PMID- 28836957 OWN - NLM STAT- MEDLINE DCOM- 20180321 LR - 20181202 IS - 1471-244X (Electronic) IS - 1471-244X (Linking) VI - 17 IP - 1 DP - 2017 Aug 24 TI - The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis. PG - 305 LID - 10.1186/s12888-017-1459-z [doi] LID - 305 AB - BACKGROUND: Schizophrenia is a chronic and debilitating neuropsychiatric disorder that often requires long-term pharmacotherapy to manage symptoms and prevent relapse. Cariprazine is a potent dopamine D(3) and D(2) receptor partial agonist that is FDA-approved in the US for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults; the recommended dose range is 1.5-6 mg/d. METHODS: To further characterize the long-term safety of cariprazine, data from two 48-week open-label, flexible-dose extension studies were pooled for post hoc analyses. Outcomes were evaluated in the pooled safety population (patients who received >/=1 dose of cariprazine during an open-label extension period); findings were summarized using descriptive statistics for the overall cariprazine group and in modal daily dose groups (1.5-3, 4.5-6, and 9 mg/d). RESULTS: Of the 679 patients in the overall cariprazine safety population, 40.1% completed the study. The only adverse events (AEs) leading to discontinuation of >/=2% of patients in any dose group were akathisia, worsening of schizophrenia, and psychotic disorder. Treatment-emergent AEs (TEAEs) of akathisia, insomnia, weight increased, and headache were reported in >/=10% of the overall population. Mean prolactin levels decreased in all dose groups (overall, -15.4 ng/mL). Clinically insignificant changes in aminotransferase levels and alkaline phosphatase were observed; no dose-response relationship was observed across groups. Mean total (-5.3 mg/dL), low-density lipoprotein (-3.5 mg/dL), and high-density lipoprotein (-0.8 mg/dL) cholesterol levels decreased; no dose-response relationship was observed for metabolic parameters. Mean change in body weight was 1.58 kg; body weight increase and decrease >/=7% occurred in 27% and 11% of patients, respectively. Mean changes in cardiovascular parameters, including blood pressure and pulse, were generally not considered clinically significant. EPS-related TEAEs that occurred in >/=5% of patients were akathisia, tremor, restlessness, and extrapyramidal disorder. CONCLUSION: In these post hoc pooled analyses of data from 2 long-term open-label studies, treatment with cariprazine was generally safe and well tolerated. Results support the safety and tolerability of cariprazine within the FDA-recommended dose range of 1.5-6 mg/d for schizophrenia. CLINICAL TRIALS REGISTRATION: NCT01104792, NCT00839852. FAU - Nasrallah, Henry A AU - Nasrallah HA AD - Saint Louis University, 1438 South Grand Blvd., Suite 105, St. Louis, MO, 63104, USA. hnasral@slu.edu. FAU - Earley, Willie AU - Earley W AD - Allergan, Harborside 5, 185 Hudson Street, Jersey City, NJ, 07311, USA. FAU - Cutler, Andrew J AU - Cutler AJ AD - Meridien Research, Inc., 8043 Cooper Creek Boulevard #107, Bradenton, FL, 34201, USA. FAU - Wang, Yao AU - Wang Y AD - Allergan, Harborside 5, 185 Hudson Street, Jersey City, NJ, 07311, USA. FAU - Lu, Kaifeng AU - Lu K AD - Allergan, Harborside 5, 185 Hudson Street, Jersey City, NJ, 07311, USA. FAU - Laszlovszky, Istvan AU - Laszlovszky I AD - Gedeon Richter, Plc, Gyomroi u. 32, Budapest, H-1103, Hungary. FAU - Nemeth, Gyorgy AU - Nemeth G AD - Gedeon Richter, Plc, Gyomroi u. 32, Budapest, H-1103, Hungary. FAU - Durgam, Suresh AU - Durgam S AD - Allergan, Harborside 5, 185 Hudson Street, Jersey City, NJ, 07311, USA. LA - eng SI - ClinicalTrials.gov/NCT01104792 SI - ClinicalTrials.gov/NCT00839852 PT - Journal Article DEP - 20170824 PL - England TA - BMC Psychiatry JT - BMC psychiatry JID - 100968559 RN - 0 (Antipsychotic Agents) RN - 0 (Piperazines) RN - F6RJL8B278 (cariprazine) SB - IM MH - Adult MH - Akathisia, Drug-Induced MH - Antipsychotic Agents/adverse effects/*therapeutic use MH - Female MH - Humans MH - Male MH - Piperazines/adverse effects/*therapeutic use MH - Randomized Controlled Trials as Topic MH - Schizophrenia/*drug therapy MH - Treatment Outcome PMC - PMC5571492 OTO - NOTNLM OT - Atypical antipsychotic OT - Cariprazine OT - Long-term safety OT - Open-label OT - Post hoc analysis OT - Schizophrenia COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The constituent clinical studies were conducted in full compliance with Food and Drug Administration guidelines for good clinical practice and in accordance with the ethical principles that have their origins in the Declaration of Helsinki. The protocol of each study was approved by an institutional review board at sites in the United States or independent ethics committee at sites outside of the United States (Additional file 1). The studies were conducted in compliance with guidelines for good clinical practice; all patients gave informed written consent to participate. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: HN has been a consultant for Acadia, Alkermes, Allergan, Boehringer Ingelheim, Grunenthal USA, Inc., Janssen Pharmaceuticals, Inc., Lundbeck, Merck Sharp & Dohme Corp., Novartis Corporation, Otsuka Pharmaceutical Co., Ltd., Roche/Genentech, Sunovion Pharmaceuticals, Inc., and Vanda Pharmaceuticals; he has served on speakers' bureaus for Acadia, Alkermes, Allergan, Janssen Pharmaceuticals, Inc., Otsuka Pharmaceuticals, Sunovion Pharmaceuticals, Inc. and Vanda; he has received grant/research support from Forest Pharmaceuticals, Inc., Otsuka Pharmaceutical Co., Ltd., and Roche/Genentech. AC has received research grants and consultant/speaker fees from Acadia, Alkermes, Allergan, AstraZeneca, Braeburn Pharmaceuticals, Forum Pharmaceuticals, Janssen (Johnson & Johnson), Eli Lilly, Lundbeck, Neurocrine, Novartis, Otsuka, Reckitt Benckiser, Sunovion, Takeda, Teva, and Vanda. SD, WE, YW, and KL acknowledge a potential conflict of interest as employees of Allergan. IL and GN acknowledge a potential conflict of interest as employees of Gedeon Richter Plc. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/08/25 06:00 MHDA- 2018/03/22 06:00 PMCR- 2017/08/24 CRDT- 2017/08/25 06:00 PHST- 2017/03/13 00:00 [received] PHST- 2017/08/11 00:00 [accepted] PHST- 2017/08/25 06:00 [entrez] PHST- 2017/08/25 06:00 [pubmed] PHST- 2018/03/22 06:00 [medline] PHST- 2017/08/24 00:00 [pmc-release] AID - 10.1186/s12888-017-1459-z [pii] AID - 1459 [pii] AID - 10.1186/s12888-017-1459-z [doi] PST - epublish SO - BMC Psychiatry. 2017 Aug 24;17(1):305. doi: 10.1186/s12888-017-1459-z.