Trial Outcomes & Findings for Safety and Efficacy of Cariprazine in Schizophrenia (NCT NCT01104779)
NCT ID: NCT01104779
Last Updated: 2018-11-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
446 participants
Primary outcome timeframe
Baseline to Week 6
Results posted on
2018-11-14
Participant Flow
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.
Participant milestones
| Measure |
Placebo
Oral administration. Once per day.
|
Cariprazine (3-6 mg/Day)
Oral administration. Once per day.
|
Cariprazine (6-9 mg/Day)
Oral administration. Once per day.
|
|---|---|---|---|
|
Overall Study
STARTED
|
147
|
151
|
148
|
|
Overall Study
COMPLETED
|
88
|
96
|
86
|
|
Overall Study
NOT COMPLETED
|
59
|
55
|
62
|
Reasons for withdrawal
| Measure |
Placebo
Oral administration. Once per day.
|
Cariprazine (3-6 mg/Day)
Oral administration. Once per day.
|
Cariprazine (6-9 mg/Day)
Oral administration. Once per day.
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
2
|
2
|
|
Overall Study
Lack of Efficacy
|
26
|
12
|
13
|
|
Overall Study
Adverse Event
|
13
|
14
|
13
|
|
Overall Study
Did not meet inc/exc criteria
|
1
|
1
|
1
|
|
Overall Study
Other reasons
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
16
|
25
|
32
|
Baseline Characteristics
Safety and Efficacy of Cariprazine in Schizophrenia
Baseline characteristics by cohort
| Measure |
Placebo
n=147 Participants
Oral administration. Once per day.
|
Cariprazine (3-6 mg/Day)
n=151 Participants
Oral administration. Once per day.
|
Cariprazine (6-9 mg/Day)
n=148 Participants
Oral administration. Once per day.
|
Total
n=446 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
36.7 Years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
36.6 Years
STANDARD_DEVIATION 10.5 • n=7 Participants
|
35.5 Years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
36.3 Years
STANDARD_DEVIATION 10.4 • n=4 Participants
|
|
Sex/Gender, Customized
Male
|
110 Participants
n=5 Participants
|
118 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
341 Participants
n=4 Participants
|
|
Sex/Gender, Customized
Female
|
37 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
105 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
74 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
124 Participants
n=5 Participants
|
127 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
372 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
26 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
84 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African-American
|
51 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
160 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
56 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
168 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 6Population: Intent-to-Treat Population, consisting of all patients in the Safety Population who had at least one postbaseline assessment of the 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.
Outcome measures
| Measure |
Placebo
n=145 Participants
Oral administration. Once per day.
|
Cariprazine (3-6 mg/Day)
n=147 Participants
Oral administration. Once per day.
|
Cariprazine (6-9 mg/Day)
n=147 Participants
Oral administration. Once per day.
|
|---|---|---|---|
|
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
|
-22.8 Units on a Scale
Standard Error 1.6
|
-25.9 Units on a Scale
Standard Error 1.7
|
SECONDARY outcome
Timeframe: Baseline to Week 6Population: Intent-to-Treat Population, consisting of all patients in the Safety Population who had at least one postbaseline assessment of the PANSS total score.
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.
Outcome measures
| Measure |
Placebo
n=145 Participants
Oral administration. Once per day.
|
Cariprazine (3-6 mg/Day)
n=147 Participants
Oral administration. Once per day.
|
Cariprazine (6-9 mg/Day)
n=147 Participants
Oral administration. Once per day.
|
|---|---|---|---|
|
Measurement of Schizophrenia Symptoms: Change From Baseline in Clinical Global Impression-Severity (CGI-S)
|
-1.0 units on a scale
Standard Error 0.1
|
-1.4 units on a scale
Standard Error 0.1
|
-1.6 units on a scale
Standard Error 0.1
|
Adverse Events
Placebo
Serious events: 13 serious events
Other events: 54 other events
Deaths: 0 deaths
Cariprazine (3-6 mg/Day)
Serious events: 9 serious events
Other events: 84 other events
Deaths: 0 deaths
Cariprazine (6-9 mg/Day)
Serious events: 4 serious events
Other events: 86 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=147 participants at risk；n=161 participants at risk
Oral administration. Once per day.
|
Cariprazine (3-6 mg/Day)
n=151 participants at risk；n=167 participants at risk
Oral administration. Once per day.
|
Cariprazine (6-9 mg/Day)
n=148 participants at risk；n=169 participants at risk
Oral administration. Once per day.
|
|---|---|---|---|
|
Psychiatric disorders
Psychotic disorder
|
1.2%
2/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
2.4%
4/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.59%
1/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.59%
1/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Investigations
Blood pressure increased
|
0.00%
0/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.59%
1/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Investigations
Heart rate irregular
|
0.00%
0/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.59%
1/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.59%
1/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Psychomotor hyperactivity
|
1.9%
3/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
1.8%
3/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Schizophrenia
|
3.7%
6/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
1.2%
2/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.62%
1/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.60%
1/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Anxiety
|
0.62%
1/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Polydipsia psychogenic
|
0.62%
1/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Schizophrenia, paranoid type
|
0.62%
1/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Suicidal ideation
|
0.62%
1/161 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/167 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
0.00%
0/169 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
Other adverse events
| Measure |
Placebo
n=147 participants at risk；n=161 participants at risk
Oral administration. Once per day.
|
Cariprazine (3-6 mg/Day)
n=151 participants at risk；n=167 participants at risk
Oral administration. Once per day.
|
Cariprazine (6-9 mg/Day)
n=148 participants at risk；n=169 participants at risk
Oral administration. Once per day.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.8%
7/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
4.6%
7/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
9.5%
14/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Constipation
|
3.4%
5/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
9.3%
14/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
6.8%
10/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Dyspepsia
|
4.1%
6/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
2.0%
3/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
6.8%
10/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Vomiting
|
2.7%
4/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
5.3%
8/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
5.4%
8/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.4%
2/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
5.3%
8/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
4.1%
6/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Investigations
Weight increased
|
1.4%
2/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
3.3%
5/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
5.4%
8/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Akathisia
|
3.4%
5/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
15.9%
24/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
16.9%
25/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Headache
|
12.9%
19/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
9.3%
14/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
16.2%
24/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Extrapyramidal disorder
|
2.7%
4/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
5.3%
8/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
10.1%
15/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Tremor
|
2.0%
3/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
7.9%
12/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
5.4%
8/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Insomnia
|
10.9%
16/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
6.6%
10/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
10.8%
16/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Restlessness
|
4.8%
7/147 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
6.6%
10/151 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
10.1%
15/148 • Adverse Events were collected for 8 weeks.
Safety Population: All patients in the randomized population who took at least 1 dose of double-blind investigational product.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
- Publication restrictions are in place
Restriction type: OTHER