Schizophrenia
Conditions
Keywords
Schizophrenia, Schizophrenic disorder
Brief summary
The objective of this study is to evaluate the efficacy and safety of cariprazine relative to placebo in the prevention of relapse of symptoms in participants with schizophrenia.
Detailed description
There were 3 periods (phases) in the study. The Open-label Phase lasted 20 weeks. In the first 6 weeks, participants received 3, 6, or 9 mg cariprazine orally once a day; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this Open-label Phase. At the end of Week 8, participants had to meet the following criteria to continue in the study. * Positive and Negative Syndrome Scale (PANSS) total score ≤ 60 at the end of Week 8 * At least 20% decrease in PANSS total score from baseline to the end of Week 8 * Clinical Global Impressions - Severity (CGI-S) score ≤ 4 at the end of Week 8 * Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 8 * Stable dose during the previous 2 weeks * No significant tolerability issues as judged by the Investigator at the end of Week 8 At the end of the Open-label Phase, participants were randomized into 2 treatment groups, cariprazine or placebo, if they met the following criteria: * PANSS total score ≤ 60 at the end of Week 20 * At least 20% decrease in PANSS total score from baseline to the end of Week 20 * CGI-S score ≤ 4 at the end of Week 20 * Score of ≤ 4 on each of the following 7 PANSS items: P1, P2, P3, P6, P7, G8, and G14 at the end of Week 20 * No significant tolerability issues as judged by the Investigator During this Double-blind Treatment Phase, participants received either placebo or cariprazine at the same dosage (3, 6, or 9 mg) that they received during the last 14 weeks of the Open-label Phase. All participants entered the 4 week Safety Follow-up Phase. They received a treatment other than the investigational product at the discretion of the Investigator.
Interventions
DRUGPlacebo
Placebo was supplied in capsules.
DRUGCariprazine
Cariprazine was supplied as 1.5 mg capsules (batch numbers BN0009242 and BN00018595) and 3 mg capsules.
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
There was no masking in the Open-Label Phase. There was masking in the Double-Blind Phase
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Participants who have provided informed consent prior to any study specific procedures. * Participants currently meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR) criteria for schizophrenia. * Participants with normal physical examination, laboratory, vital signs, and/or electrocardiogram (ECG). * Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening). * Positive and Negative Syndrome Scale (PANSS) total score ≥ to 70 and ≤ 120 at Visit 1 (Screening) and Visit 2 (beginning of Run-in Phase). * Negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test (applies to female participants of childbearing potential only). * Body mass index between 18 and 40 kg/m\^2, inclusive.
Exclusion criteria
* Participants currently meeting DSM-IV-TR criteria for schizoaffective disorder, schizophreniform disorder, bipolar I and II and known or suspected borderline or antisocial personality disorder. or other DSM-IV-TR axis II disorders. * Participants in their first episode of psychosis. * Treatment-resistant schizophrenia over the last 2 years. * Positive result from the blood alcohol test or from the urine drug screen for any prohibited medication. * At imminent risk of injuring self or others or causing significant damage to property. * Suicide risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Baseline to the First Symptom Relapse During the Double-blind Phase | Up to 34 Weeks and Bi-Weekly thereafter until Week 92 | Relapse was defined as meeting ≥1 of the following criteria:1-Hospitalization due to worsening of condition;2-increase in Positive and Negative Syndrome Scale(PANSS) total score by ≥30% for participants,scored ≥50 or a ≥10-point increase for participants,scored \<50 at randomization;3-increase in Clinical Global Impressions-Severity(CGI-S) score by ≥2 points at Week 20;4-deliberate self-injury or aggressive behaviour;5-suicidal/homicidal ideation judged clinically significant by Investigator;6-score of \>4 on 1 or more of following PANSS items:P1,P2,P3,P6,P7,G8 or G14. Second assessment not performed based on Investigator discretion. PANSS is 30-item rating scale. Each item scored on 7-point scale. Total score ranges from 30 to 210. Lower score indicates fewer schizophrenic symptoms. CGI-S is 7-point scale,measures severity of participant's illness in comparison with others with same diagnosis. Lower score indicates less severe illness. 25th percentile for time to relapse was reported. |
Countries
India, Romania, Slovakia, Ukraine, United States
Participant flow
Pre-assignment details
A total of 765 participants were enrolled and received cariprazine in Run-in Phase; 751 of these, had at least 1 postbaseline Positive and Negative Syndrome Scale (PANSS) evaluation and 364 entered Stabilization Phase. Only 200 participants who completed Open-label phase, received either placebo (n=99) or cariprazine (n=101) in Double-Blind Phase.
Participants by arm
| Arm | Count |
|---|---|
| Cariprazine - Open-label Phase Participants received 3, 6, or 9 mg cariprazine orally once a day for 6 weeks; the dose could be modified during this time. The cariprazine dose was fixed at 3, 6, or 9 mg for the last 14 weeks of this 20 week Open-label Phase. | 765 |
| Total | 765 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Phase (DBP) | Adverse Event | 0 | 5 | 6 |
| Double-blind Treatment Phase (DBP) | Lost to Follow-up | 0 | 6 | 5 |
| Double-blind Treatment Phase (DBP) | Other Miscellaneous Reasons | 0 | 11 | 27 |
| Double-blind Treatment Phase (DBP) | Protocol Violation | 0 | 4 | 5 |
| Double-blind Treatment Phase (DBP) | Relapse | 0 | 47 | 25 |
| Double-blind Treatment Phase (DBP) | Withdrawal of Consent | 0 | 10 | 15 |
| Open-label Run-in Period (RIP) | Adverse Event | 86 | 0 | 0 |
| Open-label Run-in Period (RIP) | Insufficient Therapeutic Response | 66 | 0 | 0 |
| Open-label Run-in Period (RIP) | Lost to Follow-up | 32 | 0 | 0 |
| Open-label Run-in Period (RIP) | Other Miscellaneous Reasons | 19 | 0 | 0 |
| Open-label Run-in Period (RIP) | Protocol Violation | 27 | 0 | 0 |
| Open-label Run-in Period (RIP) | Withdrawal of Consent | 117 | 0 | 0 |
| Open-label Stabilization Period (SP) | Adverse Event | 9 | 0 | 0 |
| Open-label Stabilization Period (SP) | Insufficient Therapeutic Response | 9 | 0 | 0 |
| Open-label Stabilization Period (SP) | Lost to Follow-up | 9 | 0 | 0 |
| Open-label Stabilization Period (SP) | Other Miscellaneous Reasons | 19 | 0 | 0 |
| Open-label Stabilization Period (SP) | Protocol Violation | 14 | 0 | 0 |
| Open-label Stabilization Period (SP) | Withdrawal of Consent | 40 | 0 | 0 |
| Period Between RIP and SP | Adverse Event | 4 | 0 | 0 |
| Period Between RIP and SP | Insufficient Therapeutic Response | 19 | 0 | 0 |
| Period Between RIP and SP | Lost to Follow-up | 5 | 0 | 0 |
| Period Between RIP and SP | Other Miscellaneous Reasons | 23 | 0 | 0 |
| Period Between RIP and SP | Protocol Violation | 2 | 0 | 0 |
| Period Between RIP and SP | Withdrawal of Consent | 1 | 0 | 0 |
| Period Between SP and DBP | Did Not Met Criteria to Enter Next Phase | 4 | 0 | 0 |
| Period Between SP and DBP | Lost to Follow-up | 1 | 0 | 0 |
| Period Between SP and DBP | Other Miscellaneous Reasons | 55 | 0 | 0 |
| Period Between SP and DBP | Protocol Violation | 2 | 0 | 0 |
| Period Between SP and DBP | Withdrawal of Consent | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Cariprazine - Open-label Phase |
|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 10.4 |
| Body Mass Index (BMI) | 26.50 kg/m^2 STANDARD_DEVIATION 5.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 728 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 170.98 cm STANDARD_DEVIATION 9.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 149 Participants |
| Race (NIH/OMB) Black or African American | 313 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 299 Participants |
| Sex: Female, Male Female | 221 Participants |
| Sex: Female, Male Male | 544 Participants |
| Waist circumference | 90.39 cm STANDARD_DEVIATION 15.34 |
| Weight | 78.07 kg STANDARD_DEVIATION 20.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 765 | 0 / 99 | 0 / 101 | 0 / 765 | 0 / 99 | 0 / 101 |
| other Total, other adverse events | 425 / 765 | 28 / 99 | 35 / 101 | 0 / 765 | 0 / 99 | 0 / 101 |
| serious Total, serious adverse events | 50 / 765 | 14 / 99 | 14 / 101 | 6 / 765 | 2 / 99 | 0 / 101 |
Outcome results
Primary
Time From Baseline to the First Symptom Relapse During the Double-blind Phase
Relapse was defined as meeting ≥1 of the following criteria:1-Hospitalization due to worsening of condition;2-increase in Positive and Negative Syndrome Scale(PANSS) total score by ≥30% for participants,scored ≥50 or a ≥10-point increase for participants,scored \<50 at randomization;3-increase in Clinical Global Impressions-Severity(CGI-S) score by ≥2 points at Week 20;4-deliberate self-injury or aggressive behaviour;5-suicidal/homicidal ideation judged clinically significant by Investigator;6-score of \>4 on 1 or more of following PANSS items:P1,P2,P3,P6,P7,G8 or G14. Second assessment not performed based on Investigator discretion. PANSS is 30-item rating scale. Each item scored on 7-point scale. Total score ranges from 30 to 210. Lower score indicates fewer schizophrenic symptoms. CGI-S is 7-point scale,measures severity of participant's illness in comparison with others with same diagnosis. Lower score indicates less severe illness. 25th percentile for time to relapse was reported.
Time frame: Up to 34 Weeks and Bi-Weekly thereafter until Week 92
Population: Double-blind intent-to-treat population: All participants who received at least 1 dose of double-blind investigational product and who had at least 1 post-randomization assessment of PANSS or CGI-S during the Double-blind Treatment Phase.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time From Baseline to the First Symptom Relapse During the Double-blind Phase | 92 Days |
| Cariprazine | Time From Baseline to the First Symptom Relapse During the Double-blind Phase | 224 Days |
p-value: 0.00195% CI: [0.28, 0.73]Log Rank