REAGILA®
(cariprazine) is a dopamine D3 receptor-preferring D3/D2 partial agonist,1,2and delivers simultaneous efficacy on both the positive and negative symptoms of schizophrenia.3-6 On this website, you’ll find the Summary of Product Characteristics approved in the EU and other resources, like the clinical trials supporting the short- and long-term efficacy and safety profile of REAGILA®.
Introduction
REAGILA® (cariprazine) delivers simulatenous efficacy on both the positive and negative symptoms of schizophrenia,1,2,3,4 and prevents relapse in the long term5. REAGILA was tested in two different patient populations with schizophrenia:
SCHIZOPHRENIA
with exacerbation of symptoms: REAGILA® is an effective, broad-spectrum treatment for schizophrenia symptoms1-3 and relapse prevention5
Cariprazine was tested in three pivotal, multinational, randomised, double-blind, placebo-controlled trials in non-elderly adults (age 18-60, mean duration of disease 11.4 years, total N=1792) hospitalised for an acute exacerbation of schizophrenia1-3. Six weeks of treatment with cariprazine demonstrated statistically superior improvements in the primary (PANSS total score) and secondary (CGI-S) efficacy outcomes vs. placebo over its entire dose range studied. The onset of significant superiority vs. the placebo response in PANSS total scores was generally observed as early as week 2 for the lower cariprazine doses (1.5-3.0 mg/day) and already at week 1 for the higher doses (4.5 mg/day and above)1-3.To support the long-term efficacy of cariprazine, a multinational randomised-withdrawal relapse prevention study was conducted in patients (N=200) whose disease remained stable during a 20-week open-label cariprazine therapy. After randomisation to a double-blind treatment of up to 72-week duration, cariprazine 3-9 mg/day cut the risk of relapse by more than half vs. placebo. In the approved dose range of 3-6 mg/day, the risk of relapse was reduced by 60% (N=102, 95%CI: 18-80%).5
SCHIZOPHRENIA
with predominant negative symptoms: REAGILA® is the only antipsychotic with a proven superiority over another second- generation antipsychotic4
Negative symptoms are a key feature of schizophrenia that pose a strong limitation on the real-life functioning of patients. In order to establish whether antipsychotic drugs are truly effective on primary negative symptoms (as opposed to negative symptoms secondary to positive, extrapyramidal or depressive symptoms), studies in specific populations are required6.A multinational, randomised, double-blind, active-controlled trial was conducted with a 26-week treatment duration in 460 adults (18-65) with schizophrenia eliciting predominant negative symptoms.4 Cariprazine (4.5 mg/day) was shown to be superior to risperidone (4.0 mg/day) in reducing the negative symptoms (PANSS FSNS, P=0.0022) and improving patients functionality and personal relationships (PSP total score, P<0.0001). Cariprazine’s effect size on negative symptoms vs. risperidone (0.31) was comparable to the effect size of other antipsychotics vs. placebo (0.42) in this patient population, thus almost doubling the total effect size vs. placebo (although this is an indirect comparison). These improvements purely occurred due to the improvement of negative symptoms independently of those in positive, depressive, or extrapyramidal symptoms.4
In open-label extension studies for up to 48 weeks of cariprazine therapy (N=679)7,8, the results from 350 patient-years of exposure support the god safety and tolerability profile of cariprazine within the dose range of 1.5–6 mg/day approved by both the FDA and EMA for the treatment of schizophrenia. 9
The D2/D3 receptor partial agonist cariprazine’s broad-spectrum efficacy, good tolerability, and advantage on primary negative symptoms vs. risperidone is attributed to its in vitro as well as in vivo preference for D3 receptors, a unique feature among antipsychotics, and the considerable affinity to 5-HT1A receptors.10,11
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References for website description
- Stahl SM. Mechanism of action of cariprazine. CNS Spectrums 2016;21:123-27.
- Citrome L. Cariprazine for the treatment of schizophrenia: a review of this dopamine D3-preferring D3/D2 receptor partial agonist. Clin Schizophr Relat Psychoses. 2016 Summer;10(2):109-19.
- Durgam S, Starace A, Li D, Migliore R, Ruth A, Németh G, Laszlovszky I. An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial. Schizophr Res. 2014;152(2–3):450–457. https://www.ncbi.nlm.nih.gov/pubmed/24412468
- Durgam S, Cutler AJ, Lu K, Migliore R, Ruth A, Laszlovszky I, Németh G, Meltzer HY. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial. J Clin Psychiatry. 2015 Dec; 76(12):e1574-1582. https://www.ncbi.nlm.nih.gov/pubmed/26717533
- Kane JM, Zukin S, Wang Y, Lu K, Ruth A, Nagy K, Laszlovszky I, Durgam S. Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial. J Clin Psychopharmacol. 2015 Aug; 35(4):367-373. https://www.ncbi.nlm.nih.gov/pubmed/26075487
- Németh G, Laszlovszky I, Czobor P, Szalai E, Szatmári B, Harsányi J, Barabássy Á, Debelle M, Durgam S, Bitter I, Marder S, Fleischhacker WW. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial. Lancet 2017;389:1103-13.
References for Introduction
2 Durgam S, Cutler AJ, Lu K, Migliore R, Ruth A, Laszlovszky I, Németh G, Meltzer HY. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial. J Clin Psychiatry. 2015 Dec; 76(12):e1574-1582. https://www.ncbi.nlm.nih.gov/pubmed/26717533
3 Kane JM, Zukin S, Wang Y, Lu K, Ruth A, Nagy K, Laszlovszky I, Durgam S. Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial. J Clin Psychopharmacol. 2015 Aug; 35(4):367-373. https://www.ncbi.nlm.nih.gov/pubmed/26075487
4 Németh G, Laszlovszky I, Czobor P, Szalai E, Szatmári B, Harsányi J, Barabássy Á, Debelle M, Durgam S, Bitter I, Marder S, Fleischhacker WW. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial. Lancet 2017;389:1103-13.
https://www.ncbi.nlm.nih.gov/pubmed/28185672
5 Durgam S, Earley W, Li R, Li D, Lu K, Laszlovszky I, Fleischhacker WW, Nasrallah HA. Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial. Schizophr Res. 2016;176(2-3):264-271. https://www.ncbi.nlm.nih.gov/pubmed/27427558 (Corrigendum: Schizophr Res. 2018;192:493.)
6 Krause M, Zhu Y, Huhn M, Schneider-Thoma J, Bighelli I, Nikolakopoulou A, Leucht S. Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: a systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2018 Oct;268(7):625-639.
7 Durgam S, Greenberg WM, Li D, Lu K, Laszlovszky I, Nemeth G, Migliore R, Volk S4 Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study. Psychopharmacology. 2017;234(2):199–209. https://www.ncbi.nlm.nih.gov/pubmed/27807604
8 Cutler AJ, Durgam S, Wang Y, Migliore R, Lu K, Laszlovszky I, Németh G. Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study. CNS Spectr. 2018;23:39–50. https://www.ncbi.nlm.nih.gov/pubmed/28478771
9 Nasrallah HA, Earley W, Cutler AJ, Wang Y, Lu K, Laszlovszky I, Németh G, Durgam S. The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis. BMC Psychiatry 2017; 17:305 DOI 10.1186/s12888-017-1459-z. https://www.ncbi.nlm.nih.gov/pubmed/28836957
