Schizophrenia
Conditions
Brief summary
The study will evaluate the antipsychotic efficacy of ITI-007 in a randomized, double-blind, parallel-group, placebo- and active-controlled, multi-center study in patients diagnosed with schizophrenia having an acute exacerbation of psychosis.
Interventions
Sponsors
Intra-Cellular Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* male or female subjects of any race, ages 18-60 inclusive, with a clinical diagnosis of schizophrenia * experiencing an acute exacerbation of psychosis
Exclusion criteria
* any subject unable to provide informed consent * any female subject who is pregnant or breast-feeding * any subject judged to be medically inappropriate for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | 6 weeks | The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in Clinical Global Impressions-Severity of Illness Scale | 6 weeks | The Clinical Global Impressions (CGI) Scale is a standardized assessment tool that the clinician can use to rate the severity of illness, change over time, and efficacy of medication, taking into account the subject's clinical condition and the severity of side effects. The CGI Scale consists of 3 global subscales, only one of which was used in the present study. The first subscale, Severity of Illness (CGI-S), assesses the clinician's impression of the subject's current illness state; it is often used both before and after treatment. Scores on the Severity of Illness subscale range from 1 = not ill at all to 7 = among the most extremely ill. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lumateperone 14 mg (ITI-007 20 mg Tosylate) Lumateperone 14 mg (ITI-007 20 mg Tosylate) administered orally as formulated capsules once daily for 6 weeks
ITI-007 | 172 |
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) Lumateperone 42 mg (ITI-007 60 mg Tosylate) administered orally as formulated capsules once daily for 6 weeks
ITI-007 | 172 |
| Placebo Placebo administered orally as visually-matched capsules once daily for 6 weeks
Placebo | 178 |
| Risperidone Risperidone administered orally as visually-matched over-encapsulated tablet once daily for 6 weeks
Risperidone | 173 |
| Total | 695 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 | 1 | 10 |
| Overall Study | Death | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 13 | 10 | 10 | 8 |
| Overall Study | Lost to Follow-up | 5 | 2 | 7 | 2 |
| Overall Study | Other | 3 | 3 | 2 | 10 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 34 | 30 | 20 | 37 |
Baseline characteristics
| Characteristic | Risperidone | Total | Lumateperone 14 mg (ITI-007 20 mg Tosylate) | Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 42.4 years STANDARD_DEVIATION 10.77 | 42.6 years STANDARD_DEVIATION 10.13 | 42.7 years STANDARD_DEVIATION 9.99 | 41.9 years STANDARD_DEVIATION 9.88 | 43.5 years STANDARD_DEVIATION 9.9 |
| Positive and Negative Syndrome Scale (PANSS) Total Score | 90.0 units on a scale STANDARD_DEVIATION 9.6 | 89.9 units on a scale STANDARD_DEVIATION 9.89 | 88.7 units on a scale STANDARD_DEVIATION 9.86 | 90.9 units on a scale STANDARD_DEVIATION 10.26 | 90.0 units on a scale STANDARD_DEVIATION 9.81 |
| Race/Ethnicity, Customized Asian | 2 Participants | 7 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Back or African American | 123 Participants | 536 Participants | 140 Participants | 140 Participants | 133 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 21 Participants | 4 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 40 Participants | 131 Participants | 26 Participants | 30 Participants | 35 Participants |
| Sex: Female, Male Female | 41 Participants | 183 Participants | 47 Participants | 49 Participants | 46 Participants |
| Sex: Female, Male Male | 132 Participants | 512 Participants | 125 Participants | 123 Participants | 132 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 | 0 / 172 | 0 / 172 | 0 / 178 | 1 / 173 |
| other Total, other adverse events | 57 / 172 | 76 / 172 | 68 / 178 | 79 / 173 |
| serious Total, serious adverse events | 0 / 172 | 1 / 172 | 0 / 178 | 0 / 173 |
Outcome results
Primary
Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms.
Time frame: 6 weeks
Population: Analysis was conducted using the ITT analysis set, which includes all subjects who were randomized, received at least 1 dose of study medication, and had a valid baseline and at least 1 valid post-baseline PANSS measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 14 mg (ITI-007 20 mg Tosylate) | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | -15.0 units on a scale | Standard Error 1.27 |
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | -14.6 units on a scale | Standard Error 1.23 |
| Placebo | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | -15.1 units on a scale | Standard Error 1.21 |
| Risperidone | Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | -20.5 units on a scale | Standard Error 1.33 |
p-value: 0.97295% CI: [-3.39, 3.51]Mixed Models for Repeated Measure
p-value: 0.78995% CI: [-2.92, 3.84]Mixed Effects Model for Repeated Measure
Secondary
Change From Baseline to Week 6 in Clinical Global Impressions-Severity of Illness Scale
The Clinical Global Impressions (CGI) Scale is a standardized assessment tool that the clinician can use to rate the severity of illness, change over time, and efficacy of medication, taking into account the subject's clinical condition and the severity of side effects. The CGI Scale consists of 3 global subscales, only one of which was used in the present study. The first subscale, Severity of Illness (CGI-S), assesses the clinician's impression of the subject's current illness state; it is often used both before and after treatment. Scores on the Severity of Illness subscale range from 1 = not ill at all to 7 = among the most extremely ill.
Time frame: 6 weeks