Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results from an International, Phase III Clinical Trial

John M. Kane, Stephen Zukin, Yao Wang, Kaifeng Lu, Adam Ruth, Krisztián Nagy, István Laszlovszky, Suresh Durgam

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)367-373
Number of pages7
JournalJournal of Clinical Psychopharmacology
Volume35
Issue number4
DOIs
StatePublished - Aug 11 2015
Externally publishedYes

Fingerprint

Phase III Clinical Trials
Schizophrenia
Safety
Placebos
cariprazine
Basal Ganglia Diseases
Dopamine D3 Receptors
Psychomotor Agitation
Dopamine D2 Receptors
Vital Signs
Tremor
Therapeutics
Least-Squares Analysis
Prolactin
Suicide
Electrocardiography

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 journalArticle

Kane, John M. ; Zukin, Stephen ; Wang, Yao ; Lu, Kaifeng ; Ruth, Adam ; Nagy, Krisztián ; Laszlovszky, István ; Durgam, Suresh. / Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia : Results from an International, Phase III Clinical Trial. In: Journal of Clinical Psychopharmacology. 2015 ; Vol. 35, No. 4. pp. 367-373.
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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.",
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