PMID- 24412468 OWN - NLM STAT- MEDLINE DCOM- 20140923 LR - 20220321 IS - 1573-2509 (Electronic) IS - 0920-9964 (Linking) VI - 152 IP - 2-3 DP - 2014 Feb TI - An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial. PG - 450-7 LID - S0920-9964(13)00658-0 [pii] LID - 10.1016/j.schres.2013.11.041 [doi] AB - INTRODUCTION: Cariprazine is an orally active and potent D3 and D2 partial agonist with preferential binding to D3 receptors in development for the treatment of schizophrenia and bipolar mania. This study (NCT00694707) evaluated the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia. METHODS: This study was a multinational, double-blind, randomized, placebo- and active-controlled, fixed-dose trial. Patients were randomized to receive placebo, cariprazine 1.5mg/d, cariprazine 3.0mg/d, cariprazine 4.5mg/d, or risperidone 4.0mg/d (for assay sensitivity) for 6 weeks of double-blind treatment and 2 weeks of safety follow-up. Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) total and Global Impressions-Severity of Illness (CGI-S) scores, respectively. Safety parameters included adverse events (AEs), vital signs, laboratory measures, and extrapyramidal symptom (EPS) scales. RESULTS: Of 732 randomized patients, 64% completed the study. PANSS total score improvement at Week 6 was statistically significant versus placebo for cariprazine 1.5mg/d, 3.0mg/d, and 4.5mg/d (least squares mean difference [LSMD]: -7.6, -8.8, -10.4, respectively; p<0.001; LOCF) and risperidone (-15.1, p<0.001; LOCF); significant improvement on CGI-S was demonstrated for all active treatments (p<0.05). The most frequent cariprazine AEs (>/= 5% and at least twice the rate of the placebo group) were insomnia, extrapyramidal disorder, akathisia, sedation, nausea, dizziness, and constipation. Mean changes in metabolic parameters were small and similar between groups. CONCLUSION: The results of this study support the efficacy and safety of cariprazine in patients with acute exacerbation of schizophrenia. CI - Copyright (c) 2013. Published by Elsevier B.V. FAU - Durgam, Suresh AU - Durgam S AD - Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: suresh.durgam@frx.com. FAU - Starace, Anju AU - Starace A AD - Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: anju.starace@frx.com. FAU - Li, Dayong AU - Li D AD - Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: dayong.li@frx.com. FAU - Migliore, Raffaele AU - Migliore R AD - Forest Research Institute, Harborside Financial Center, Plaza V, Jersey City, NJ, USA. Electronic address: raffaele.migliore@frx.com. FAU - Ruth, Adam AU - Ruth A AD - Prescott Medical Communications Group, 205 N. Michigan Ave, Suite 3400, Chicago, IL, USA. Electronic address: aruth@prescottmed.com. FAU - Nemeth, Gyorgy AU - Nemeth G AD - Gedeon Richter Plc, H-1103 Budapest 10, Gyomroi u. 19-21, Hungary. Electronic address: gy.nemeth@richter.hu. FAU - Laszlovszky, Istvan AU - Laszlovszky I AD - Gedeon Richter Plc, H-1103 Budapest 10, Gyomroi u. 19-21, Hungary. Electronic address: i.laszlovszky@richter.hu. LA - eng SI - ClinicalTrials.gov/NCT00694707 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140110 PL - Netherlands TA - Schizophr Res JT - Schizophrenia research JID - 8804207 RN - 0 (Antipsychotic Agents) RN - 0 (Piperazines) RN - F6RJL8B278 (cariprazine) SB - IM MH - Adolescent MH - Adult MH - Antipsychotic Agents/*therapeutic use MH - Basal Ganglia Diseases/chemically induced MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Piperazines/*therapeutic use MH - Psychiatric Status Rating Scales MH - Schizophrenia/*drug therapy MH - Time Factors MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Antipsychotic OT - Cariprazine OT - D(3) OT - Dopamine OT - Schizophrenia EDAT- 2014/01/15 06:00 MHDA- 2014/09/24 06:00 CRDT- 2014/01/14 06:00 PHST- 2013/08/27 00:00 [received] PHST- 2013/11/21 00:00 [revised] PHST- 2013/11/26 00:00 [accepted] PHST- 2014/01/14 06:00 [entrez] PHST- 2014/01/15 06:00 [pubmed] PHST- 2014/09/24 06:00 [medline] AID - S0920-9964(13)00658-0 [pii] AID - 10.1016/j.schres.2013.11.041 [doi] PST - ppublish SO - Schizophr Res. 2014 Feb;152(2-3):450-7. doi: 10.1016/j.schres.2013.11.041. Epub 2014 Jan 10.