Trial Outcomes & Findings for Safety and Efficacy of Cariprazine for Bipolar I Disorder (NCT NCT01058668)
NCT ID: NCT01058668
Last Updated: 2017-04-12
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 five-point scale (0-4) and 4-items on a nine-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 is a mixed model for repeated measurements (MMRM) using observed cases, 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
497 participants
Primary outcome timeframe
Baseline, Week 3
Results posted on
2017-04-12
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine (3-6 mg/Day)
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
|
Cariprazine (6-12 mg/Day)
Cariprazine 6 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|---|
|
Double-blind Treatment Phase
STARTED
|
161
|
167
|
169
|
|
Double-blind Treatment Phase
COMPLETED
|
122
|
129
|
119
|
|
Double-blind Treatment Phase
NOT COMPLETED
|
39
|
38
|
50
|
|
Safety Follow-up
STARTED
|
144
|
146
|
148
|
|
Safety Follow-up
COMPLETED
|
139
|
146
|
141
|
|
Safety Follow-up
NOT COMPLETED
|
5
|
0
|
7
|
Reasons for withdrawal
| Measure |
Placebo
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine (3-6 mg/Day)
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
|
Cariprazine (6-12 mg/Day)
Cariprazine 6 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|---|
|
Double-blind Treatment Phase
Adverse Event
|
8
|
15
|
25
|
|
Double-blind Treatment Phase
Insufficient Therapeutic Response
|
15
|
2
|
5
|
|
Double-blind Treatment Phase
Protocol Violation
|
1
|
1
|
2
|
|
Double-blind Treatment Phase
Withdrawal of Consent
|
14
|
18
|
17
|
|
Double-blind Treatment Phase
Lost to Follow-up
|
0
|
1
|
1
|
|
Double-blind Treatment Phase
Other Unspecified
|
1
|
1
|
0
|
Baseline Characteristics
Safety and Efficacy of Cariprazine for Bipolar I Disorder
Baseline characteristics by cohort
| Measure |
Placebo
n=161 Participants
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine (3-6 mg/Day)
n=167 Participants
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
|
Cariprazine (6-12 mg/Day)
n=169 Participants
Cariprazine 6 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
Total
n=497 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
41.5 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
43.1 years
STANDARD_DEVIATION 12.2 • n=7 Participants
|
41.2 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
41.9 years
STANDARD_DEVIATION 11.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
72 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
233 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
89 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
85 Participants
n=5 Participants
|
264 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
151 Participants
n=5 Participants
|
157 Participants
n=7 Participants
|
165 Participants
n=5 Participants
|
473 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
|
114 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
345 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
44 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
139 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Weight
|
81.70 kilogram (kg)
STANDARD_DEVIATION 15.96 • n=5 Participants
|
82.42 kilogram (kg)
STANDARD_DEVIATION 16.22 • n=7 Participants
|
81.49 kilogram (kg)
STANDARD_DEVIATION 16.78 • n=5 Participants
|
81.87 kilogram (kg)
STANDARD_DEVIATION 16.30 • n=4 Participants
|
|
Height
|
170.93 centimeter (cm)
STANDARD_DEVIATION 9.88 • n=5 Participants
|
170.99 centimeter (cm)
STANDARD_DEVIATION 9.15 • n=7 Participants
|
170.25 centimeter (cm)
STANDARD_DEVIATION 9.36 • n=5 Participants
|
170.72 centimeter (cm)
STANDARD_DEVIATION 9.45 • n=4 Participants
|
|
Body Mass Index (BMI)
|
27.99 kg/meter(m)^2
STANDARD_DEVIATION 5.15 • n=5 Participants
|
28.22 kg/meter(m)^2
STANDARD_DEVIATION 5.29 • n=7 Participants
|
28.04 kg/meter(m)^2
STANDARD_DEVIATION 4.92 • n=5 Participants
|
28.08 kg/meter(m)^2
STANDARD_DEVIATION 5.12 • n=4 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 five-point scale (0-4) and 4-items on a nine-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 is a mixed model for repeated measurements (MMRM) using observed cases, 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=160 Participants
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine (3-6 mg/Day)
n=165 Participants
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
|
Cariprazine (6-12 mg/Day)
n=167 Participants
Cariprazine 6 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
|
-12.5 score on a scale
Standard Error 0.8
|
-18.6 score on a scale
Standard Error 0.8
|
-18.5 score on a scale
Standard Error 0.8
|
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 is based on a MMRM using the observed cases 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=160 Participants
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine (3-6 mg/Day)
n=165 Participants
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
|
Cariprazine (6-12 mg/Day)
n=167 Participants
Cariprazine 6 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
|
-1.9 score on a scale
Standard Error 0.1
|
-1.9 score on a scale
Standard Error 0.1
|
Adverse Events
Placebo
Serious events: 5 serious events
Other events: 63 other events
Deaths: 0 deaths
Cariprazine (3-6 mg/Day)
Serious events: 9 serious events
Other events: 89 other events
Deaths: 0 deaths
Cariprazine (6-12 mg/Day)
Serious events: 5 serious events
Other events: 90 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=161 participants at risk
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine (3-6 mg/Day)
n=167 participants at risk
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
|
Cariprazine (6-12 mg/Day)
n=169 participants at risk
Cariprazine 6 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|---|
|
Psychiatric disorders
Mania
|
1.9%
3/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
1.8%
3/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
1.8%
3/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Bipolar disorder
|
0.62%
1/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.60%
1/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.00%
0/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Aggression
|
0.00%
0/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.60%
1/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.00%
0/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.60%
1/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.00%
0/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Surgical and medical procedures
Hospitalisation
|
0.00%
0/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.60%
1/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.00%
0/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.60%
1/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.00%
0/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Bipolar I disorder
|
0.62%
1/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.60%
1/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.59%
1/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Depression
|
0.00%
0/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.00%
0/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
0.59%
1/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Placebo
n=161 participants at risk
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
|
Cariprazine (3-6 mg/Day)
n=167 participants at risk
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
|
Cariprazine (6-12 mg/Day)
n=169 participants at risk
Cariprazine 6 mg - 12 mg capsules oral administration, once per day for 3 weeks.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.6%
9/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
9.6%
16/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
11.2%
19/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
3.1%
5/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
4.8%
8/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
10.7%
18/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
10/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
9.0%
15/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
8.3%
14/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Dyspepsia
|
3.1%
5/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
4.2%
7/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
5.9%
10/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.5%
12/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
2.4%
4/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
5.3%
9/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Akathisia
|
5.0%
8/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
17.4%
29/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
22.5%
38/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
9.3%
15/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
11.4%
19/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
11.8%
20/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Extrapyramidal disorder
|
5.0%
8/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
9.6%
16/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
7.1%
12/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Tremor
|
1.9%
3/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
2.4%
4/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
5.9%
10/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Nervous system disorders
Dizziness
|
2.5%
4/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
5.4%
9/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
4.1%
7/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Insomnia
|
9.3%
15/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
9.6%
16/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
10.1%
17/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
|
Psychiatric disorders
Restlessness
|
5.0%
8/161 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
9.0%
15/167 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
5.9%
10/169 • First dose of study drug to 30 days past last dose (Up to 51 days)
Safety Population included all participants who received at least 1 dose of study drug.
|
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