Trial Outcomes & Findings for Safety and Efficacy of Cariprazine for Mania (NCT NCT01058096)
NCT ID: NCT01058096
Last Updated: 2017-04-17
Results Overview
The YMRS is an 11-item scale that assesses manic symptoms based on the participant's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11-items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of the abnormality for 7-items are rated on a 5-point scale (0-4) and 4-items on a 9-point scale (0-8). The individual scores are summed for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Analysis was a mixed model for repeated measurements (MMRM) observed cases (OC), with treatment group, pooled study center, visit, treatment group-by-visit interaction as factors, baseline value and baseline-by-visit interaction as covariates and an unstructured covariance matrix.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
323 participants
Primary outcome timeframe
Baseline, Week 3
Results posted on
2017-04-17
Participant Flow
11 participants from 1 investigational site are not included in the analyses due to Good Clinical Practice (GCP) violations.
Participant milestones
| Measure |
Placebo
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine
Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|
|
Double-blind Treatment Phase
STARTED
|
154
|
158
|
|
Double-blind Treatment Phase
COMPLETED
|
106
|
108
|
|
Double-blind Treatment Phase
NOT COMPLETED
|
48
|
50
|
|
Safety Follow-up
STARTED
|
133
|
134
|
|
Safety Follow-up
COMPLETED
|
129
|
130
|
|
Safety Follow-up
NOT COMPLETED
|
4
|
4
|
Reasons for withdrawal
| Measure |
Placebo
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine
Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|
|
Double-blind Treatment Phase
Adverse Event
|
11
|
15
|
|
Double-blind Treatment Phase
Insufficient Therapeutic Response
|
16
|
7
|
|
Double-blind Treatment Phase
Protocol Violation
|
2
|
1
|
|
Double-blind Treatment Phase
Withdrawal of Consent
|
17
|
26
|
|
Double-blind Treatment Phase
Lost to Follow-up
|
0
|
1
|
|
Double-blind Treatment Phase
Other Unspecified
|
2
|
0
|
Baseline Characteristics
Safety and Efficacy of Cariprazine for Mania
Baseline characteristics by cohort
| Measure |
Placebo
n=154 Participants
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine
n=158 Participants
Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
Total
n=312 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.7 years
STANDARD_DEVIATION 11.8 • n=93 Participants
|
35.8 years
STANDARD_DEVIATION 11.4 • n=4 Participants
|
36.3 years
STANDARD_DEVIATION 11.5 • n=27 Participants
|
|
Sex: Female, Male
Female
|
59 Participants
n=93 Participants
|
53 Participants
n=4 Participants
|
112 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
95 Participants
n=93 Participants
|
105 Participants
n=4 Participants
|
200 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
149 Participants
n=93 Participants
|
153 Participants
n=4 Participants
|
302 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
33 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
66 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
29 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
62 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
88 Participants
n=93 Participants
|
91 Participants
n=4 Participants
|
179 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Weight
|
71.86 kilogram (kg)
STANDARD_DEVIATION 20.27 • n=93 Participants
|
69.55 kilogram (kg)
STANDARD_DEVIATION 20.06 • n=4 Participants
|
70.69 kilogram (kg)
STANDARD_DEVIATION 20.17 • n=27 Participants
|
|
Height
|
166.39 centimeter (cm)
STANDARD_DEVIATION 10.64 • n=93 Participants
|
165.21 centimeter (cm)
STANDARD_DEVIATION 10.68 • n=4 Participants
|
165.79 centimeter (cm)
STANDARD_DEVIATION 10.66 • n=27 Participants
|
|
Body Mass Index (BMI)
|
25.73 kg/meter(m)^2
STANDARD_DEVIATION 5.98 • n=93 Participants
|
25.24 kg/meter(m)^2
STANDARD_DEVIATION 5.98 • n=4 Participants
|
25.48 kg/meter(m)^2
STANDARD_DEVIATION 5.98 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 3Population: Intent-to-treat Population included all participants who received at least 1 dose of study drug and who had at least 1 post-baseline YMRS assessment.
The YMRS is an 11-item scale that assesses manic symptoms based on the participant's perception of his or her condition over the previous 48 hours, as well as the physician's clinical observations during the interview. The 11-items are elevated mood, increased motor activity-energy, sexual interest, sleep, irritability, rate and amount of speech, language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. The severity of the abnormality for 7-items are rated on a 5-point scale (0-4) and 4-items on a 9-point scale (0-8). The individual scores are summed for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Analysis was a mixed model for repeated measurements (MMRM) observed cases (OC), with treatment group, pooled study center, visit, treatment group-by-visit interaction as factors, baseline value and baseline-by-visit interaction as covariates and an unstructured covariance matrix.
Outcome measures
| Measure |
Placebo
n=152 Participants
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine
n=158 Participants
Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3
|
-15.3 score on a scale
Standard Error 0.9
|
-19.6 score on a scale
Standard Error 0.9
|
SECONDARY outcome
Timeframe: Baseline, Week 3Population: Intent-to-treat Population included all participants who received at least 1 dose of study drug and who had at least 1 post-baseline YMRS assessment.
The CGI-S measures the investigator's assessment of overall severity of the participant's illness compared with the severity of illness in other patients the physician has observed using a 7-point scale (1=Normal, not ill at all to 7=Among the most extremely ill participants). A negative change from Baseline indicates improvement. Analysis was based on a MMRM using the observed cases (OC) data, with treatment group, pooled study center, visit, treatment group-by-visit interaction as factors, baseline value and baseline-by-visit interaction as covariates and an unstructured covariance matrix.
Outcome measures
| Measure |
Placebo
n=152 Participants
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine
n=158 Participants
Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|
|
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3
|
-1.3 score on a scale
Standard Error 0.1
|
-1.6 score on a scale
Standard Error 0.1
|
Adverse Events
Placebo
Serious events: 5 serious events
Other events: 69 other events
Deaths: 0 deaths
Cariprazine
Serious events: 6 serious events
Other events: 110 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=154 participants at risk
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine
n=158 participants at risk
Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|
|
Psychiatric disorders
Mania
|
0.65%
1/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
1.9%
3/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Akathisia
|
0.00%
0/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
0.63%
1/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Convulsion
|
0.00%
0/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
0.63%
1/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
0.63%
1/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Infections and infestations
Hepatitis E
|
0.65%
1/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
0.00%
0/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Social circumstances
Social stay hospitalisation
|
0.65%
1/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
0.00%
0/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Bipolar disorder
|
0.65%
1/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
0.00%
0/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
General disorders
Non-cardiac chest pain
|
0.65%
1/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
0.00%
0/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
Other adverse events
| Measure |
Placebo
n=154 participants at risk
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine
n=158 participants at risk
Cariprazine 3 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
4.5%
7/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
10.8%
17/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Nausea
|
6.5%
10/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
10.1%
16/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
7/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
10.1%
16/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Constipation
|
6.5%
10/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
8.9%
14/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.9%
6/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
7.0%
11/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
3.9%
6/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
5.1%
8/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
General disorders
Pyrexia
|
3.2%
5/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
5.7%
9/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Akathisia
|
5.2%
8/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
22.2%
35/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Extrapyramidal Disorder
|
1.9%
3/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
15.2%
24/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Tremor
|
5.8%
9/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
12.0%
19/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Headache
|
10.4%
16/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
11.4%
18/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Dizziness
|
3.9%
6/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
8.9%
14/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Nervous system disorders
Somnolence
|
1.3%
2/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
6.3%
10/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Restlessness
|
0.65%
1/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
6.3%
10/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
|
Psychiatric disorders
Insomnia
|
5.2%
8/154 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
5.7%
9/158 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all randomized participants who took at least 1 dose of double-blind investigational product.
|
Additional Information
Therapeutic Area Head
Allergan, Inc.
Phone: 714-246-4500
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