuse within 12 months prior to Screening.
8. The patient is pregnant or lactating or intending to become pregnant or intending to donate ova.
9. Patient has a history of neuroleptic malignant syndrome, or known personality disorder, or other psychiatric disorder that, in the opinion of the Investigator, would interfere with participation in the study.
10. Patient with the presence of cognitive impairment evidenced by a Mini-Mental State Exam (MMSE) of less than 19.
11. Patients is considered by the Investigator to be at imminent risk of suicide or injury to self or others.
12. Patients has any existing or previous history of cancer or has newly diagnosed diabetes.
13. Patient has abnormal ECG that, in the opinion of the Investigator, increases the risks associated with participating in the study.
14. Patient has abnormal QT interval, history of unexplained syncope or known family history of sudden death due to QT abnormality.
15. The patient has any laboratory values outside the normal range that are considered by Investigator to be clinically significant at Screening.
16. Patient participated in another interventional clinical study with an IMP

Primary outcomes:
measure: Change from baseline in total UDysRS score at Week 4.
timeFrame: Day -1, Day 28
Secondary outcomes:
measure: Change from baseline in UDysRS objective sub-scale scores Part 3 and 4.
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Change from baseline in MDS-UPDRS total score at Week 4
timeFrame: Day -1, Day 28
measure: Change from baseline in MDS-UPDRS Part 4/A scores at Week 4
timeFrame: Day -1, Day 28
measure: Change from baseline in Hauser Subject Diary data in ON time with and without dyskinesia or with non-troublesome dyskinesia.
timeFrame: up to 6 weeks
measure: Adverse events assessment
timeFrame: up to 6 weeks
measure: Cmax - maximum CPL500036 plasma concentration
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: Tmax - time to reach maximum CPL500036 concentration
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: AUC(0-24) - area under the plasma concentration - time curve from time 0 to 24 hours after IMP administration for CPL500036
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: AUC(0-inf) - area under the plasma concentration - time curve from time 0 to infinity time for CPL500036
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: Kel - terminal elimination rate constant
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: Apparent terminal elimination half-life (T1/2) for CPL500036 compound
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: Apparent clearance (CL/F) for CPL500036 compound
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: Apparent volume of distribution during the terminal phase (Vz/F) for CPL500036 compound
timeFrame: up to 24 hours post administration on Day 1 and Day 7
measure: C(trough) - CPL500036 concentration before dosing
timeFrame: Day 1 and Day 7
measure: Change from baseline in inflammatory cytokines level at Week 4
timeFrame: Day 1, Day 28
measure: Number of abnormal clinically significant findings (physical, neurological, ophthalmological and dermatological examinations).
timeFrame: Up to 6 weeks
measure: Number of abnormal clinically significant findings in clinical laboratory assessments (hematology, coagulation, clinical chemistry, urinalysis).
timeFrame: Up to 6 weeks
measure: Number of abnormal clinically significant findings in electrocardiogram results.
timeFrame: Up to 6 weeks
measure: Number of abnormal clinically significant findings in vital signs assessments (respiratory, body temperature, blood pressure, pulse).
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Warszawa
country: Poland
facility: Mazowiecki Szpital Bródnowski
state: Mazowieckie
city: Oświęcim
country: Poland
facility: Instytut Zdrowia dr Boczarska-Jedynak Sp. Z o.o., Sp. K.,
state: Małopolska
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Hospital of the Cherkasy Regional Council
city: Dnipro
country: Ukraine
facility: Ukrainian State Research Institute of Medical and Social Problems of Disability of the Ministry of Health of Ukraine, Department of Neurology and Borderline Conditions;
city: Ivano-Frankivsk
country: Ukraine
facility: Treatment and Diagnostic Centre "Neuro Global" of the Limited Liability Company "Neuro Global", Treatment and Prevention Sub-division
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of the Academy of Medical Sciences of Ukraine, Department of Vascular Pathology of the Brain and Rehabilitation
city: Kyiv
country: Ukraine
facility: "Medical center "Dobrobut-Polyclinic" "Medical diagnostic center "Dobrobut"
city: Kyiv
country: Ukraine
facility: Medical Center of the Limited Liability Company "Medical Center "Consilium Medical"
city: Kyiv
country: Ukraine
facility: "D.F. Chebotaryov Institute of Gerontology of the National Academy of Medical Sciences of Ukraine
city: Lviv
country: Ukraine
facility: Municipal non-profit enterprise of Lviv regional council "Lviv regional clinical hospital", Neurological Department
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Hospital named after M.V. Sklifosovsky of the Poltava Regional Council
city: Uzhgorod
country: Ukraine
facility: Limited Liability Company, Medical Center "DIAMED"
city: Vinnytsy
country: Ukraine
facility: Medical Center of the Limited Liability Company "Salyutem Medical Center"
city: Zaporizhzhia
country: Ukraine
facility: "INET-09" LLC (Medical Center)
city: Zaporizhzhia
country: Ukraine
facility: Educational and Scientific Medical Center "University Clinic" of Zaporizhzhia State Medical University
city: Zhytomyr
country: Ukraine
facility: Communal Enterprise "Hospital" of Zhytomyr City Council
Study officials:
References: