Study of CYR-101 in Patients With Schizophrenia

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: CYR-101

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Toul, France, 54201
    • Centre Hospitalier Universitaire de Nancy (CHU)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: CYR-101; Experimental arm
Placebo Comparator: 2	Drug: Placebo; Placebo comparator

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Cyrenaic Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: March 11, 2009
• First Submitted That Met QC Criteria: March 12, 2009
• First Posted (Estimate): March 13, 2009

Study Record Updates

• Last Update Posted (Estimate): June 8, 2011
• Last Update Submitted That Met QC Criteria: June 6, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: CYR-101C01