A Phase 3 interventional study of Cariprazine and Placebo in Mania and Bipolar I Disorder, sponsored by Forest Laboratories. Completed at 66 sites in 6 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-04-12.
Sponsored by Forest Laboratories · Phase 3, Interventional, and Treatment
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.
Exclusion Criteria:
Cariprazine 3 milligrams (mg) - 6 mg capsules oral administration, once per day for 3 weeks.
Drug: Cariprazine
Cariprazine 6 mg - 12 mg capsules oral administration, once per day for 3 weeks.
Drug: Cariprazine
Placebo dose-matching cariprazine capsules oral administration, once per day for 3 weeks.
Drug: Placebo
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.
Patients who meet eligibility criteria will be administered a once daily oral dose of placebo for three weeks.
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
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
| Milestone | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) |
|---|---|---|---|
| Started | 161 | 167 | 169 |
| Completed | 122 | 129 | 119 |
| Not completed | 39 | 38 | 50 |
| Withdrew: Adverse event | 8 | 15 | 25 |
| Withdrew: Insufficient therapeutic response | 15 | 2 | 5 |
| Withdrew: Protocol violation | 1 | 1 | 2 |
| Withdrew: Withdrawal of consent | 14 | 18 | 17 |
| Withdrew: Lost to follow-up | 0 | 1 | 1 |
| Withdrew: Other unspecified | 1 | 1 | 0 |
| Milestone | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) |
|---|---|---|---|
| Started | 144 | 146 | 148 |
| Completed | 139 | 146 | 141 |
| Not completed | 5 | 0 | 7 |
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.
| score on a scale | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) |
|---|---|---|---|
| Change From Baseline in the Young Mania Rating Scale (YMRS) Total Score at Week 3 | -12.5 ± 0.8 | -18.6 ± 0.8 | -18.5 ± 0.8 |
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.
| score on a scale | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) |
|---|---|---|---|
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total Score at Week 3 | -1.3 ± 0.1 | -1.9 ± 0.1 | -1.9 ± 0.1 |
Collected over First dose of study drug to 30 days past last dose (Up to 51 days). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 5/161 (3.1%) | 63/161 (39.1%) |
| Cariprazine (3-6 mg/Day) | — | 9/167 (5.4%) | 89/167 (53.3%) |
| Cariprazine (6-12 mg/Day) | — | 5/169 (3%) | 90/169 (53.3%) |
| Event | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) |
|---|---|---|---|
| ManiaPsychiatric disorders | 3/161 | 3/167 | 3/169 |
| Bipolar disorderPsychiatric disorders | 1/161 | 1/167 | 0/169 |
| Bipolar I disorderPsychiatric disorders | 1/161 | 1/167 | 1/169 |
| AggressionPsychiatric disorders | 0/161 | 1/167 | 0/169 |
| Endometrial cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/161 | 1/167 | 0/169 |
| HospitalisationSurgical and medical procedures | 0/161 | 1/167 | 0/169 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 0/161 | 1/167 | 0/169 |
| DepressionPsychiatric disorders | 0/161 | 0/167 | 1/169 |
| Event | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) |
|---|---|---|---|
| AkathisiaNervous system disorders | 8/161 | 29/167 | 38/169 |
| HeadacheNervous system disorders | 15/161 | 19/167 | 20/169 |
| NauseaGastrointestinal disorders | 9/161 | 16/167 | 19/169 |
| ConstipationGastrointestinal disorders | 5/161 | 8/167 | 18/169 |
| InsomniaPsychiatric disorders | 15/161 | 16/167 | 17/169 |
| Extrapyramidal disorderNervous system disorders | 8/161 | 16/167 | 12/169 |
| VomitingGastrointestinal disorders | 10/161 | 15/167 | 14/169 |
| RestlessnessPsychiatric disorders | 8/161 | 15/167 | 10/169 |
| DiarrhoeaGastrointestinal disorders | 12/161 | 4/167 | 9/169 |
| DyspepsiaGastrointestinal disorders | 5/161 | 7/167 | 10/169 |
Safety Population included all participants who received at least 1 dose of study drug.
| Age, Continuous(years) | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) | Total |
|---|---|---|---|---|
| Mean | 41.5 ± 11.4 | 43.1 ± 12.2 | 41.2 ± 11.3 | 41.9 ± 11.7 |
| Sex: Female, Male(Participants) | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) | Total |
|---|---|---|---|---|
| Female | 72 | 77 | 84 | 233 |
| Male | 89 | 90 | 85 | 264 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 10 | 10 | 4 | 24 |
| Not Hispanic or Latino | 151 | 157 | 165 | 473 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) | Total |
|---|---|---|---|---|
| White | 114 | 117 | 114 | 345 |
| Black/African American | 44 | 44 | 51 | 139 |
| Asian | 1 | 3 | 1 | 5 |
| American Indian or Alaska Native | 2 | 1 | 1 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 0 | 1 |
| Other | 0 | 1 | 1 | 2 |
| Weight(kilogram (kg)) | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) | Total |
|---|---|---|---|---|
| Mean | 81.70 ± 15.96 | 82.42 ± 16.22 | 81.49 ± 16.78 | 81.87 ± 16.30 |
| Height(centimeter (cm)) | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) | Total |
|---|---|---|---|---|
| Mean | 170.93 ± 9.88 | 170.99 ± 9.15 | 170.25 ± 9.36 | 170.72 ± 9.45 |
| Body Mass Index (BMI)(kg/meter(m)^2) | Placebo | Cariprazine (3-6 mg/Day) | Cariprazine (6-12 mg/Day) | Total |
|---|---|---|---|---|
| Mean | 27.99 ± 5.15 | 28.22 ± 5.29 | 28.04 ± 4.92 | 28.08 ± 5.12 |
This study is completed, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.
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Forest Laboratories