The U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application for cariprazine (Vraylar, Allergan) for the treatment of depressive episodes associated with bipolar I disorder in adults. Cariprazine is also approved to treat manic or mixed episodes associated with bipolar I disorder in adults. The new indication makes cariprazine the first and only dopamine and serotonin partial agonist to treat the full spectrum of bipolar I symptoms in manic, mixed, and depressive episodes.The efficacy of cariprazine in the treatment of bipolar I depression has been demonstrated in three positive pivotal trials, including RGH-MD-53, RGH-MD-54 and RGH-MD-56 and data from all three trials were included in the supplemental new drug application.
In the three studies, RGH-MD-53, RGH-MD-54 and RGH-MD-56, cariprazine demonstrated greater improvement than placebo for the change from baseline to week six on the Montgomery Asberg Depression Rating scale (MADRS) total score. In all three studies, the cariprazine 1.5 mg dose demonstrated statistical significance over placebo; additionally, in RGH-MD-54, the cariprazine 3.0 mg dose demonstrated statistical significance over placebo. Common adverse events reported in the pivotal trials were nausea, akathisia, restlessness, and extrapyramidal symptoms. In RGH-MD-53, researchers examined the efficacy, safety and tolerability of cariprazine. The investigators randomly allocated 493 adults with bipolar I depression 1:1:1 to receive treatment with placebo, cariprazine 1.5 mg or cariprazine 3.0 mg. Overall, cariprazine was well-tolerated. The study met the primary and secondary endpoints for the 1.5 mg dose group, demonstrating greater improvement in the MADRS total score (p = 0.0417) and the Clinical Global Impression Scale-Severity (CGI-S) score (p = 0.0417) than placebo from baseline to week 6. Although cariprazine 3.0 mg showed improvement over placebo, it was not significant.
>> Allergan Press Release
Here you may find the Clinical Trial Results from RGH-MD-56 and RGH-MD-54. The results for RHG-MD-53 have not been published yet. Data can be found in the April 3, 2018 Allegan Press Release.
Durgam S et al. Am J Psychiatry. 2016;173(3):271-81. Abstract
Earley W et al. Am J Psychiatry. 2019;Epub ahead of print. Abstract
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