Manic Disorders

May 25, 2015

Sunovion Pharmaceuticals issued results of Latuda (lurasidone HCl) related to adults with major depressive disorder (MDD) who presented with a limited number of associated manic symptoms (mixed features). In a randomized, double- blind, placebo-controlled, six-week clinical trial, patients were randomized to receive six weeks of treatment with flexibly-dosed Latuda 20 – 60mg/day (N=109) or placebo (N=102). The primary efficacy endpoint in the study was change from baseline at week six in Montgomery- Asberg Depression Rating Scale (MADRS) total score. The key secondary endpoint was change from baseline at week six in the Clinical Global Impression, Severity (CGI-S) score, which assessed global severity of illness. Results from the study showed treatment with Latuda was associated with a statistically significant reduction in MADRS total scores at the end of the study (week six) compared with placebo (-0.5 v. -13; p<0.0001; Cohen’s d effect size=0.80), with separation from placebo starting at the first post-baseline assessment (week one). In addition, patients treated with Latuda experienced a statistically significant reduction in change from baseline at week six in CGI-S scores compared with placebo (-1.83 v. -1.18; p<0.0001; Cohen’s d effect size=0.60), with separation from placebo starting at week two, as well as significant differences from placebo on all other secondary efficacy endpoints, including manic symptoms. Latuda was generally well- tolerated with low rates of change in weight and metabolic parameters and an overall discontinuation rate lower than placebo (6.4% v. 14.7%). The most common adverse events reported with an incidence =5% and greater than placebo in patients receiving Latuda were nausea (6.4% v. 2%) and somnolence (5.5% v. 1%).

February 13, 2012

Forest Laboratories and Gedeon Richter reported results from a phase III trial of cariprazine for the treatment of acute mania associated with bipolar 1 disorder. This multicenter, double-blind, placebo-controlled, parallel-group study enrolled 497 subjects who were randomized to receive at least one dose of cariprazine 3-6mg/day, 6-12 mg/day or placebo for up to three weeks. The primary protocol-specified endpoint was change from baseline to week three on the Young Mania Rating Scale. Statistically significant improvement was noted in both cariprazine dose groups (3-6mg/day: -6.1 points, p<0.001 and 6-12 mg/day: -5.9 points, p<0.001) compared to the placebo group. These improvements were observed as early as day five of treatment and at each subsequent time point studied. Cariprazine was generally well tolerated. The most common adverse events were akathisia (both cariprazine groups) and constipation (cariprazine 6-12 mg/day).

October 10, 2011

Forest Labs and Gedeon Richter released results from a phase III trial of cariprazine for acute mania associated with bipolar I disorder. This double-blind, placebo- controlled, parallel-group study enrolled 312 subjects who received at least one dose of either cariprazine 3-12mg or placebo daily for three weeks. The primary endpoint was change from baseline to week three on the Young Mania Rating Scale. Statistically significant improvement was observed in subjects receiving cariprazine versus placebo (-19.6 versus -15.3 placebo, respectively, p<0.001). Cariprazine was generally well tolerated with discontinuations due to adverse events similar between the treatment arms.

March 12, 2007

Memory Pharmaceuticals reported negative results from a phase IIa trial of MEM1003 for the treatment of acute mania in bipolar disorder. This double-blind, randomized, placebo-controlled trial enrolled 84 subjects who received MEM 1003 or placebo for 21 days, followed by an optional open-label four week treatment period. Drug administration was dosed at 60 mg twice a day, with up to two dose escalations, from 60 to 120 mg twice a day on the second day of treatment and from 120 to 180 mg twice a day on the third day of treatment. MEM1003 was well tolerated up to the highest dose. However none of the trial endpoints were met. These included the primary endpoint of at least 50% improvement from baseline in the Young Mania Rating Scale (YMRS) at 21 days and secondary endpoints of mean change from baseline in the YMRS, the Modified Clinical Global Impression - Bipolar Scale and the Montgomery-Asberg Depression Rating Scale at 21 days. Memory plans to further analyze the data in order to determine a future course of action for MEM1003 for this indication.

September 23, 2002

Seroquel, an investigational drug for acute mania, showed favorable results in a phase III randomized, double-blinded, placebo controlled study. The 3-week trial consisted of 91 subjects diagnosed with Bipolar I disorder and experiencing a manic episode. Each subject was randomly assigned a mean of 500 mg of Seroquel or placebo while mood stabilizers such as lithium or divalproex were administered unblinded prior to randomization. The results indicated that 54% of subjects treated with Seroquel demonstrated a significantly greater response rate compared to 32.6% of the placebo group. Additionally, 45.7% of subjects treated with Seroquel experienced a full resolution of their manic symptoms compared to the 25.8% of the placebo group on the Young Mania Rating Scale (YMRS). Seroquel is a product of AstraZeneca.

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