Phase IIb-III Study of BL-1020 Small Molecule for Schizophrenia

A Randomized, Double-Blind, Active-Controlled,Phase 2/3 Study to Determine the Short-Term (6-Week) and Long-Term (6 Month) Cognitive and Anti-Psychotic Efficacy, Safety and Tolerability of CYP-1020 Compared to Risperidone in Patients With Schizophrenia

This is a randomized, double-blind, active-controlled, 6 month study designed to evaluate the cognitive effects of treatment with CYP-1020 compared to risperidone. The primary efficacy endpoint will occur after 6 weeks of treatment; additional (secondary) efficacy endpoints will occur after 12 and 24 weeks of treatment.

Up to 450 patients will be randomized to CYP-1020 or risperidone in a 1:1 ratio. The study will utilize a flexible dose escalation scheme designed to allow patients to titrate to their maximally tolerated dose; doses of CYP-1020 may range from a minimum of 15 mg to a maximum of 35 mg, whereas doses of risperidone will range from a minimum of 1 mg to 3 mg BID (2-6 mg daily). To ensure effective blinding across all treatment groups, all patients will be treated twice daily with study drug and/or placebo, as indicated (i.e., double-dummy design).

Inclusion Criteria:

1. Male or non-pregnant or lactating female, 18-50 years of age inclusive

2. Patients must have exhibited symptoms meeting the criteria of schizophrenia for at least one year, but not more than 20 years, prior to Screening

3. Recent onset (not more than 30 days) of worsening of psychiatric symptoms at Screening.

4. Currently experiencing an acute exacerbation of schizophrenia, as defined by the following results at Screening and Baseline:

   • ≥70 total score on the PANSS
   • ≥4 (moderate) on two of the following four PANSS items: (1) delusions, (2) hallucinatory behaviors, (3) conceptual disorganization or (4) suspiciousness/persecution, where at least one of the two items must be either delusions or hallucinatory behaviors

5. CGI-S score between 4 and 6 (moderately ill to severely ill) at the Screening and Baseline visits.

6. Has exhibited a sufficient clinical response to at least one previous course of an anti-psychotic agent prescribed at a generally recognized therapeutic dose.

7. Must have completed at least 5 years of formal education or its equivalent

Exclusion Criteria:

1. Breastfeeding or pregnant
2. Symptoms of schizophrenia for more than 20 years at the time of screening.
3. Psychotic symptoms that have failed to improve (based on Investigator's opinion or documented medical history) following sufficient treatment with therapeutic doses of two or more anti-psychotics agents over the preceding 2 years
4. Prior history of neuroleptic malignant syndrome
5. Prior history or current evidence of moderate or severe tardive dyskinesia (mild is acceptable).
6. Abnormal ECG evaluation
7. History of confirmed epilepsy or prior seizure disorder (history of a single febrile seizure is not exclusionary)
8. In the opinion of the investigator, unstable medical disease (e.g., malignancy, poorly controlled diabetes or hypertension, ischemic cardiac disease, dilated cardiomyopathy or valvular heart disease, pulmonary disease, liver disease, kidney disease)
9. Acute infectious disease (e.g., malaria, dengue fever, hepatitis A), or chronic infectious disease (e.g., history of AIDS or HIV positivity, tuberculosis)
10. Likely allergy, sensitivity or intolerance to BL-1020, perphenazine, risperidone, paliperidone, or any of the drug product excipients
11. Any suicide attempt within the preceding 2 years
12. Any Substance Dependence disorder
13. High likelihood of substance abuse
14. Diagnosis with one of the following DSM-IV-TR Axis I diagnoses: schizophreniform disorder, schizoaffective disorder, bipolar disorder, substance dependency, mood disorder with psychotic features; psychotic disorder NOS
15. Requiring chronic treatment with benzodiazepines
16. Requiring chronic treatment with mood stabilizers
17. Previously treated with clozapine within 6 months prior to screening
18. Any abnormal clinical laboratory test result that is judged by the Investigator to be clinically significant
19. History of, or serologic evidence of, acute or chronic active hepatitis B or C