Schizophrenia
Conditions
Brief summary
1. To evaluate the efficacy and safety of cariprazine at a target dose of 4.5 milligram per day (mg/d) compared with placebo in prevention of relapse in patients with schizophrenia 2. To evaluate the efficacy and safety of cariprazine at a target dose of 3.0 mg/d compared with placebo in prevention of relapse in patients with schizophrenia who were initially stabilized on a target dose of 4.5 mg/d
Interventions
DRUGCariprazine
Cariprazine capsules, oral administration, once daily.
DRUGPlacebo
Matching placebo capsules, oral administration, once daily.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of schizophrenia for a minimum of 1 year before Visit 1 (Screening). * Ability to follow study instructions, complete study assessment tools with minimal assistance and no alteration to the assessment tools, and likely to complete all required visits. * Participant meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia as determined by Structured Clinical Interview for DSM-5 (SCID-5). * Positive and Negative Syndrome Scale (PANSS) total score \>= 70 and \<= 120 at Visit 1 and Visit 2 (Day 1). * Rating of at least 4 (moderate) on at least 2 of the following 4 PANSS positive symptoms; P1: delusions; P2: conceptual disorganization; P3: hallucinatory behaviour; P6: suspiciousness/persecution at Visit 1 and Visit 2.
Exclusion criteria
* Currently meeting DSM-5 criteria for any of the following: * Schizoaffective disorder, schizophreniform disorder, and other psychotic disorders * Bipolar I and II disorder * Autism spectrum disorder, intellectual development disorder, delirium, major/minor neurocognitive disorder * History of meeting DSM-5 criteria for substance-related disorders (excluding caffeine-related and tobacco-related disorders) within the prior 3 months before Visit 1. * Prior participation in any clinical trials involving experimental or investigational drugs within 6 months before Visit 1 or planned during the study. * Female Participants who are pregnant, planning to become pregnant during the course of the study, or are currently lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Relapse During Double-blind Treatment Period | Randomization (Week 18) to End of Treatment (Week 44) | Time to Relapse is the number of days from randomization to first relapse. Relapse is defined as any 1 of the following: * Increase in Positive and Negative Syndrome Scale(PANSS) by ≥30% for participants who had total score of ≥50 at randomization or ≥10-point increased score with total score \<50 at randomization \[PANSS=30 questions where 1=absence of symptoms to 7=extremely severe symptom;total score=30 to 210;higher score more severe symptoms\] * Increase in Clinical Global Impression-Severity (CGI-S) score by 2 or more points \[1=normal to 7=among most extremely ill\] * Score of \>4 on 1 or more of 7 PANSS items:P1-delusions,P2-conceptual disorganization,P3-hallucinatory behavior,P6-suspiciousness,P7-hostility,G8-uncooperativeness,G14-poor impulse control * Deliberate self-injury * Initiation of treatment with mood stabilizer,antidepressant,antipsychotics or benzodiazepine that exceeds specified allowance * Psychiatric hospitalization * Exacerbation of psychiatric illness |
Countries
Bulgaria, Malaysia, Poland, Puerto Rico, Romania, Serbia, South Korea, Taiwan, Thailand, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Double-blind Treatment Period) Cariprazine placebo-matching capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period. | 53 |
| Cariprazine 3.0 mg/Day (Double-blind Treatment Period) Cariprazine 3.0 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period. | 49 |
| Cariprazine 4.5 mg/Day (Double-blind Treatment Period) Cariprazine 4.5 mg capsules orally once daily from Week 19 through Week 44 in Double-blind Treatment Period. | 54 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Treatment Period (26 Weeks) | Adverse Event | 0 | 2 | 0 | 4 |
| Double-blind Treatment Period (26 Weeks) | Lost to Follow-up | 0 | 5 | 4 | 1 |
| Double-blind Treatment Period (26 Weeks) | Non-compliance with Study Drug | 0 | 1 | 2 | 0 |
| Double-blind Treatment Period (26 Weeks) | Number of Participants with Relapse Event | 0 | 15 | 9 | 8 |
| Double-blind Treatment Period (26 Weeks) | Pregnancy | 0 | 0 | 0 | 1 |
| Double-blind Treatment Period (26 Weeks) | Protocol Deviation | 0 | 3 | 2 | 5 |
| Double-blind Treatment Period (26 Weeks) | Reason not Specified | 0 | 1 | 3 | 0 |
| Double-blind Treatment Period (26 Weeks) | Study Terminated by Sponsor | 0 | 9 | 11 | 13 |
| Double-blind Treatment Period (26 Weeks) | Withdrawal by Subject | 0 | 4 | 2 | 3 |
| Open-label Treatment Period (18 Weeks) | Adverse Event | 39 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Death | 1 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Failure to Meet Randomization Criteria | 104 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Lack of Efficacy | 14 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Lost to Follow-up | 51 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Non-compliance with Study Drug | 23 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Protocol Deviation | 5 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Reason not Specified | 13 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Study Terminated by the Sponsor | 90 | 0 | 0 | 0 |
| Open-label Treatment Period (18 Weeks) | Withdrawal by Subject | 85 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cariprazine 4.5 mg/Day (Double-blind Treatment Period) | Total | Placebo (Double-blind Treatment Period) | Cariprazine 3.0 mg/Day (Double-blind Treatment Period) |
|---|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 11.08 | 41.7 years STANDARD_DEVIATION 10.92 | 41.7 years STANDARD_DEVIATION 10.94 | 40.6 years STANDARD_DEVIATION 10.84 |
| Race/Ethnicity, Customized Hispanic | 10 Participants | 32 Participants | 10 Participants | 12 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 44 Participants | 124 Participants | 43 Participants | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 111 Participants | 34 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 39 Participants | 17 Participants | 11 Participants |
| Sex: Female, Male Female | 22 Participants | 53 Participants | 14 Participants | 17 Participants |
| Sex: Female, Male Male | 32 Participants | 103 Participants | 39 Participants | 32 Participants |
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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 587 | 0 / 273 | 0 / 54 | 0 / 49 | 0 / 56 | 0 / 54 | 0 / 49 | 0 / 56 |
| other Total, other adverse events | 83 / 587 | 0 / 273 | 5 / 53 | 9 / 49 | 3 / 54 | 0 / 53 | 1 / 49 | 0 / 54 |
| serious Total, serious adverse events | 20 / 587 | 7 / 273 | 5 / 53 | 0 / 49 | 1 / 54 | 0 / 53 | 0 / 49 | 2 / 54 |
Outcome results
Primary
Time to First Relapse During Double-blind Treatment Period
Time to Relapse is the number of days from randomization to first relapse. Relapse is defined as any 1 of the following: * Increase in Positive and Negative Syndrome Scale(PANSS) by ≥30% for participants who had total score of ≥50 at randomization or ≥10-point increased score with total score \<50 at randomization \[PANSS=30 questions where 1=absence of symptoms to 7=extremely severe symptom;total score=30 to 210;higher score more severe symptoms\] * Increase in Clinical Global Impression-Severity (CGI-S) score by 2 or more points \[1=normal to 7=among most extremely ill\] * Score of \>4 on 1 or more of 7 PANSS items:P1-delusions,P2-conceptual disorganization,P3-hallucinatory behavior,P6-suspiciousness,P7-hostility,G8-uncooperativeness,G14-poor impulse control * Deliberate self-injury * Initiation of treatment with mood stabilizer,antidepressant,antipsychotics or benzodiazepine that exceeds specified allowance * Psychiatric hospitalization * Exacerbation of psychiatric illness
Time frame: Randomization (Week 18) to End of Treatment (Week 44)
Population: The Double-blind Intent-to Treat (DB ITT) population included all participants in the DB safety population who had at least 1 post-randomization assessment of the PANSS or CGI-S scores during the DB treatment period of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Double-blind Treatment Period) | Time to First Relapse During Double-blind Treatment Period | NA days |
| Cariprazine 3.0 mg/Day (Double-blind Treatment Period) | Time to First Relapse During Double-blind Treatment Period | NA days |
| Cariprazine 4.5 mg/Day (Double-blind Treatment Period) | Time to First Relapse During Double-blind Treatment Period | NA days |
p-value: =0.157695% CI: [0.25, 1.29]Log Rank
p-value: =0.206695% CI: [0.26, 1.45]Log Rank