Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies

Ágota Barabássy,1 Barbara Sebe,1 Károly Acsai,1 István Laszlovszky,1 Balázs Szatmári,1 Willie R Earley,2 György Németh1 1Medical Division, Gedeon Richter Plc, Budapest, Hungary; 2Clinical Development, AbbVie, Madis...

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Autores principales:	Barabássy Á, Sebe B, Acsai K, Laszlovszky I, Szatmári B, Earley WR, Németh G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	cariprazine atypical antipsychotic schizophrenia safety and tolerability post hoc analysis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/f3d8aa158a174751acf576f4c6006005
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spelling	oai:doaj.org-article:f3d8aa158a174751acf576f4c60060052021-12-02T14:26:38ZSafety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies1178-2021https://doaj.org/article/f3d8aa158a174751acf576f4c60060052021-04-01T00:00:00Zhttps://www.dovepress.com/safety-and-tolerability-of-cariprazine-in-patients-with-schizophrenia--peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Ágota Barabássy,1 Barbara Sebe,1 Károly Acsai,1 István Laszlovszky,1 Balázs Szatmári,1 Willie R Earley,2 György Németh1 1Medical Division, Gedeon Richter Plc, Budapest, Hungary; 2Clinical Development, AbbVie, Madison, NJ, USACorrespondence: Ágota BarabássyMedical Division, Gedeon Richter Plc, Gyömrői út 19– 21, Budapest, 1103, HungaryTel +36 1 505 7017Fax +36 1 261 5815Email barabassya@richter.huBackground: Long-term treatment with antipsychotic agents is indicated for patients with schizophrenia, but treatment is associated with adverse events (AEs) that contribute to medication discontinuation and nonadherence. Understanding drug safety profiles is critical to avoid unwanted side effects. Cariprazine is a potent dopamine D3/D2 receptor partial agonist that is approved for the treatment of adults with schizophrenia (EU, US) and acute manic/mixed and depressive episodes associated with bipolar I disorder (US).Methods: Post hoc analyses were conducted to characterize the safety profile of cariprazine within the recommended 1.5– 6 mg/d dose range for schizophrenia; data from 8 short- or long-term clinical trials were analyzed.Results: In the pooled cariprazine-treated safety population (n=2048), the rate of study completion was 52.8%, with withdrawal of consent, insufficient response, and AEs the most common reasons for premature discontinuation. The most commonly reported AEs (> 10%) in the overall cariprazine-treatment group were akathisia (14.6%), insomnia (14.0%), and headache (12.1%); most AEs were considered mild (71.0%) or moderate (26.5%). Most akathisia was mild/moderate (97.5%) and > 93% of patients remained on treatment; akathisia events were managed by rescue medications (56.3%) or dose reduction (18.3%). The metabolic profile of cariprazine was neutral in patients with short- and long-term exposure; mean weight gain was 1 kg for overall cariprazine, with an AE of weight increased reported for 5.1%. Other AEs of special interest that occurred at > 3% for overall cariprazine were extrapyramidal disorder (7.0%), sedation (3.7%), and somnolence (3.1%); prolactin elevation, cognition impairment, sexual dysfunction, suicidality, and QT prolongation occurred at ≤ 1%.Conclusion: Akathisia, the most common cariprazine-related AE, was mild/moderate and resulted in few study discontinuations; symptoms were well managed and most patients remained on treatment. Results of this analysis indicated that cariprazine in the recommended dose range was safe and generally well tolerated in patients with schizophrenia.Trial Registration: Studies registered with ClinicalTrials.gov (NCT00404573, NCT01104779, NCT00694707, NCT01104766, NCT01104792, NCT00839852, and NCT01412060) and EudraCT (2012– 005485-36).Keywords: cariprazine, atypical antipsychotic, schizophrenia, safety and tolerability, post hoc analysisBarabássy ÁSebe BAcsai KLaszlovszky ISzatmári BEarley WRNémeth GDove Medical Pressarticlecariprazineatypical antipsychoticschizophreniasafety and tolerabilitypost hoc analysisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 957-970 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cariprazine atypical antipsychotic schizophrenia safety and tolerability post hoc analysis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	cariprazine atypical antipsychotic schizophrenia safety and tolerability post hoc analysis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Barabássy Á Sebe B Acsai K Laszlovszky I Szatmári B Earley WR Németh G Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies
description	Ágota Barabássy,1 Barbara Sebe,1 Károly Acsai,1 István Laszlovszky,1 Balázs Szatmári,1 Willie R Earley,2 György Németh1 1Medical Division, Gedeon Richter Plc, Budapest, Hungary; 2Clinical Development, AbbVie, Madison, NJ, USACorrespondence: Ágota BarabássyMedical Division, Gedeon Richter Plc, Gyömrői út 19– 21, Budapest, 1103, HungaryTel +36 1 505 7017Fax +36 1 261 5815Email barabassya@richter.huBackground: Long-term treatment with antipsychotic agents is indicated for patients with schizophrenia, but treatment is associated with adverse events (AEs) that contribute to medication discontinuation and nonadherence. Understanding drug safety profiles is critical to avoid unwanted side effects. Cariprazine is a potent dopamine D3/D2 receptor partial agonist that is approved for the treatment of adults with schizophrenia (EU, US) and acute manic/mixed and depressive episodes associated with bipolar I disorder (US).Methods: Post hoc analyses were conducted to characterize the safety profile of cariprazine within the recommended 1.5– 6 mg/d dose range for schizophrenia; data from 8 short- or long-term clinical trials were analyzed.Results: In the pooled cariprazine-treated safety population (n=2048), the rate of study completion was 52.8%, with withdrawal of consent, insufficient response, and AEs the most common reasons for premature discontinuation. The most commonly reported AEs (> 10%) in the overall cariprazine-treatment group were akathisia (14.6%), insomnia (14.0%), and headache (12.1%); most AEs were considered mild (71.0%) or moderate (26.5%). Most akathisia was mild/moderate (97.5%) and > 93% of patients remained on treatment; akathisia events were managed by rescue medications (56.3%) or dose reduction (18.3%). The metabolic profile of cariprazine was neutral in patients with short- and long-term exposure; mean weight gain was 1 kg for overall cariprazine, with an AE of weight increased reported for 5.1%. Other AEs of special interest that occurred at > 3% for overall cariprazine were extrapyramidal disorder (7.0%), sedation (3.7%), and somnolence (3.1%); prolactin elevation, cognition impairment, sexual dysfunction, suicidality, and QT prolongation occurred at ≤ 1%.Conclusion: Akathisia, the most common cariprazine-related AE, was mild/moderate and resulted in few study discontinuations; symptoms were well managed and most patients remained on treatment. Results of this analysis indicated that cariprazine in the recommended dose range was safe and generally well tolerated in patients with schizophrenia.Trial Registration: Studies registered with ClinicalTrials.gov (NCT00404573, NCT01104779, NCT00694707, NCT01104766, NCT01104792, NCT00839852, and NCT01412060) and EudraCT (2012– 005485-36).Keywords: cariprazine, atypical antipsychotic, schizophrenia, safety and tolerability, post hoc analysis
format	article
author	Barabássy Á Sebe B Acsai K Laszlovszky I Szatmári B Earley WR Németh G
author_facet	Barabássy Á Sebe B Acsai K Laszlovszky I Szatmári B Earley WR Németh G
author_sort	Barabássy Á
title	Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies
title_short	Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies
title_full	Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies
title_fullStr	Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies
title_full_unstemmed	Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies
title_sort	safety and tolerability of cariprazine in patients with schizophrenia: a pooled analysis of eight phase ii/iii studies
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/f3d8aa158a174751acf576f4c6006005
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Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies

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