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

Abstract

Background: 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: atypical antipsychotic; cariprazine; post hoc analysis; safety and tolerability; schizophrenia.

Conflict of interest statement

Ágota Barabássy, Barbara Sebe, Károly Acsai, István Laszlovszky, Balázs Szatmári and György Németh are employees of Gedeon Richter Plc. Barbara Sebe and Károly Acsai report personal fees from Gedeon Richter Plc., outside the submitted work. István Laszlovszky reports personal fees from Gedeon Richter Plc., during the conduct of the study; in addition, István Laszlovszky has a patent cariprazine issued. Balázs Szatmári reports personal fees from Gedeon Richter Plc., outside the submitted work; in addition, Balázs Szatmári has a patent cariprazine issued. Willie R. Earley reports being an employee of AbbVie, and share- or stock-holder of AbbVie, AstraZeneca and Eli Lilly; being a former employee of Allergan and Forest LP during the conduct of the study and outside the submitted work; and being previously employed with Forest LP, AstraZeneca, and Eli Lilly outside the submitted work. György Németh reports personal fees from Gedeon Richter Plc., outside the submitted work; in addition, Dr György Németh has a patent cariprazine issued. The authors report no other potential conflicts of interest for this work.

© 2021 Barabássy et al.