Chronic Schizophrenia
Conditions
Keywords
Schizophrenia, SM-13496, Latuda, Lurasidone
Brief summary
Lurasidone HCl is a compound being developed for the treatment of schizophrenia. This clinical study is designed to test the hypothesis that lurasidone is effective, tolerable, and safe as compared with quetiapine XR long term among schizophrenic outpatients with chronic schizophrenia.
Interventions
DRUGLurasidone HC1
Lurasidone 40-160 mg/day flexibly dosed.
DRUGQuetiapine XR
Quetiapine XR 200-800 mg/day flexibly dosed.
Sponsors
Sumitomo Pharma America, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Entry Criteria: * Screening for the present study will take place after subjects' participation in Study D1050233 has been completed, and after providing informed consent. Inclusion Criteria: * Completed all required assessments on the final study visit in Study D1050233. * Suitable for treatment in an outpatient setting.
Exclusion criteria
* Any chronic organic disease of the CNS (other than schizophrenia). * Considered by the investigator to be at imminent risk of suicide or injury to self, others, or property.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse of Psychotic Symptoms | 12 Months | Time to relapse will be defined as the earliest occurrence of any of the following: * Worsening of \>= 30% positive and negative syndrome scale total score from NCT00790192 and clinical global impression-severity sub-scale \>=3 * rehospitalization for worsening of psychosis * emergence of suicidal ideation, homicidal ideation and/or risk of harm to self or others Comparison of time to relapse of psychotic symptoms between lurasidone and quetiapine XR after 1 year as analyzed using the Cox proportional hazard model with country as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From the Acute Phase Baseline to Month 6 of the Double-blind Treatment in the CogState Computerized Cognitive Scores. | Baseline and 6 Months | The battery has seven outcome measures that measure the cognitive constructs. The seven domains are: detection, identification, one back task, international shopping list task, one card learning task, Groton maze learning task and social emotional matching. The standardized scores for each subject at each assessment will then be averaged to yield a composite score. There are no maximum or minimum values, however a higher score indicates improved performance on the cognitive constructs. The change score is change from baseline to month 6. |
| Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Positive and Negative Syndrome Scale (PANSS) | Baseline and 12 months | The PANSS is an interview-based measure of psychopathology severity in adults with psychotic disorders. Thirty items are rated using a Likert scale, from 1 - 7. The PANSS total score is the sum of thirty items ranging from 30 to 210 (higher score representing a worsening in psychosis). |
| Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Clinical Global Impression Severity Scale (CGI-S) Scores | Baseline and 12 months | The CGI-S is a clinician-rated assessment of the subject's current illness state on a scale ranging from 1-7, where a higher score is associated with greater illness severity. |
Countries
Colombia, India, Romania, Russia, Ukraine, United States
Participant flow
Pre-assignment details
Patients transitioned from the acute phase study (D1050233 -NCT00790192) to the current study (D1050234) in a non-randomized fashion.
Participants by arm
| Arm | Count |
|---|---|
| Lurasidone 80mg Lurasidone 80mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study. | 72 |
| Lurasidone 160 mg Lurasidone 160mg/day in the acute phase study and flexibly-dosed lurasidone (40mg/day to 160mg/day) in the current study. | 79 |
| Placebo-Lurasidone Placebo in the acute phase study and flexibly-dosed lurasidone (40 mg/day to 160 mg/day) in the current study | 56 |
| Quetiapine-Quetiapine Quetiapine XR 600 mg/day in the acute phase study and flexibly-dosed quetiapine XR (200 mg/day to 800 mg/day) in the current study | 85 |
| Total | 292 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative | 0 | 3 | 3 | 1 |
| Overall Study | Adverse Event | 5 | 5 | 3 | 4 |
| Overall Study | Lack of Efficacy | 10 | 4 | 5 | 18 |
| Overall Study | Lost to Follow-up | 5 | 5 | 2 | 9 |
| Overall Study | Protocol Violation | 6 | 1 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 15 | 12 | 19 |
Baseline characteristics
| Characteristic | Lurasidone 160 mg | Total | Quetiapine-Quetiapine | Lurasidone 80mg | Placebo-Lurasidone |
|---|---|---|---|---|---|
| Age, Continuous | 37.6 years STANDARD_DEVIATION 11.7 | 37.6 years STANDARD_DEVIATION 11.3 | 38.5 years STANDARD_DEVIATION 10.4 | 36.6 years STANDARD_DEVIATION 11.7 | 37.5 years STANDARD_DEVIATION 11.4 |
| Region of Enrollment Colombia | 3 participants | 15 participants | 4 participants | 5 participants | 3 participants |
| Region of Enrollment India | 22 participants | 66 participants | 13 participants | 15 participants | 16 participants |
| Region of Enrollment Romania | 9 participants | 27 participants | 10 participants | 6 participants | 2 participants |
| Region of Enrollment Russian Federation | 15 participants | 55 participants | 17 participants | 11 participants | 12 participants |
| Region of Enrollment Ukraine | 15 participants | 59 participants | 18 participants | 17 participants | 9 participants |
| Region of Enrollment United States | 15 participants | 70 participants | 23 participants | 18 participants | 14 participants |
| Sex: Female, Male Female | 27 Participants | 97 Participants | 33 Participants | 16 Participants | 21 Participants |
| Sex: Female, Male Male | 52 Participants | 195 Participants | 52 Participants | 56 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 72 | 51 / 79 | 35 / 56 | 53 / 85 |
| serious Total, serious adverse events | 9 / 72 | 6 / 79 | 2 / 56 | 17 / 85 |
Outcome results
Primary
Relapse of Psychotic Symptoms
Time to relapse will be defined as the earliest occurrence of any of the following: * Worsening of \>= 30% positive and negative syndrome scale total score from NCT00790192 and clinical global impression-severity sub-scale \>=3 * rehospitalization for worsening of psychosis * emergence of suicidal ideation, homicidal ideation and/or risk of harm to self or others Comparison of time to relapse of psychotic symptoms between lurasidone and quetiapine XR after 1 year as analyzed using the Cox proportional hazard model with country as a covariate.
Time frame: 12 Months
Population: The population for relapse analyses is the relapse population which consists of those subjects who are enrolled in the present study, demonstrated response to 6 weeks of treatment with either lurasidone or quetiapine XR in study D1050233-NCT 00790192, and who took at least one dose of study medication in the present study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lurasidone-Lurasidone | Relapse of Psychotic Symptoms | 29 participants |
| Quetiapine-Quetiapine | Relapse of Psychotic Symptoms | 21 participants |
Comparison: Comparison of time to relapse of psychotic symptoms between LUR-LUR and QXR-QXR as analyzed using the Cox proportional-hazards model.95% CI: [0.41, 1.295]COX Proportional Hazards Model
Secondary
Change From the Acute Phase Baseline to Month 6 of the Double-blind Treatment in the CogState Computerized Cognitive Scores.
The battery has seven outcome measures that measure the cognitive constructs. The seven domains are: detection, identification, one back task, international shopping list task, one card learning task, Groton maze learning task and social emotional matching. The standardized scores for each subject at each assessment will then be averaged to yield a composite score. There are no maximum or minimum values, however a higher score indicates improved performance on the cognitive constructs. The change score is change from baseline to month 6.
Time frame: Baseline and 6 Months
Population: The population is the intent to treat population which consists of those enrolled subjects who receive at least one dose of study medication and have either a PANSS or CGI-S baseline and post baseline measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lurasidone-Lurasidone | Change From the Acute Phase Baseline to Month 6 of the Double-blind Treatment in the CogState Computerized Cognitive Scores. | 0.22 units on a scale |
| Quetiapine-Quetiapine | Change From the Acute Phase Baseline to Month 6 of the Double-blind Treatment in the CogState Computerized Cognitive Scores. | -0.03 units on a scale |
Secondary
Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Clinical Global Impression Severity Scale (CGI-S) Scores
The CGI-S is a clinician-rated assessment of the subject's current illness state on a scale ranging from 1-7, where a higher score is associated with greater illness severity.
Time frame: Baseline and 12 months
Population: The population is the intent to treat population which consists of those enrolled subjects who receive at least one dose of study medication and have either a PANSS or CGI-S baseline and post baseline measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lurasidone-Lurasidone | Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Clinical Global Impression Severity Scale (CGI-S) Scores | -1.9 units on a scale |
| Quetiapine-Quetiapine | Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Clinical Global Impression Severity Scale (CGI-S) Scores | -1.6 units on a scale |
Secondary
Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Positive and Negative Syndrome Scale (PANSS)
The PANSS is an interview-based measure of psychopathology severity in adults with psychotic disorders. Thirty items are rated using a Likert scale, from 1 - 7. The PANSS total score is the sum of thirty items ranging from 30 to 210 (higher score representing a worsening in psychosis).
Time frame: Baseline and 12 months
Population: The population is the intent to treat population which consists of those enrolled subjects who receive at least one dose of study medication and have either a PANSS or CGI-S baseline and post baseline measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lurasidone-Lurasidone | Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Positive and Negative Syndrome Scale (PANSS) | -34.6 units on a scale |
| Quetiapine-Quetiapine | Change From the Acute Phase Baseline to the End (Month 12) of the Double-blind Treatment in the Positive and Negative Syndrome Scale (PANSS) | -25.7 units on a scale |