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Lupus Clinical Trials

New Medical Therapies™

Bipolar Disorder

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.

September 6, 2010

Forest Labs and Gedeon Richter reported positive preliminary results from a phase II trial of cariprazine for the treatment of bipolar depression. This randomized double-blind, placebo-controlled, flexible-dose group study enrolled 233 adult subjects across multiple U.S. sites. Following a wash-out period the subjects received either 0.25 - 0.75 mg per day of cariprazine, 1.5 - 3.0 mg per day of cariprazine or placebo. The primary endpoint was defined as a change from baseline to Week 8 in the Montgomery Asberg Depression Rating Scale (MADRS) total score compared to placebo. While the overall difference observed between the cariprazine and placebo-treated groups was not statistically significant, over the course of the trial there was evidence of a clinically relevant treatment effect in the high-dose arm of the study compared to placebo. Cariprazine was well tolerated.

March 23, 2009

Cephalon issued positive results from a phase II trial of Nuvigil for the treatment of major depressive disorder in adults with bipolar I disorder. This 8-week, double-blind, placebo-controlled trial enrolled 257 adult subjects with bipolar I disorder, who experienced a major depressive episode that was not completely managed by their other treatment. The subjects received either placebo or armodafinil (150 mg) once a day in addition to mood stabilizers, for eight weeks. The primary endpoint was an improvement over placebo on the 30-Item Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C30) scale. The subjects who received taking Nuvigil as adjunctive therapy showed significant improvement of depressive symptoms over placebo (p≡0.042). Nuvigil was generally well tolerated.

December 15, 2008

Alexza reported positive results from the phase III trial of AZ-004 for the treatment of acute agitation in bipolar disorder. This randomized, double-blind, placebo-controlled study enrolled 314 acutely-agitated patients with bipolar I disorder, in the US. The subjects received AZ-004 at two dose levels, 5 mg and 10 mg and were eligible to receive up to three doses of AZ-004 in a 24-hour period. The primary endpoint was the change from baseline in the PANSS Excited Component score (PEC score), measured at two hours after the first dose. Both the 5 mg and the 10 mg dose of AZ-004 met the primary endpoint, showing a highly statistically significant improvement compared to placebo (p<0.0001). The key secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) score, measured at two hours after the first dose. Both the 10 mg and the 5 mg doses of AZ-004 showed highly statistically significant differences versus placebo (p<0.0001). AZ-004 exhibited a rapid onset of effect. At ten minutes post-dose, the first assessment following dosing, the 10 mg dose showed a highly statistically significant improvement in the PEC score compared to placebo (p<0.0001). This improvement was sustained at all measurement time points throughout the 24-hour study period, compared to placebo. In addition, the duration of the clinical benefit of AZ-004, as measured by the need for additional study drug and/or rescue medication by the 4-hour time point, was significantly different between the arms. In the placebo arm, 64% of the subjects required more than one dose of the study drug and/or rescue medication compared to 40% of the 5 mg group (p≡0.0019) and 25% of the 10 mg group (p<0.0001). AZ-004 was generally safe and well tolerated.

October 6, 2008

Forest Labs and Gedeon Richter released positive preliminary results from a phase II trial of cariprazine for the treatment of acute mania associated with bipolar 1 disorder. This double-blind, placebo-controlled, flexible-dose study enrolled 236 subjects who were randomized to receive at least one dose of cariprazine (3-12 mg per day) or placebo. The treatment period lasted three weeks. The primary endpoint was change from baseline to Week 3 on the Young Mania Rating Scale (YMRS). Statistically significant improvement was observed in subjects receiving all cariprazine doses compared to those receiving placebo in the last observation carried forward analysis (-15.0 cariprazine versus -8.9 placebo; p < 0.0001). Statistically significant improvement in the YMRS scale was also noted in the mixed model repeated measure analysis (-15.5 cariprazine versus -8.5 placebo; p < 0.0001) and the observed-cases analysis (-19.1 cariprazine versus -13.6 placebo; p < 0.0001).Treatment was well tolerated. With an adverse event profile similar to placebo. Based on the results the companies plan to move forward with the development of cariprazine.

November 19, 2007

Repligen released positive results from a phase II trial of RG2417 for the treatment of bipolar disorder. This multi-center study enrolled eighty-four subjects who received RG2417 or a placebo over a six-week period. The co-primary endpoints were an improvement on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression of Change in Bipolar Disorder scale (CGI-BP-C). The subjects were measured at baseline and then weekly over the trial duration. Over the six-week treatment period, RG2417 led to a statistically significant improvement in the symptoms of depression over placebo on the MADRS (p=0.03) and a strong trend toward improvement on the CGI-BP-C (p=0.06). Based on the results, Repligen plans to move forward with the development of RG2417.

May 28, 2007

Organon released positive results from a phase III trial of asenapine for the treatment of bipolar I disorder. This double-blind trial enrolled 488 subjects with a manic or a mixed episode of bipolar I disorder and a baseline Young Mania Rating Scale (YMRS) score greater than or equal to 20. Subjects were randomized to receive asenapine (5-10 mg twice daily; average daily dose, 18.2 mg), olanzapine (5-20 mg once daily; average daily dose, 15.8 mg), or placebo for three weeks. The primary endpoint was a reduction in YMRS total score at day 21. Statistical significance was reached for this endpoint in the active treatment groups, asenapine and olanzapine, versus placebo (-10.8 and -12.6, respectively, vs. -5.5; both p<0.0001). Treatment was well tolerated, with adverse events mild to moderate in nature. Based on the results Organon plans to move toward the approval of asenapine.

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.

May 30, 2005

New River Pharmaceuticals has announced positive results of a phase III trial of NRP104, their amino- acid-conjugated stimulant under investigation for the treatment of pediatric attention deficit hyperactivity disorder (ADHD). Trial data met both primary and secondary efficacy endpoints, with all trial doses producing significant improvements in symptom severity score on both the ADHD Rating Scale and the Conners' Parent Rating System, vs. placebo (p<0.0001). Overall safety and tolerability profiles were considered positive and predictable. This randomized double-blind, placebo-controlled study enrolled 285 pediatric ADHD patients ages 6-12 across 45 sites, who received one of three oral doses of NRP104 or placebo. The company announced that these results would serve to support NDA filing by the end of 2005.

Shire Pharmaceuticals has issued combined results of a pair of phase III trials of Equetro (carbamazepine ER), for the treatment of refractory bipolar I disorder at the Annual Meeting of the American Psychiatric Association. Equetro was approved for this indication in December 2004. The pooled data have indicated that the drug was efficacious in improving manic symptom severity score on the Young Mania Rating Scale (YMRS). Specifically, subjects refractory to valproate who received Equetro experienced a mean score reduction of 10.8 points, vs. 5.7 points for placebo (p=0.04); subjects refractory to lithium experienced a mean score reduction of 11.6 points on Equetro, vs. 4.0 points for placebo (p=0.03). The pooled analysis of these randomized double-blind, placebo-controlled studies considered data from 115 subjects.

June 9, 2003

Bristol Myers Squibb reported positive results from two late phase trials investigating aripiprazole, a previously approved schizophrenia drug for the new indication of bipolar disorder. A three-week, double blind, placebo-controlled trial enrolled 272 subjects with bipolar disorder experiencing an acute manic episode. Results showed subjects who received aripiprazole showed significant improvement in their symptoms and significantly higher response rates compared to either haloperidol or placebo. A separate 12-week, multicenter, double-blind study enrolled 347 subjects with acute mania. Result demonstrated a significantly greater percentage of subjects responded to treatment with aripiprazole compared to patients treated with haloperidol at Week 12 (49.7% vs. 28.4%). Both studies were presented at the 156th Annual Meeting of the American Psychiatric Association.

June 2, 2003

AstraZeneca reported positive results from two-phase III studies investigating Seroquel, a previously approved schizophrenia drug, for the new indication of acute mania associated with bipolar disorder. Results showed that 48.1% of subjects treated with Seroquel achieved a response compared with 31.3% of those subjects given placebo. Response was defined as greater or equal to a 50% decrease from baseline YMRS (Young Mania Rating Scale) score. Data demonstrated that after three weeks of treatment, subjects treated with Seroquel had a YMRS score of -13.58 from baseline, compared with -7.76 in the placebo group. The two 12-week, double blind, randomized, placebo-controlled trials enrolled 604 subjects with bipolar disorder and was designed to assess the efficacy and safety of Seroquel monotherapy for the treatment of acute mania. Common adverse events in subjects receiving Seroquel included insomnia, dry mouth and somnolence. Results were presented at the 156th annual meeting of the American Psychiatric Association.

Lilly reported positive results from a phase IV trial investigating olanzapine, an antipsychotic for the treatment of bipolar disorder. Results showed the time to relapse of either mania or depression was significantly longer for olanzapine subjects than placebo-treated subjects (174 versus 22 days). Data also demonstrated that olanzapine-treated subjects had a significantly lower rate of overall mania (16.4%, olanzapine vs. 41.2%, placebo) or depression relapse (34.7% vs. 47.8%). In addition, significantly more olanzapine-treated subjects (23.6%) completed the 52-week trial than those on placebo (9.6%). The double blind, randomized, placebo-controlled study enrolled 361 subjects with bipolar disorder. Subjects received either olanzapine or placebo for 52 weeks after achieving remission during a six-to 12-week period of open-label treatment. Common adverse events for the olanzapine group were weight gain, fatigue and inner and outer restlessness.

November 11, 2002

AstraZeneca positive results from a phase IV clinical trial investigating Seroquel (quetiapine fumarate), in combination with traditional mood stabilization therapy (lithium or divalproex), on adolescents with bipolar disorder. The double blind, placebo-controlled, randomized clinical study evaluated the efficacy of Seroquel and divalproex as a combination therapy, versus divalproex alone, in 30 subjects ages 12 to 18. The data showed that 87% of the Seroquel combination group experienced a 50% reduction in the Young Mania Rating Scale (YMRS) scores, compared to 53% in the divalproex single therapy group. In addition, 86% of the Seroquel combination group showed improvement in the Clinical Global Impression (CGI) scores, compared to 53% in the divalproex single therapy group. Seroquel was shown to be well tolerated, with no subjects experiencing any extrapyramidal side effects (EPS), QTc prolongation or weight gain.

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.

May 28, 2002

Phase III study results indicate that treatment with Bristol-Myers Squibb and Otsuka Pharmaceutical's aripiprazole significantly improves symptoms of acute mania in subjects with bipolar disorder. The multicenter, double-blind, randomized, placebo-controlled trial included 262 subjects diagnosed with acute mania. The data demonstrated a rapid onset of action for the drug; beginning at day four, aripiprazole was significantly more effective than placebo in reducing manic symptoms. Forty percent of aripiprazole-treated subjects responded to treatment (defined as a decrease of greater than or equal to 50% in Y-MRS total score), compared to 19% of placebo-treated subjects.

This information does not represent a Lupus Research Institute endorsement of any listed study. It is merely a notice that the study is available. If you are presently under the care of a physician for lupus or other conditions, you should not disrupt your current program without discussing it with your doctor(s). Do not contact the Lupus Research Institute for information on these studies. Only contact the listed numbers. The Lupus Research Institute does not have any jurisdiction over or further involvement with these studies, other than to make people aware that they are being conducted.