Clinical Trials

Date: 2014-03-31

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..

Disease: bipolar depression

Therapeutic area: CNS diseases

Country:

Trial details:

This international, randomized, placebo-controlled, fixed-dose, 8-week Phase IIb trial evaluated the efficacy and safety of cariprazine in the treatment of patients with depressive episodes of bipolar I disorder. Eligible patients included those with bipolar depression who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder with a current major depressive episode. Patients also had to have a minimum score of 20 on the 17-item Hamilton Depression Rating Scale (HAM-D), a minimum score of 2 on item 1 of the HAM-D, a minimum score of 4 on the CGI-S, and a maximum score of 10 on the Young Mania Rating Scale (YMRS) at both visit 1 and visit 2.
The study consisted of up to 14 days of screening followed by 8 weeks of double-blind treatment, followed by a 1-week safety follow-up period. During the double-blind treatment period, 584 patients 18 – 65 years of age were randomized to one of four treatment groups: cariprazine 0.75 mg/day, 1.5 mg/day, 3.0 mg/day, or placebo. The primary endpoint was change from baseline in the MADRS total score versus placebo at 6 weeks, using a mixed-effects model for repeated measures (MMRM) analysis.

Latest news:

• On March 31, 2014, Forest Laboratories and Gedeon Richter have announced positive topline results from a Phase IIb trial evaluating the efficacy and safety of the investigational antipsychotic cariprazine in patients with bipolar depression. The trial consisted of four treatment groups: cariprazine 0.75 mg/day, 1.5 mg/day, 3.0 mg/day, and placebo. Statistically significant improvements were observed in the cariprazine 1.5 mg/day group relative to placebo at 6 weeks for the primary endpoint, the Montgomery-Asberg Depression Rating Scale (MADRS) total score and the key secondary endpoint, the Clinical Global Impressions – Severity (CGI-S) score. The group who received cariprazine 1.5 mg/day demonstrated statistically significant improvement in the MADRS total score versus placebo at week 6 (cariprazine 0.75 mg/day: -1.9, p=0.1292; cariprazine 1.5 mg/day: -4.0, p=0.0030; cariprazine 3.0 mg/day: -2.5, p=0.1122). The key secondary endpoint was change from baseline in CGI-S total score versus placebo at 6 weeks, using an MMRM analysis. The group who received cariprazine 1.5 mg/day demonstrated statistically significant improvement in the CGI-S score versus placebo (cariprazine 0.75 mg/day: -0.1, p=0.3025; cariprazine 1.5 mg/day: -0.4, p=0.0132; cariprazine 3.0 mg/day: -0.3, p=0.1122).
Across all cariprazine doses, the most common adverse events were akathisia and insomnia.