Clinical Trials

Date: 2014-03-21

Type of information: Results

phase: 2b

Announcement: results

Company: Forest Laboratories (USA) Gedeon Richter (Hungary)

Product: cariprazine

Action mechanism:

dopamine D3 receptor partial agonist. Cariprazine has been discovered by researchers at Gedeon Richter. This orally active, potent dopamine D3-preferring D3/D2 receptor partial agonist is an atypical antipsychotic for the treatment of patients with schizophrenia and for patients with manic or mixed episodes associated with bipolar I disorder. The safety and efficacy of cariprazine was studied in a clinical trial program of more than 2700 patients. In addition, cariprazine is being investigated for the treatment of bipolar depression and adjunctive MDD in adults. Cariprazine is licensed to Actavis, now Allergan, in the U.S. and Canada.
Cariprazine is protected by a composition-of-matter patent that expires in 2027 without patent term extension.

Disease: major depressive disorder (MDD)

Therapeutic area: CNS diseases - Mental diseases

Country:

Trial details:

This international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose, 8-week Phase IIb study evaluated the efficacy, safety, and tolerability of cariprazine as adjunctive treatment in adult patients with MDD who demonstrated an inadequate response to ADT. Eligible patients were those who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for MDD, had a minimum score of 22 on the MADRS scale, and had an ongoing inadequate response to ADT.
Following a 7-14 day screening and washout period, a total of 819 patients between 18 and 65 years of age were randomized to one of three treatment groups (either cariprazine 1.0 – 2.0 mg/day + ADT, cariprazine 2.0 – 4.5 mg/day + ADT, or placebo + ADT) followed by a 1-week safety follow-up period. The primary endpoint was defined as change from baseline to end of week 8 in the MADRS total score. Statistically significant improvement in the MADRS total score was observed in the cariprazine 2.0 – 4.5 mg/day + ADT group relative to the placebo + ADT treatment group (cariprazine 2.0 – 4.5 mg/day + ADT: -2.2, p=0.0114 and cariprazine 1.0 – 2.0 mg/day + ADT: -0.9, p=0.2404) by MMRM analysis.Across both cariprazine dose groups the most common adverse events (incidence ?10% and greater than placebo) were akathisia, nausea, insomnia, somnolence, and fatigue.

Latest news:

• On March 21, 2014, Forest Laboratories and Gedeon Richter have announced positive topline results from a Phase IIb trial evaluating the efficacy and safety of cariprazine as adjunctive treatment in adult patients with Major Depressive Disorder (MDD) who have demonstrated an inadequate response to antidepressant therapy (ADT). The trial consisted of three treatment groups, cariprazine 1.0 – 2.0 mg/day + ADT and cariprazine 2.0 – 4.5 mg/day + ADT, and placebo + ADT. The group who received cariprazine 2.0 – 4.5 mg/day + ADT demonstrated statistically significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) total score versus placebo at 8 weeks, the primary endpoint.
Cariprazine is being developed for the treatment of schizophrenia and bipolar mania in adults. On November 21, 2013 the companies announced that the FDA issued a complete response letter regarding the new drug application for schizophrenia and bipolar mania. In addition, there are ongoing investigational clinical trials for the treatment of bipolar depression and as adjunctive treatment of major depressive disorder in adults.