Schizophrenia
Conditions
Brief summary
This is a study to evaluate the safety, efficacy, and tolerability of cariprazine (RGH-188) relative to placebo in adult patients (18-60 years of age) with acute exacerbation of schizophrenia.
Interventions
DRUGPlacebo
Placebo was supplied in capsules.
DRUGCariprazine
Cariprazine was supplied in capsules
DRUGRisperidone
Risperidone was supplied in capsules
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, 18 to 60 years of age. * Meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia (paranoid type, disorganized type, catatonic type, or undifferentiated type) based on a Structured Clinical Interview for DSM-IV (SCID). * Total Positive and Negative Syndrome Scale (PANSS) score ≥ 80 and ≤ 120. * Diagnosis of schizophrenia for at least 1 year.
Exclusion criteria
* Abnormalities on physical examination or abnormal vital signs, electrocardiogram, or clinical laboratory values. * First episode of psychosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in the PANSS Total Score | Baseline to Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a 30-item rating scale that assesses the positive and negative symptoms of individuals with schizophrenia. Responses to the 30 items are based on a structured clinical interview with the patient and on supporting clinical information obtained from family, hospital staff, or other reliable informants. Of the 30 psychiatric parameters measured by the scale, 7 assess positive symptoms (eg, delusions, grandiosity); 7 assess negative symptoms (eg, blunted affect, emotional withdrawal); and 16 assess general psychopathology (eg, poor attention, active social avoidance). Each item is scored on a 7-point scale (1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, and 7 = extreme). The PANSS total score can range from 30 to 210. A higher score indicates worse symptoms. A negative change score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in the CGI-S Score | Baseline to Week 6 | The Clinical Global Impressions-Severity (CGI-S) scale is a 7-point scale that measures the overall severity of the illness compared with the severity of illness in other patients the Investigator has observed. The Investigator assesses the severity of the patient's illness as one of the following: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patients. The CGI-S score can range from 1 to 7. A higher score indicates more severe illness. A negative change score indicates improvement. |
Countries
India, Malaysia, Russia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo orally once a day for 6 weeks. | 151 |
| Cariprazine 1.5 mg Participants received cariprazine 1.5 mg orally once a day for 6 weeks. | 145 |
| Cariprazine 3.0 mg Participants received cariprazine 3.0 mg orally once a day for 6 weeks. | 146 |
| Cariprazine 4.5 mg Participants received cariprazine 4.5 mg orally once a day for 6 weeks. | 147 |
| Risperidone 4.0 mg Participants received risperidone 4.0 mg orally once a day for 6 weeks. | 140 |
| Total | 729 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative Reasons | 0 | 1 | 0 | 2 | 0 |
| Overall Study | Adverse Event | 22 | 14 | 8 | 12 | 13 |
| Overall Study | Arrest by Police | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Death in the Family | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Did Not Receive Treatment | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Insufficient Therapeutic Response | 33 | 18 | 17 | 15 | 10 |
| Overall Study | Jeopardizing Parole Status | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 | 0 | 0 |
| Overall Study | Notification of Past Head Injury | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 1 | 3 | 1 |
| Overall Study | Withdrawal of Consent | 14 | 18 | 22 | 16 | 15 |
Baseline characteristics
| Characteristic | Cariprazine 3.0 mg | Cariprazine 4.5 mg | Placebo | Total | Cariprazine 1.5 mg | Risperidone 4.0 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 10.4 | 35.8 years STANDARD_DEVIATION 10.8 | 36.0 years STANDARD_DEVIATION 10.8 | 36.4 years STANDARD_DEVIATION 10.5 | 36.8 years STANDARD_DEVIATION 9.6 | 36.5 years STANDARD_DEVIATION 11.1 |
| Body Mass Index (BMI) | 25.6 kg/m^2 STANDARD_DEVIATION 4.6 | 24.8 kg/m^2 STANDARD_DEVIATION 4.2 | 25.2 kg/m^2 STANDARD_DEVIATION 4.5 | 25.2 kg/m^2 STANDARD_DEVIATION 4.6 | 24.9 kg/m^2 STANDARD_DEVIATION 4.9 | 25.8 kg/m^2 STANDARD_DEVIATION 4.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants | 24 Participants | 7 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 144 Participants | 143 Participants | 145 Participants | 705 Participants | 138 Participants | 135 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.7 cm STANDARD_DEVIATION 10.3 | 170.3 cm STANDARD_DEVIATION 10.4 | 170.8 cm STANDARD_DEVIATION 11.2 | 170.2 cm STANDARD_DEVIATION 10.6 | 169.0 cm STANDARD_DEVIATION 10.5 | 170.0 cm STANDARD_DEVIATION 10.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 37 Participants | 39 Participants | 36 Participants | 183 Participants | 34 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 32 Participants | 34 Participants | 171 Participants | 32 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 71 Participants | 75 Participants | 80 Participants | 370 Participants | 77 Participants | 67 Participants |
| Sex: Female, Male Female | 39 Participants | 44 Participants | 50 Participants | 227 Participants | 52 Participants | 42 Participants |
| Sex: Female, Male Male | 107 Participants | 103 Participants | 101 Participants | 502 Participants | 93 Participants | 98 Participants |
| Waist circumference | 87.6 cm STANDARD_DEVIATION 12.6 | 85.8 cm STANDARD_DEVIATION 12.7 | 86.7 cm STANDARD_DEVIATION 12.9 | 86.7 cm STANDARD_DEVIATION 12.9 | 85.2 cm STANDARD_DEVIATION 13.1 | 88.0 cm STANDARD_DEVIATION 13 |
| Weight | 74.8 kg STANDARD_DEVIATION 16.3 | 72.4 kg STANDARD_DEVIATION 16.6 | 74.4 kg STANDARD_DEVIATION 18.6 | 73.7 kg STANDARD_DEVIATION 17.5 | 71.7 kg STANDARD_DEVIATION 17.7 | 75.1 kg STANDARD_DEVIATION 18.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 151 | 0 / 145 | 0 / 146 | 0 / 147 | 0 / 140 |
| other Total, other adverse events | 67 / 151 | 73 / 145 | 74 / 146 | 87 / 147 | 80 / 140 |
| serious Total, serious adverse events | 7 / 151 | 5 / 145 | 0 / 146 | 4 / 147 | 3 / 140 |
Outcome results
Primary
Change From Baseline to Week 6 in the PANSS Total Score
The Positive and Negative Syndrome Scale (PANSS) is a 30-item rating scale that assesses the positive and negative symptoms of individuals with schizophrenia. Responses to the 30 items are based on a structured clinical interview with the patient and on supporting clinical information obtained from family, hospital staff, or other reliable informants. Of the 30 psychiatric parameters measured by the scale, 7 assess positive symptoms (eg, delusions, grandiosity); 7 assess negative symptoms (eg, blunted affect, emotional withdrawal); and 16 assess general psychopathology (eg, poor attention, active social avoidance). Each item is scored on a 7-point scale (1 = absent, 2 = minimal, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, and 7 = extreme). The PANSS total score can range from 30 to 210. A higher score indicates worse symptoms. A negative change score indicates improvement.
Time frame: Baseline to Week 6
Population: Intent-to-treat population: All participants who took at least 1 dose of double-blind investigational product and who had at least 1 post-baseline assessment of the primary efficacy parameter, the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in the PANSS Total Score | Baseline | 97.3 Units on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline to Week 6 in the PANSS Total Score | Change at Week 6 | -9.5 Units on a scale | Standard Error 1.6 |
| Cariprazine 1.5 mg | Change From Baseline to Week 6 in the PANSS Total Score | Change at Week 6 | -17.3 Units on a scale | Standard Error 1.7 |
| Cariprazine 1.5 mg | Change From Baseline to Week 6 in the PANSS Total Score | Baseline | 97.1 Units on a scale | Standard Error 0.8 |
| Cariprazine 3.0 mg | Change From Baseline to Week 6 in the PANSS Total Score | Change at Week 6 | -18.7 Units on a scale | Standard Error 1.8 |
| Cariprazine 3.0 mg | Change From Baseline to Week 6 in the PANSS Total Score | Baseline | 97.2 Units on a scale | Standard Error 0.7 |
| Cariprazine 4.5 mg | Change From Baseline to Week 6 in the PANSS Total Score | Change at Week 6 | -20.2 Units on a scale | Standard Error 1.6 |
| Cariprazine 4.5 mg | Change From Baseline to Week 6 in the PANSS Total Score | Baseline | 96.7 Units on a scale | Standard Error 0.8 |
| Risperidone 4.0 mg | Change From Baseline to Week 6 in the PANSS Total Score | Change at Week 6 | -25.3 Units on a scale | Standard Error 1.7 |
| Risperidone 4.0 mg | Change From Baseline to Week 6 in the PANSS Total Score | Baseline | 98.1 Units on a scale | Standard Error 0.8 |
p-value: 0.000595% CI: [-11.8, -3.3]ANCOVA
p-value: <0.000195% CI: [-13.1, -4.6]ANCOVA
p-value: <0.000195% CI: [-14.6, -6.2]ANCOVA
p-value: <0.000195% CI: [-19.4, -10.8]ANCOVA
Secondary
Change From Baseline to Week 6 in the CGI-S Score
The Clinical Global Impressions-Severity (CGI-S) scale is a 7-point scale that measures the overall severity of the illness compared with the severity of illness in other patients the Investigator has observed. The Investigator assesses the severity of the patient's illness as one of the following: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patients. The CGI-S score can range from 1 to 7. A higher score indicates more severe illness. A negative change score indicates improvement.
Time frame: Baseline to Week 6
Population: Intent-to-treat population: All participants who took at least 1 dose of double-blind investigational product and who had at least 1 post-baseline assessment of the primary efficacy parameter, the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in the CGI-S Score | Baseline | 4.9 Units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline to Week 6 in the CGI-S Score | Change at Week 6 | -0.6 Units on a scale | Standard Error 0.1 |
| Cariprazine 1.5 mg | Change From Baseline to Week 6 in the CGI-S Score | Baseline | 4.7 Units on a scale | Standard Error 0.1 |
| Cariprazine 1.5 mg | Change From Baseline to Week 6 in the CGI-S Score | Change at Week 6 | -0.9 Units on a scale | Standard Error 0.1 |
| Cariprazine 3.0 mg | Change From Baseline to Week 6 in the CGI-S Score | Baseline | 4.9 Units on a scale | Standard Error 0.1 |
| Cariprazine 3.0 mg | Change From Baseline to Week 6 in the CGI-S Score | Change at Week 6 | -1.1 Units on a scale | Standard Error 0.1 |
| Cariprazine 4.5 mg | Change From Baseline to Week 6 in the CGI-S Score | Change at Week 6 | -1.2 Units on a scale | Standard Error 0.1 |
| Cariprazine 4.5 mg | Change From Baseline to Week 6 in the CGI-S Score | Baseline | 4.8 Units on a scale | Standard Error 0.1 |
| Risperidone 4.0 mg | Change From Baseline to Week 6 in the CGI-S Score | Baseline | 4.8 Units on a scale | Standard Error 0.1 |
| Risperidone 4.0 mg | Change From Baseline to Week 6 in the CGI-S Score | Change at Week 6 | -1.4 Units on a scale | Standard Error 0.1 |
p-value: 0.00495% CI: [-0.6, -0.1]ANCOVA
p-value: 0.000395% CI: [-0.7, -0.2]ANCOVA
p-value: <0.000195% CI: [-0.9, -0.4]ANCOVA
p-value: <0.000195% CI: [-1.1, -0.6]ANCOVA