Cognitive Effect on Schizophrenic Patients, Schizophrenia
Conditions
Brief summary
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).
Interventions
DRUGCYP-1020
CYP-1020 (formerly known as BL-1020) is an orally available new chemical entity.
DRUGRisperidone
Sponsors
BioLineRx, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognition | Baseline and 6 weeks | To evaluate the cognitive benefits of treatment with CYP-1020 (formerly known as BL-1020) compared to risperidone after 6 weeks of treatment in patients experiencing acute exacerbation of schizophrenia. Assessed by calculating difference between CYP-1020 and Risperidone on mean change from baseline to Week 6 endpoint on MATRICS Consensus Cognition Battery (MCCB) normative composite score. MCCB is a neuropsychological test battery that comprises 10 measures of 7 different cognitive areas including speed of processing, verbal learning, memory-verbal and non verbal reasoning and problem solving, visual learning, social cognition, attention/vigilance.The study was terminated after the interim analysis. MCBB total score ranges from -50 to 150. Change from Baseline by Visit (LOCF)Higher score means better cognitive functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long Term Cognition | 12 and 24 weeks of treatment | Evaluation of the cognitive benefits of treatment with BL-1020 compared to risperidone after 12 and 24 weeks of treatment |
| Long Term Schizophrenia Treatment | Baseline and 6, 12 and 24 weeks of treatment | Evaluation of the antipsychotic efficacy of BL-1020 compared to risperidone after 6, 12 and 24 weeks of treatment |
Countries
India, Moldova, Romania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CYP-1020 CYP-1020: CYP-1020 (formerly known as BL-1020) is an orally available new chemical entity. | 133 |
| Risperidone 2-6 mg, 6 months
Risperidone | 136 |
| Total | 269 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 7 |
| Overall Study | Lack of Efficacy | 3 | 10 |
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | missing | 1 | 2 |
| Overall Study | Non compliance/Protocol deviations | 2 | 2 |
| Overall Study | Not reported | 36 | 37 |
| Overall Study | Withdrawal by Subject | 14 | 6 |
Baseline characteristics
| Characteristic | CYP-1020 | Risperidone | Total |
|---|---|---|---|
| Age, Continuous | 33.3 years STANDARD_DEVIATION 8.76 | 32.3 years STANDARD_DEVIATION 7.97 | 32.8 years STANDARD_DEVIATION 8.37 |
| Race/Ethnicity, Customized asian | 92 number of participants | 94 number of participants | 186 number of participants |
| Race/Ethnicity, Customized caucasian | 41 number of participants | 42 number of participants | 83 number of participants |
| Region of Enrollment India | 92 participants | 94 participants | 186 participants |
| Region of Enrollment Romania | 41 participants | 42 participants | 83 participants |
| Sex: Female, Male Female | 49 Participants | 49 Participants | 98 Participants |
| Sex: Female, Male Male | 84 Participants | 87 Participants | 171 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 105 / 133 | 101 / 136 |
| serious Total, serious adverse events | 6 / 133 | 5 / 136 |
Outcome results
Primary
Cognition
To evaluate the cognitive benefits of treatment with CYP-1020 (formerly known as BL-1020) compared to risperidone after 6 weeks of treatment in patients experiencing acute exacerbation of schizophrenia. Assessed by calculating difference between CYP-1020 and Risperidone on mean change from baseline to Week 6 endpoint on MATRICS Consensus Cognition Battery (MCCB) normative composite score. MCCB is a neuropsychological test battery that comprises 10 measures of 7 different cognitive areas including speed of processing, verbal learning, memory-verbal and non verbal reasoning and problem solving, visual learning, social cognition, attention/vigilance.The study was terminated after the interim analysis. MCBB total score ranges from -50 to 150. Change from Baseline by Visit (LOCF)Higher score means better cognitive functioning.
Time frame: Baseline and 6 weeks
Population: Analysis for MCCB Score ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CYP-1020 | Cognition | MCCB Baseline Score | 8.7 Scores on a scale | Standard Deviation 13.66 |
| CYP-1020 | Cognition | MCCB Week 6 Score | 13.5 Scores on a scale | Standard Deviation 12.92 |
| Risperidone | Cognition | MCCB Baseline Score | 8.2 Scores on a scale | Standard Deviation 13.86 |
| Risperidone | Cognition | MCCB Week 6 Score | 12.5 Scores on a scale | Standard Deviation 13.68 |
Secondary
Long Term Cognition
Evaluation of the cognitive benefits of treatment with BL-1020 compared to risperidone after 12 and 24 weeks of treatment
Time frame: 12 and 24 weeks of treatment
Secondary
Long Term Schizophrenia Treatment
Evaluation of the antipsychotic efficacy of BL-1020 compared to risperidone after 6, 12 and 24 weeks of treatment
Time frame: Baseline and 6, 12 and 24 weeks of treatment