Forest Laboratories and Gedeon Richter have reported preliminary top-line results from a Phase III clinical trial of Cariprazine (RGH-188), an investigational anti-psychotic agent, used to treat patients with acute mania associated with bipolar I disorder.
Discovered by researchers at Gedeon Richter, Cariprazine is an orally active, potent dopamine D3-preferring D3/D2 receptor partial agonist, which is currently being investigated in clinical studies for patients with schizophrenia, bipolar depression, and as an adjunct treatment for major depressive disorder.
The Phase III multicentre double-blind placebo-controlled parallel-group study is designed to examine the efficacy, safety and tolerability of Cariprazine monotherapy in patients with acute mania associated with bipolar I disorder.
During the five-week study, 497 men and women aged 18-65 years were randomised into three treatment groups and received at least one dose of either Cariprazine 3-6mg/day, Cariprazine 6-12 mg/day or placebo.
The Young Mania Rating Scale (YMRS) is a comprehensive, clinician-rated instrument used to evaluate the severity of mania in bipolar patients, including parameters such as elevated mood, increased motor activity-energy, sleep and irritability.
In the study, 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.
The trial demonstrated that patients treated with Cariprazine experienced considerable improvements in symptoms compared to placebo-treated patients observed as early as day five of treatment and at each subsequent time point studied.
The study also showed that overall premature discontinuation rates were 23% for Cariprazine 3-6mg/day, 30% for Cariprazine 6-12mg/day, and 24% for placebo.
Marco Taglietti, MD, senior vice president of research and development and president, Forest Research Institute, said: "These positive phase III results further demonstrate the opportunity for cariprazine as a potential new treatment option for patients suffering from bipolar mania."
Gedeon Richter research director Zsolt Szombathelyi said: "In the three consecutive positive trials, statistically significant results demonstrated improvement in symptoms compared to placebo, importantly including the low dose range arm."