Abstract
This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P <0.001) and Clinical Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P <0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 367-373 |
| Number of pages | 7 |
| Journal | Journal of Clinical Psychopharmacology |
| Volume | 35 |
| Issue number | 4 |
| DOIs | |
| State | Published - Aug 11 2015 |
| Externally published | Yes |
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Keywords
- antipsychotic
- cariprazine
- dopamine
- dopamine D<inf>3</inf>
- receptors
- schizophrenia
ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology (medical)
Cite this
Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia : Results from an International, Phase III Clinical Trial. / Kane, John M.; Zukin, Stephen; Wang, Yao; Lu, Kaifeng; Ruth, Adam; Nagy, Krisztián; Laszlovszky, István; Durgam, Suresh.
In: Journal of Clinical Psychopharmacology, Vol. 35, No. 4, 11.08.2015, p. 367-373.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia
T2 - Results from an International, Phase III Clinical Trial
AU - Kane, John M.
AU - Zukin, Stephen
AU - Wang, Yao
AU - Lu, Kaifeng
AU - Ruth, Adam
AU - Nagy, Krisztián
AU - Laszlovszky, István
AU - Durgam, Suresh
PY - 2015/8/11
Y1 - 2015/8/11
N2 - This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P <0.001) and Clinical Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P <0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia.
AB - This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P <0.001) and Clinical Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P <0.001). Common treatment-emergent adverse events (≥5% and twice the rate of placebo) in both cariprazine groups were akathisia, extrapyramidal disorder, and tremor; most were mild to moderate in severity. Mean changes in metabolic parameters were generally small and similar between groups. Prolactin levels decreased in all groups. In conclusion, cariprazine 3 to 6 and 6 to 9 mg/d versus placebo demonstrated significant improvement on primary and secondary efficacy parameters. Cariprazine was generally well tolerated. These results suggest that cariprazine may be a new and effective treatment for schizophrenia.
KW - antipsychotic
KW - cariprazine
KW - dopamine
KW - dopamine D<inf>3</inf>
KW - receptors
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84936931469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84936931469&partnerID=8YFLogxK
U2 - 10.1097/JCP.0000000000000346
DO - 10.1097/JCP.0000000000000346
M3 - Article
C2 - 26075487
AN - SCOPUS:84936931469
VL - 35
SP - 367
EP - 373
JO - Journal of Clinical Psychopharmacology
JF - Journal of Clinical Psychopharmacology
SN - 0271-0749
IS - 4
ER -