Forest Labs and Gedeon Richter reported positive topline data from a Phase III clinical study evaluating the antipsychotic candidate cariprazine (RGH-188) in patients with bipolar 1 disorder-associated acute mania. Results from the three-week study indicated that in comparison with patients treated using placebo, those receiving cariprazine monotherapy demonstrated significant improvement in symptoms, assessed using the Young Mania Rating Scale (YMRS) as early as the fourth day of treatment and continuing throughout the trial period.
Cariprazine was generally well tolerated, with discontinuation due to adverse events occurring in 10% of the cariprazine group, and 7% of the placebo group. The overall premature discontinuation rate (due to all causes) was 32% for the cariprazine-treated patients, and 31% for placebo-treated patients. The firms say the most common adverse events associated with cariprazine were akathisia, extrapyramidal disorder, tremor, dyspepsia, and vomiting.
Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor partial agonist, which shows only low potency at receptor sites associated with adverse events. Originally developed at Hungarian firm Gedeon Richter, the drug is also in development for the treatment for schizophrenia, bipolar depression, and as an adjunctive treatment for MDD. Forest projects filing an IND for cariprazine during 2012.
Gedeon Richter says the Phase III data validate the D3/D2 partial agonist approach developed by the firm’s scientists. “These data, together with those of the Phase II program, prove that cariprazine provides a clinically meaningful improvement with good tolerability in patients with acute mania associated with bipolar I disorder,” comments Zsolt Szombathelyi, M.D., research director.