Forest Laboratories and Gedeon Richter have released preliminary top-line results from a phase III clinical trial of cariprazine (RGH-188), an investigational antipsychotic agent, in patients with acute mania associated with bipolar I disorder.

For the primary endpoint, the Young Mania Rating Scale (YMRS), the data showed cariprazine-treated patients with acute manic episodes experienced significant improvements in symptoms compared to placebo-treated patients observed as early as day five of treatment.

The results of this study were consistent with the results observed in two previously completed pivotal placebo-controlled cariprazine studies in the same patient population.

"In the three consecutive positive trials, statistically significant results demonstrated improvement in symptoms compared to placebo, importantly including the low dose range arm," said Zsolt Szombathelyi, M.D., research director of Gedeon Richter.

During the most recent five-week study, 497 men and women, 18-65 years of age and meeting the Diagnostic and Statistical Manual of Mental Disorders criteria for bipolar I disorder, were randomized into three treatment groups and received at least one dose of either cariprazine 3-6mg/day (n=167), cariprazine 6-12mg/day (n=169) or placebo (n=161). Following a wash-out screening period of four to seven days, patients received treatment for up to three weeks, followed by a two-week period of safety assessments. Patients were hospitalized throughout screening and for at least the first 14 days following initiation of treatment.

The primary protocol-specified endpoint was change from baseline to week three on the YMRS, using the mixed-effects model of repeated measures (MMRM) analyses. Statistically significant improvement was noted in both cariprazine dose groups (3-6mg/day: -6.1 points, p <0.001 and 6-12mg/day: -5.9 points, p < 0.001) relative to patients receiving placebo on the YMRS scale by MMRM analysis. Further analyses of the data will be completed in the coming weeks.

Cariprazine also is currently being investigated in clinical studies for patients with schizophrenia, bipolar depression and as an adjunct treatment for Major Depressive Disorder.