Study of CYR-101 in Patients With Schizophrenia

Study Overview
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Brief Summary
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This Phase II study will test whether CYR-101, a CNS-active compound with novel pharmacological profile and devoid of dopamine D2 receptor binding properties, is efficacious when administered orally in the management of patients with a diagnosis of DSM-IV schizophrenia.

Official Title
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A Multi-center, Inpatient and Ambulatory, Phase 2, Double Blind, Randomized, Placebo-controlled Proof of Concept Study of CYR-101 in Patients With DSM-IV Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: CYR-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, 18 to 65 years of age, inclusive Female patients must test negative for pregnancy and, if of childbearing potential, must be using a medically accepted means of contraception. Patients must have a diagnosis of Schizophrenia or schizo-affective disorders as defined in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revised (DSM-IV TR, APA 2000) (Disorganised, 295.10; Catatonic, 295.20; Paranoid, 295.30; Residual, 295.60; or Undifferentiated, 295.90) and confirmed by the Structured Clinical Interview for DSM-IV (SCID). Patients must meet the following psychopathologic severity criteria at screening: Positive and Negative Syndrome Scale (PANSS) total score, of at least 60. Patients must receive a rating of 4 (moderately ill) or greater on the Clinical Global Impression-Severity (CGI-S) scale at screening. Patients in whom, in the opinion of the investigator, a switch to another antipsychotic medication or initiation of an antipsychotic medication is indicated. Patients must be considered reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol. Patients must be able to understand the nature of the study and have given their own informed consent. Exclusion Criteria: Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. Have received treatment with a drug that has not received regulatory approval for any indication within 30 days prior to screening. Patients in whom treatment with CYR-101, or placebo, as specified in this protocol, is relatively or absolutely clinically contraindicated. Patients who have a history of an inadequate response, in the opinion of the investigator, to 2 or more adequate antipsychotic medication trials of at least 8 weeks duration in the past 12 months prior to screening. Patients who require concomitant treatment with any other medication with primary central nervous system activity, other than certain allowed medications as specified in Study Protocol. Patients receiving treatment with depot antipsychotic medication within 1 dosing interval, minimum of 4 weeks, prior to screening. Actively suicidal (for example any suicide attempts within the past month or any current suicidal intent including plan) in the opinion of the investigator or a score of 4 or greater on Item 10 of the Montgomery-Asberg Depression Rating Scale (MADRS). DSM-IV diagnosis of substance dependence or substance abuse (except nicotine and caffeine) within the 6 months prior to screening. Diagnosis of substance-induced psychosis by DSM-IV criteria within 7 days of screening (or at any time during the study). Patients with current heteroaggressive behavior. Female patients who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study. Have increased risk of seizures as evidenced by a history of: one or more seizures (except childhood febrile seizure), history of electroencephalogram (EEG) with epileptiform activity, history of stroke; surgery to the cerebral cortex; or head trauma with loss of consciousness. NOTE: patients with a history of childhood febrile seizure may be enrolled in this study. Patients who have had electroconvulsive therapy (ECT) within 3 months of screening visit or who will have ECT at any time during the study. Test HIV positive. Test positive for Hepatitis C antibody or Hepatitis B surface antigen (HBsAg). Patients with positive Hepatitis B core antibody test and negative HBsAg may be included in the study if aminotransferase levels (ALT/SGPT and AST/SGOT) do not exceed 1.5 times upper limit of normal (ULN). Alanine transaminase/serum glutamic-pyruvic transaminase (ALT/SGPT) values >1.5 times ULN of the performing laboratory, or total bilirubin values >2 times the ULN or concomitant ALT/SGPT values >1.5 times the ULN and total bilirubin values >1.5 times the ULN at screening. Patients with acute, serious, or unstable medical conditions, including (but not limited to) inadequately controlled diabetes (hemoglobin A1c (HbA1c) >8%), severe hypertriglyceridemia (fasting triglycerides >5.6 mmol/L, recent cerebrovascular accidents, serious acute systemic infection or immunologic disease, unstable cardiovascular disorders (including ischemic heart disease), malnutrition, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, or haematologic diseases. Prolactin level at screening visit of greater than 200 ng/mL (or 200mg/L). A diagnosis of Parkinson's disease, dementia-related psychosis, or related disorders. If a patient has a past misdiagnosis of Parkinson's disease, dementia-related psychosis, or related disorders, the investigator will need to contact the Clinical Research Physician prior to enrolment. Patient with current clinically significant cardiovascular disease. History of syncopal events due to cardiovascular abnormality.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: CYR-101<br>* Experimental arm<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global PANSS score and sub-scores |  | one month (28 days +/- 2 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PANSS total score and sub-scores |  | Three months (84 days +/- 2 days) | 
| CGI-S, DAI-10, PSQI, BACS, MADRS, HAMA. |  | three months (84 days +/- 2 days) |