Clinical trial NCT05278156: Efficacy, Safety and Pharmacokinetics Study of CPL500036 (PDE10A Inhibitor) in Patients With Schizophrenia
Official title: Phase II, Double Blind, Randomized, Placebo Controlled, Parallel Group, Trial to Explore Efficacy, Safety and Pharmacokinetics of CPL500036 (PDE10A Inhibitor) in Patients With an Acute Exacerbation of Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Celon Pharma SA
Sponsor class: INDUSTRY
Collaborators: name: National Center for Research and Development, Poland
First posted: 2022-03-14
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy, safety, tolerability and pharmacokinetics (PK) properties of CPL500036 compound (PDE10a inhibitor) in patients with an acute exacerbation of schizophrenia after 28 days of administration..

Detailed description: This is a double-blind, randomized, placebo controlled, parallel group, dose ranging study to explore the efficacy, safety, tolerability and PK of 2 different doses of CPL500036 (phosphodiesterase 10A \[PDE10A\] inhibitor) in patients with an acute exacerbation of schizophrenia. Approximately 165 patients will be randomized at a 1:1:1 ratio and will be dosed with 20 mg CPL500036, 40 mg CPL500036 or placebo once daily for 28 consecutive days (Day 1 to Day 28). Patients will remain in house for the duration of the Treatment Period. The study will comprise of a Screening Period (that will include a prior Medication Washout Period), a Treatment Period and a Follow-up Period. After discharge from the Clinical Unit, patients will return to the Clinical Unit for 2 once weekly Follow-up Visits. Approximately 30% of the patients (17 patients in each of the 3 treatment groups) will undergo extensive PK sampling during the Treatment Period, and the remaining 70% of the patients will only undergo sparse PK sampling.

Eligibility criteria: Inclusion Criteria:

1. The patient has a primary diagnosis of schizophrenia confirmed by clinical interview \[SCID-5-CT\].
2. Male or female patient aged 18 to 65, inclusive, at Screening.
3. The patient's with exacerbation of psychotic symptoms
4. The patient has a score of 5 or higher in 3 or more items of the following PANSS items at Screening and Baseline
5. The patient has a PANSS Total Score of 80 or higher during Screening and on Baseline
6. The patient of childbearing potential willing to use acceptable forms of contraception.
7. The patient has a score in CGI-S scale of 4 or greater at Screening and on Baseline
8. The patient is able to and agrees to remain off prior antipsychotic medication and all excluded medications as outlined in the protocol for the duration of the Treatment Period.
9. The patient is able to sign informed consent after receiving information about the trial and has the ability and willingness to comply with the requirements and restrictions of the study protocol.

Exclusion Criteria:

1. The patient has a decrease in the PANSS Total Score at Baseline compared with the Total Score at Screening.
2. Patient who recently participated in another interventional clinical study with an Investigational Medicinal Product.
3. The patient has uncontrolled abnormality which may impact the ability of the patient to participate or potentially confound the study results.
4. The patient has a history of severe head injury, traumatic brain injury, myocardial infarction or stroke.
5. The patient has a moderate or severe substance use disorder for alcohol or other substances of abuse except nicotine or caffeine.
6. The patient is pregnant or lactating or intending to become pregnant or intending to donate ova.
7. The 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.
8. The patient is considered by the Investigator to be at imminent risk of suicide or injury to self or others.
9. The patient has chronic movement disorder that may interfere with the interpretation of study results.
10. The patient has any existing or previous history of cancer or has newly diagnosed diabetes.
11. The patient has long QT syndrome or is under treatment with antiarrhythmic drugs.
12. The patient is considered to be treatment resistant. .
13. The patient has received electroconvulsive therapy.
14. The patient has any laboratory values outside the normal range that are considered by the Investigator to be clinically significant at Screening.

Primary outcomes:
measure: Change from baseline in PANSS positive subscale at Day 28.
timeFrame: Day -1, Day 28
Secondary outcomes:
measure: Change from baseline in PANSS positive subscale at Week 1, 2 and 3
timeFrame: Day -1, Week 1, 2 and 3
measure: Change from baseline in PANSS Total Score at Weeks 1, 2, 3, 4
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Change from Baseline in PANSS Subscales Using the Marder 5 factor Model at Weeks 1, 2, 3, and 4
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Change from Baseline in PANSS Negative Subscales at Weeks 1, 2, 3 and 4
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Change from Baseline in PANSS general psychopathology Subscale at Weeks 1, 2, 3 and 4
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Percentage of Clinical Responders Based on the PANSS Total Score.
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Change from Baseline in Clinical Global Impression Severity (CGI-S) Score at Weeks 1, 2, 3, and 4
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Clinical Global Impression Scale Improvement (CGI-I) Score at Weeks 1, 2, 3, 4.
timeFrame: Day -1, Week 1, 2, 3 and 4
measure: Change from Baseline in Brief Assessment of Cognition in Schizophrenia (BACS) Score at Weeks 2 and 4.
timeFrame: Day -1, Week 2 and 4
measure: Number of abnormal clinically significant values in vital signs (heart rate, blood pressure, respiratory rate) results.
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 values in laboratory tests (hematologic, clinical chemistry, coagulation and urinalysis) results.
timeFrame: up to 6 weeks
measure: Number of abnormal physical, neurological, ophthalmological and dermatological examination findings.
timeFrame: up to 6 weeks
measure: Number and intensity of extrapyramidal side effects.
timeFrame: up to 6 weeks
measure: Number of adverse events.
timeFrame: up to 6 weeks
measure: CPL500036 Cmax - Maximum observed concentration
timeFrame: up to 24 hours after administration on Day 7
measure: CPL500036 Tmax - Time corresponding to occurrence of Cmax
timeFrame: up to 24 hours after administration on Day 7
measure: CPL500036 AUC (0-24h) - Area under the curve from time zero to 24 hours
timeFrame: up to 24 hours after administration on Day 7
measure: CPL500036 AUC T1/2 - Apparent terminal elimination half-life
timeFrame: up to 24 hours after administration on Day 7
measure: CPL500036 CL/F (Apparent clearance) and Vz/F (apparent volume of distribution during terminal phase)
timeFrame: up to 24 hours after administration on Day 7
measure: CPL500036 Cthrough - Concentration immediately prior to dosing
timeFrame: up to 24 hours after administration on Day 7
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Department of Psychiatry and Psychotheraapy of Semmelweis University
city: Budapest
country: Hungary
facility: Semmelweis University, Faculty of Medicine, Department of Psychiatry and Psychotherapy
city: Győr
country: Hungary
facility: Department of Psychiatry, Mental hygiene and Addictology of Petz Aladár County Teaching Hospital
city: Kalocsa
country: Hungary
facility: Bács-Kiskun County Teaching Hospital Kalocsa Holy Cross Hospital
city: Szekszárd
country: Hungary
facility: Psychiatry Department of Tolna County Balassa Janos Hospital
city: Białystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny
city: Bolesławiec
country: Poland
facility: Wojewódzki Szpital dla Nerwowo i Psychicznie Chorych
city: Choroszcz
country: Poland
facility: Samodzielny Publiczny Psychiatryczny Zakład Opieki Zdrowotnej
city: Świecie
country: Poland
facility: Wojewódzki Szpital dla Psychicznie i Nerwowo Chorych
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk National Medical University, Department of Psychiatry, Narcology and Medical Psychology
city: Kyiv
country: Ukraine
facility: Communal non-profit enterprise "Clinical Hospital "PSYCHIATRY"" of the executive body of the Kyiv City Council (Kyiv City State Administration), Center for Primary Psychotic Episode and Modern Treatment Methods.
city: Kyiv
country: Ukraine
facility: Communal non-commercial enterprise of the Kyiv Regional Council "Regional Psychiatric-Narcological Medical Association", women's department No. 2, men's department No. 10.
city: Lviv
country: Ukraine
facility: Communal non-commercial enterprise of the Lviv Regional Council "Lviv Regional Clinical Psychoneurological Dispensary",
city: Lviv
country: Ukraine
facility: Communal non- commercial enterprise of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital",
city: Ternopil
country: Ukraine
facility: Ternopil National Medical University named after I.Y. Gorbachevskiy of the Ministry of Health of Ukraine, Department of Psychiatry, Narcology and Medical Psychology
city: Vinnytsia
country: Ukraine
facility: Vinnytsia National Medical University named after M.I. Pirogov, Department of Psychiatry, Narcology and Psychotherapy with a course of postgraduate education
Study officials:
References: