Schizophrenia
Conditions
Keywords
Schizophrenia, Acute Schizophrenia, Psychotropic Drugs, Antipsychotic Agents, Mental Disorders, Dopamine Agents, Central Nervous System Agents
Brief summary
The objective of this study is to evaluate the efficacy, safety, and tolerability of cariprazine relative to placebo for the treatment of acute exacerbation of schizophrenia.
Interventions
DRUGCariprazine
Patients who meet eligibility criteria will be administered a once daily oral dose of cariprazine for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.
DRUGPlacebo
Patients who meet eligibility criteria will be administered a once daily oral dose of placebo for six weeks. Upon completion of the study or early termination, patients will undergo a two week safety follow-up period.
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have provided informed consent prior to any study specific procedures * Patients currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for schizophrenia (paranoid type, disorganized type, catatonic type or undifferentiated type), as confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) * Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCIPANSS) total score ≥ 80 and ≤ 120 * Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 * Patients with normal physical examination, laboratory, vital signs,and/ or electrocardiogram (ECG)
Exclusion criteria
* Patients with a DSM-IV-TR diagnosis of Schizoaffective disorder, schizophreniform disorder, other psychotic disorders other than schizophrenia, or bipolar I or II disorder * Patients in their first episode of psychosis * Pregnant, breast-feeding, and/or planning to become pregnant and/or breastfeed during the study * Pervasive developmental disorder, mental retardation, delirium, dementia, amnestic and other cognitive disorders * Known or suspected borderline or antisocial personality disorder or other DSM-IV-TR axis II disorder of sufficient severity to interfere with participation in this study * Substance abuse or dependence within the prior 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline to Week 6 | The Positive and Negative Syndrome Scale is a 30-item rating scale specifically developed to asses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS total score is rated based on a structured clinical interview with the patient and supporting clinical information obtained from family, hospital staff, or other reliable informants. This assessment provides scores in 9 clinical domains, including a positive syndrome, a negative syndrome, depression, a composite index, and general psychopathology. Each item is scored on a 7-point (1 to 7) scale, with 1 being minimal impact, and 7 being highest impact. The cumulative score ranges from 30 to 210. A negative change score indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Schizophrenia Symptoms: Change From Baseline in Clinical Global Impression-Severity (CGI-S) | Baseline to Week 6 | The Clinical Global Impressions-Severity scale is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of illness in other participants the physician has observed. The participant is rated on a scale from 1 to 7 with 1 indicating a normal state and 7 indicating among the most extremely ill participants. A higher score indicates greater illness. A negative change score indicates improvement. |
Countries
Colombia, India, South Africa, United States
Participant flow
Pre-assignment details
Randomization and treatment assignment were based on a randomization scheme prepared by Allergan Biostatistics prior to the start of the study. No-drug washout period of up to 7 days.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Oral administration. Once per day. | 147 |
| Cariprazine (3-6 mg/Day) Oral administration. Once per day. | 151 |
| Cariprazine (6-9 mg/Day) Oral administration. Once per day. | 148 |
| Total | 446 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 13 | 14 | 13 |
| Overall Study | Did not meet inc/exc criteria | 1 | 1 | 1 |
| Overall Study | Lack of Efficacy | 26 | 12 | 13 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Other reasons | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 16 | 25 | 32 |
Baseline characteristics
| Characteristic | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-9 mg/Day) | Total |
|---|---|---|---|---|
| Age, Continuous | 36.7 Years STANDARD_DEVIATION 11.3 | 36.6 Years STANDARD_DEVIATION 10.5 | 35.5 Years STANDARD_DEVIATION 9.3 | 36.3 Years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 24 Participants | 27 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 124 Participants | 127 Participants | 121 Participants | 372 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 56 Participants | 56 Participants | 56 Participants | 168 Participants |
| Race/Ethnicity, Customized Black or African-American | 51 Participants | 56 Participants | 53 Participants | 160 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 12 Participants | 10 Participants | 6 Participants | 28 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 28 Participants | 30 Participants | 84 Participants |
| Sex/Gender, Customized Female | 37 Participants | 33 Participants | 35 Participants | 105 Participants |
| Sex/Gender, Customized Male | 110 Participants | 118 Participants | 113 Participants | 341 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 147 | 0 / 151 | 0 / 148 |
| other Total, other adverse events | 54 / 147 | 84 / 151 | 86 / 148 |
| serious Total, serious adverse events | 13 / 161 | 9 / 167 | 4 / 169 |
Outcome results
Primary
Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score
The Positive and Negative Syndrome Scale is a 30-item rating scale specifically developed to asses both the positive and negative symptom syndromes of patients with schizophrenia. The PANSS total score is rated based on a structured clinical interview with the patient and supporting clinical information obtained from family, hospital staff, or other reliable informants. This assessment provides scores in 9 clinical domains, including a positive syndrome, a negative syndrome, depression, a composite index, and general psychopathology. Each item is scored on a 7-point (1 to 7) scale, with 1 being minimal impact, and 7 being highest impact. The cumulative score ranges from 30 to 210. A negative change score indicates improvement.
Time frame: Baseline to Week 6
Population: Intent-to-Treat Population, consisting of all patients in the Safety Population who had at least one postbaseline assessment of the PANSS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score | -16.0 Units on a Scale | Standard Error 1.6 |
| Cariprazine (3-6 mg/Day) | Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score | -22.8 Units on a Scale | Standard Error 1.6 |
| Cariprazine (6-9 mg/Day) | Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score | -25.9 Units on a Scale | Standard Error 1.7 |
p-value: 0.002995% CI: [-11.3, -2.4]ANCOVA
p-value: <0.000195% CI: [-14.5, -5.3]ANCOVA
Secondary
Measurement of Schizophrenia Symptoms: Change From Baseline in Clinical Global Impression-Severity (CGI-S)
The Clinical Global Impressions-Severity scale is a clinician-rated scale that measures the overall severity of a participant's illness in comparison with the severity of illness in other participants the physician has observed. The participant is rated on a scale from 1 to 7 with 1 indicating a normal state and 7 indicating among the most extremely ill participants. A higher score indicates greater illness. A negative change score indicates improvement.
Time frame: Baseline to Week 6
Population: Intent-to-Treat Population, consisting of all patients in the Safety Population who had at least one postbaseline assessment of the PANSS total score.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Measurement of Schizophrenia Symptoms: Change From Baseline in Clinical Global Impression-Severity (CGI-S) | -1.0 units on a scale | Standard Error 0.1 |
| Cariprazine (3-6 mg/Day) | Measurement of Schizophrenia Symptoms: Change From Baseline in Clinical Global Impression-Severity (CGI-S) | -1.4 units on a scale | Standard Error 0.1 |
| Cariprazine (6-9 mg/Day) | Measurement of Schizophrenia Symptoms: Change From Baseline in Clinical Global Impression-Severity (CGI-S) | -1.6 units on a scale | Standard Error 0.1 |
p-value: 0.011595% CI: [-0.6, -0.1]ANCOVA
p-value: <0.000195% CI: [-0.8, -0.3]ANCOVA