Safety and Efficacy of Cariprazine in Patients With Schizophrenia

Conditions

Schizophrenia

Keywords

Schizophrenia, Acute Schizophrenia, Psychotropic Drugs, Aripiprazole, 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.

Peter Falkai, R. Csehi, K. Acsai, György Németh

European Psychiatry2024-04-01

10.1192/j.eurpsy.2024.453

Cariprazine’s efficacy in treating depressive symptoms – pooled data from schizophrenia, bipolar depression and major depression trials

Roger S. McIntyre, Réka Csehi, György Németh

European Psychiatry2023-03-011 citations

10.1192/j.eurpsy.2023.664

Cariprazine’s efficacy in treating affective symptoms – pooled data from schizophrenia and bipolar depression trials

R. W. McIntyre, Z.B. Dombi, Á. Barabássy, G. Németh

European Psychiatry2022-06-01

10.1192/j.eurpsy.2022.419

Benzodiazepine use during cariprazine treatment in acute schizophrenia

Christoph U. Correll, B. Sebe, R. Csehi, K. Acsai, Á. Barabássy

European Psychiatry2022-06-01

10.1192/j.eurpsy.2022.283

Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety.

Laszlovszky I, Barabássy Á, Németh G.

2021-06-0649 citations

10.1007/s12325-021-01797-5

Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies

Ágota Barabássy, B. Sebe, K. Acsai, I. Laszlovszky, B. Szatmári et al. (7 authors)

Neuropsychiatric Disease and Treatment2021-04-0142 citations

10.2147/ndt.s301225

Tolerability of cariprazine in the early stage of schizophrenia: A pooled, post-hoc analysis of 4 phase ii/iii double-blind placebo-controlled trials

Z.B. Dombi, K. Acsai, Ágota Barabássy, B. Sebe, I. Laszlovszky et al. (10 authors)

European Psychiatry2021-04-01

10.1192/j.eurpsy.2021.1400

Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies

Stephen R. Marder, W. Wolfgang Fleischhacker, Willie Earley, Kaifeng Lu, Yan Zhong et al. (9 authors)

European Neuropsychopharmacology2018-11-2049 citations

10.1016/j.euroneuro.2018.10.008

Efficacy of cariprazine on negative symptoms in patients with acute schizophrenia: A post hoc analysis of pooled data

Willie Earley, Hua Guo, David G. Daniel, Henry A. Nasrallah, Suresh Durgam et al. (10 authors)

Schizophrenia Research2018-08-2965 citations

10.1016/j.schres.2018.08.020

Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia

Willie Earley, Suresh Durgam, Kaifeng Lu, I. Laszlovszky, M. Debelle et al. (6 authors)

International Clinical Psychopharmacology2017-07-0758 citations

10.1097/yic.0000000000000187

Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study.

Cutler AJ, Durgam S, Wang Y, Migliore R, Lu K, Laszlovszky I, Németh G.

2017-05-0841 citations

10.1017/s1092852917000220

105. Efficacy of Cariprazine in Patients With Schizophrenia Based on Stage of Illness

Ricky Mofsen, Cheng-Tao Cheng, György Németh, Ágota Barabássy, Willie Earley

Schizophrenia Bulletin2017-03-01

10.1093/schbul/sbx021.143

The Effect of Cariprazine on Hostility Associated With Schizophrenia

Leslie Citrome, Suresh Durgam, Kaifeng Lu, Paul Ferguson, I. Laszlovszky

The Journal of Clinical Psychiatry2016-01-2540 citations

10.4088/jcp.15m10192

Cariprazine in Acute Exacerbation of Schizophrenia

Suresh Durgam, Andrew J. Cutler, Kaifeng Lu, Raffaele Migliore, Adam Ruth et al. (8 authors)

The Journal of Clinical Psychiatry2015-12-21164 citations

10.4088/jcp.15m09997

Cariprazine in Negative Symptoms of Schizophrenia: Post-hoc Analyses of a Fixed-dose Phase Iii, Randomized, Double-blind, Placebo- and Active-controlled Trial

M. Debelle, S. Faradzs-zade, B. Szatmári, Krisztián Nagy, György Németh et al. (7 authors)

European Psychiatry2015-03-016 citations

10.1016/s0924-9338(15)30197-8

EPA-0870 – Efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia: results of two phase III trials

I. Laszlovszky, Kaifeng Lu, M. Debelle, Suresh Durgam

European Psychiatry2014-01-012 citations

10.1016/s0924-9338(14)78201-x

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.

DRUGAripiprazole

Patients who meet eligibility criteria will be administered a once daily oral dose of aripiprazole 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.

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) * Patients with normal physical examination, laboratory, vital signs,and/ or electrocardiogram (ECG) * Current psychotic episode (schizophrenia exacerbation) \< 2 weeks duration at Visit 1 * Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCIPANSS) total score ≥ 80 and ≤ 120 * CGI-S score ≥ 4

Exclusion criteria

* Schizoaffective disorder, schizophreniform disorder, and other psychotic disorders * Bipolar I and II disorder * Pervasive developmental disorder, mental retardation, delirium, dementia, amnestic and other cognitive disorders * DSM-IV-TR axis II disorder of sufficient severity to interfere with participation in this study * Women who are pregnant or breast feeding

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 from baseline score indicates improvement.

Secondary

Measure	Time frame	Description
Measurement of the Overall Severity of Illness: 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 from baseline score indicates improvement.

Countries

Romania, Russia, Ukraine, 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.	153
Cariprazine 3.0 mg Oral administration. Once per day.	155
Cariprazine 6.0mg Oral administration. Once per day.	157
Aripiprazole 10.0 mg Oral administration. Once per day.	152
Total	617

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	17	15	20	14
Overall Study	Did not meet inc/exc criteria	1	0	0	0
Overall Study	Lack of Efficacy	20	15	14	8
Overall Study	Lost to Follow-up	1	2	1	1
Overall Study	Protocol Violation	2	0	0	0
Overall Study	Withdrawal by Subject	17	19	25	15

Baseline characteristics

Characteristic	Cariprazine 3.0 mg	Aripiprazole 10.0 mg	Total	Placebo	Cariprazine 6.0mg
Age, Continuous	37.9 Years STANDARD_DEVIATION 10.6	39.3 Years STANDARD_DEVIATION 10.8	38.5 Years STANDARD_DEVIATION 10.8	38.2 Years STANDARD_DEVIATION 11.3	38.6 Years STANDARD_DEVIATION 10.6
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	2 Participants	12 Participants	3 Participants	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	134 Participants	134 Participants	538 Participants	137 Participants	133 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	19 Participants	16 Participants	67 Participants	13 Participants	19 Participants
Race/Ethnicity, Customized Asian	1 Participants	2 Participants	4 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Black or African-American	32 Participants	33 Participants	143 Participants	42 Participants	36 Participants
Race/Ethnicity, Customized Missing	17 Participants	16 Participants	62 Participants	12 Participants	17 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	5 Participants	3 Participants	0 Participants
Race/Ethnicity, Customized Other	2 Participants	1 Participants	8 Participants	2 Participants	3 Participants
Race/Ethnicity, Customized White	102 Participants	99 Participants	395 Participants	93 Participants	101 Participants
Sex/Gender, Customized Female	56 Participants	58 Participants	227 Participants	56 Participants	57 Participants
Sex/Gender, Customized Male	99 Participants	94 Participants	390 Participants	97 Participants	100 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 / 153	0 / 155	2 / 157	0 / 152
other Total, other adverse events	68 / 153	61 / 155	71 / 157	61 / 152
serious Total, serious adverse events	2 / 153	4 / 155	7 / 157	4 / 152

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 from baseline 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.	-14.3 Units on a Scale	Standard Error 1.5
Cariprazine 3.0 mg	Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score.	-20.2 Units on a Scale	Standard Error 1.5
Cariprazine 6.0mg	Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score.	-23.0 Units on a Scale	Standard Error 1.5
Aripiprazole 10.0 mg	Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score.	-21.2 Units on a Scale	Standard Error 1.4

p-value: 0.004495% CI: [-10.1, -1.9]ANCOVA

p-value: <0.000195% CI: [-12.9, -4.7]ANCOVA

p-value: 0.000895% CI: [-11, -2.9]ANCOVA

Secondary

Measurement of the Overall Severity of Illness: 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 from baseline 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 the Overall Severity of Illness: Change From Baseline in Clinical Global Impression-Severity (CGI-S)	-1.0 Units on a Scale	Standard Error 0.1
Cariprazine 3.0 mg	Measurement of the Overall Severity of Illness: Change From Baseline in Clinical Global Impression-Severity (CGI-S)	-1.4 Units on a Scale	Standard Error 0.1
Cariprazine 6.0mg	Measurement of the Overall Severity of Illness: Change From Baseline in Clinical Global Impression-Severity (CGI-S)	-1.5 Units on a Scale	Standard Error 0.1
Aripiprazole 10.0 mg	Measurement of the Overall Severity of Illness: Change From Baseline in Clinical Global Impression-Severity (CGI-S)	-1.4 Units on a Scale	Standard Error 0.1

p-value: 0.000495% CI: [-0.6, -0.2]ANCOVA

p-value: <0.000195% CI: [-0.7, -0.3]ANCOVA

p-value: 0.000195% CI: [-0.6, -0.2]ANCOVA

Safety and Efficacy of Cariprazine in Patients With Schizophrenia

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Measurement of Schizophrenia Symptoms: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score.

Measurement of the Overall Severity of Illness: Change From Baseline in Clinical Global Impression-Severity (CGI-S)