Bipolar I Disorder, Mania
Conditions
Keywords
Acute Mania, Bipolar I Disorder
Brief summary
The objective of this study is to evaluate the efficacy, safety, and tolerability of cariprazine monotherapy versus placebo for the treatment of acute manic or mixed episodes associated with bipolar I disorder.
Interventions
DRUGCariprazine
Patients who meet eligibility criteria will be administered a once daily oral dose of cariprazine for three 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 three weeks.
Sponsors
Gedeon Richter Ltd.
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 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 bipolar I disorder, as confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID) manic or mixed type with or without psychotic symptoms * Voluntarily hospitalized for current manic episode * Patients with normal physical examination, laboratory, vital signs,and/ or electrocardiogram (ECG)
Exclusion criteria
* Patients with a DSM-IV-TR diagnosis of an axis I disorder other than bipolar I disorder that was the primary focus of treatment within the previous six months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3 | Baseline, Week 3 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3 | Baseline, Week 3 | 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. |
Countries
Croatia, Romania, Russia, Serbia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks. | 161 |
| Cariprazine (3-6 mg/Day) Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks. | 167 |
| Cariprazine (6-12 mg/Day) Cariprazine 6 mg - 12 mg capsules oral administration, once per day for 3 weeks. | 169 |
| Total | 497 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Treatment Phase | Adverse Event | 8 | 15 | 25 |
| Double-blind Treatment Phase | Insufficient Therapeutic Response | 15 | 2 | 5 |
| Double-blind Treatment Phase | Lost to Follow-up | 0 | 1 | 1 |
| Double-blind Treatment Phase | Other Unspecified | 1 | 1 | 0 |
| Double-blind Treatment Phase | Protocol Violation | 1 | 1 | 2 |
| Double-blind Treatment Phase | Withdrawal of Consent | 14 | 18 | 17 |
Baseline characteristics
| Characteristic | Placebo | Total | Cariprazine (6-12 mg/Day) | Cariprazine (3-6 mg/Day) |
|---|---|---|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 11.4 | 41.9 years STANDARD_DEVIATION 11.7 | 41.2 years STANDARD_DEVIATION 11.3 | 43.1 years STANDARD_DEVIATION 12.2 |
| Body Mass Index (BMI) | 27.99 kg/meter(m)^2 STANDARD_DEVIATION 5.15 | 28.08 kg/meter(m)^2 STANDARD_DEVIATION 5.12 | 28.04 kg/meter(m)^2 STANDARD_DEVIATION 4.92 | 28.22 kg/meter(m)^2 STANDARD_DEVIATION 5.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 24 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 151 Participants | 473 Participants | 165 Participants | 157 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 170.93 centimeter (cm) STANDARD_DEVIATION 9.88 | 170.72 centimeter (cm) STANDARD_DEVIATION 9.45 | 170.25 centimeter (cm) STANDARD_DEVIATION 9.36 | 170.99 centimeter (cm) STANDARD_DEVIATION 9.15 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 5 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black/African American | 44 Participants | 139 Participants | 51 Participants | 44 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 114 Participants | 345 Participants | 114 Participants | 117 Participants |
| Sex: Female, Male Female | 72 Participants | 233 Participants | 84 Participants | 77 Participants |
| Sex: Female, Male Male | 89 Participants | 264 Participants | 85 Participants | 90 Participants |
| Weight | 81.70 kilogram (kg) STANDARD_DEVIATION 15.96 | 81.87 kilogram (kg) STANDARD_DEVIATION 16.3 | 81.49 kilogram (kg) STANDARD_DEVIATION 16.78 | 82.42 kilogram (kg) STANDARD_DEVIATION 16.22 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 161 | 89 / 167 | 90 / 169 |
| serious Total, serious adverse events | 5 / 161 | 9 / 167 | 5 / 169 |
Outcome results
Primary
Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3
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.
Time frame: Baseline, Week 3
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Cariprazine (3-6 mg/Day) | Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3 | -18.6 score on a scale | Standard Error 0.8 |
| Cariprazine (6-12 mg/Day) | Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3 | -18.5 score on a scale | Standard Error 0.8 |
p-value: <0.00195% CI: [-8.4, -3.8]Mixed Models Analysis
p-value: <0.00195% CI: [-8.2, -3.6]Mixed Models Analysis
Secondary
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3
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.
Time frame: Baseline, Week 3
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Cariprazine (3-6 mg/Day) | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3 | -1.9 score on a scale | Standard Error 0.1 |
| Cariprazine (6-12 mg/Day) | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3 | -1.9 score on a scale | Standard Error 0.1 |
p-value: <0.00195% CI: [-0.9, -0.4]Mixed Models Analysis
p-value: <0.00195% CI: [-0.9, -0.3]Mixed Models Analysis