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January 26, 2015
Alkermes reported results of a phase III
study of ALKS 5461 for the adjunctive treatment
of major depressive disorder (MDD).
The randomized, double-blind, parallel-arm,
FORWARD-1 study evaluated the safety, tolerability
and efficacy of two titration schedules
of ALKS 5461 administered once daily
as adjunctive treatment in 66 patients with
MDD who had an inadequate response to
commonly prescribed drugs for depression,
including selective serotonin reuptake inhibitors
(SSRIs) or serotonin-norepinephrine
reuptake inhibitors (SNRIs). Patients were
assigned to either a one-week or two-week
titration schedule of oral ALKS 5461, for a
total treatment period of eight weeks. ALKS
5461 was generally well-tolerated in both of
the two titration schedules evaluated. The
exploratory efficacy analyses showed ALKS
5461 significantly reduced depressive symptoms
from baseline starting at week one and
continued to the end of the treatment period
at week eight in patients who received either
of the two titration schedules. The observed
changes from baseline were clinically meaningful
and statistically significant (p<0.001).
These data support the one-week titration
schedule being utilized in the core phase III
efficacy studies in the FORWARD program.
March 31, 2014
Forest Laboratories and Gedeon Richter
reported results of a phase IIb trial of
cariprazine as adjunctive treatment in adult
patients with major depressive disorder
(MDD) who have demonstrated an inadequate
response to antidepressant therapy
(ADT). The trial consisted of three treatment
groups, cariprazine 1mg/day-2mg/day +
ADT, cariprazine 2mg/day-4.5mg/day + ADT
and placebo + ADT. The international, multicenter,
randomized, double-blind, placebocontrolled,
eight-week phase IIb study had a total of 819
subjects aged 18 to 65. Statistically significant
improvement in the Montgomery-Asberg Depression
Rating Scale total score was observed
in the cariprazine 2mg/day-4.5mg/day + ADT
group relative to the placebo + ADT treatment
group (cariprazine 2mg/day-4.5mg/day +
ADT: -2.2, p=0.0114 and cariprazine
1mg/day-2mg/day + ADT: -0.9, p=0.2404) by
MMRM analysis. Across both cariprazine dose
groups the most common adverse events
(incidence ≥10% and greater than placebo)
were akathisia, nausea, insomnia, somnolence
September 10, 2007
Clinical Data reported positive results from a phase III trial of Vilazodone for the treatment of depression. This randomized, double-blind, placebo-controlled study enrolled 410 adult subjects with major depressive disorder. The trial achieved the primary endpoint of mean change from baseline in the Montgomery-Asberg Depression Rating Scale total score compared to placebo (p=.001). A key secondary endpoint, mean change from baseline on the Hamilton Depression Rating Scale versus placebo, was also reached (p=.022). Based on the results Clinical Data plans to meet with the FDA to discuss any additional NDA filing requirements.
Eli Lilly issued positive results from a phase II trial of LY2140023 for the treatment of psychosis and schizophrenia. This randomized, double-blind, placebo-controlled clinical trial enrolled 196 subjects with schizophrenia. Following a period of gradual removal of pre-trial antipsychotic medications, the subjects were assigned to LY2140023 (40 mg twice daily), olanzapine (15 mg daily) or placebo for four weeks. The trial was designed to determine the superiority of LY2140023 versus placebo; olanzapine was used as an active control. In the 118 subjects who completed treatment the primary endpoint was achieved. A statistically significant improvement in PANSS (Positive and Negative Syndrome Scale) total score over placebo was seen in both the LY2140023 and olanzapine groups (-20.8, P < 0.001; -26.7, P < 0.001; respectively). After four weeks of treatment, both the LY2140023 group and the olanzapine group demonstrated significantly greater response rates compared to the placebo group (32.0%, P < 0.001; 41.2%, P < 0.001 and 3.2%, respectively). In addition, a mean 0.51-kg weight reduction from baseline was observed in the LY2140023 arm. Treatment with LY2140023 was shown to be safe and well tolerated, with all reported adverse events mild to moderate in nature. Based on the results Eli Lilly plans to continue with the development of LY2140023.
September 5, 2006
Corcept Therapeutics reported negative results from the first of three phase III trials of Corlux for the treatment of Psychotic Major Depression. This randomized, double-blind, placebo-controlled trial had a primary endpoint of responder analysis, which was defined as the proportion of subjects with at least a 50% improvement in the Brief Psychiatric Rating Scale Positive Symptom Subscale (BPRS PSS) at Day 7 and Day 56. Of the subjects in the Corlux arm, 30.5% responded and of the subjects in the placebo arm, 28.6% responded (p value = .762). Results from the second of these phase III studies were expected in September of 2006 and results from the third study were expected by early 2007.
April 3, 2006
Acadia issued positive results of a phase II trial of ACP-103, for the treatment of Parkinson's disease patients with treatment-induced psychosis. This double-blind, placebo-controlled study enrolled 60 patients across sites in the US, who received once-daily doses of ACP-103 (20 mg, 40 mg or 60 mg, escalated on poor response) or placebo for 28 days, in addition to maintained stable dopamine replacement therapy. Trial data met their primary endpoint, producing no significant difference vs. placebo in motoric tolerability (no worsening of motor function on dosing), as measured on the Unified Parkinson's Disease Rating Scale (p=0.22). Secondary efficacy data were also positive, with ACP-103 producing reductions in psychotic symptom severity on two of three diagnostic measures (UPDRS Part I, p<0.05; SAPS relative change from baseline, p=0.05; SAPS total score vs. placebo, p<0.09). Also, subjects receiving the drug required fewer dose escalations than the placebo group (p<0.05), indicating efficacy at lower doses.
April 18, 2005
Neuro3d has announced positive results of a pair of phase II trial of their investigational antipsychotic ocaperidone, for the treatment of schizophrenia. Data from both studies yielded strong evidence of efficacy, with significant improvement in all primary efficacy measures, including both positive (e.g. hallucinations) and negative (e.g. social withdrawal, emotional flatness) symptom severity scores on the PANSS, BPRS and CGI diagnostic scales, vs. placebo. The drug also demonstrated non-inferiority of efficacy vs. an approved antipsychotic, and significant relative superiority in reducing drug-induced weight gain. The first trial, a double-blind, placebo-controlled safety and efficacy study, randomized 127 patients to receive dose ranging regimens of ocaperidone (0.1 mg-0.6 mg) or placebo daily for 8 weeks. The second was an active-controlled approved-therapy comparison study which enrolled 105 subjects, who received ocaperidone or an approved atypical antipsychotic for the treatment daily for 12 weeks. The company announced that these data would form the basis of phase III trials in the near future.
September 20, 2004
Acadia Pharmaceuticals has reported the results of a phase II study of their investigational drug ACP-103, in mitigating side effects caused by antipsychotic therapy. Data indicated that the drug met its primary endpoint, with a significant reduction in observed symptoms of haloperidol-induced akathisia (motor disturbance), and a significant reduction in the elevated serum prolactin levels (hyperprolactinemia) caused by haloperidol; hyperprolactinemia can cause sexual and menstrual disturbance, increase risk of osteoporosis, and promote mammary tissue formation in men. The double-blind, placebo-controlled study enrolled 18 healthy volunteers in Sweden, who received either a single high dose or lower daily dose regimen of ACP-103 following a single dose of haloperidol. Acadia announced plans to replicate this phase II protocol with other antipsychotics.<
Predix Pharmaceuticals announced positive results of two pilot studies of PRX-00023, their serotonin-1A (5HT1A) receptor agonist for the treatment of anxiety and depression. Both studies found that the drug was safe, and very well tolerated. Pharmacokinetic and pharmacodynamic analyses indicated that trial doses of the drug produced noteworthy increases in 5HT1A-receptor activation surrogates, and demonstrated an elimination half-life consistent with once-daily dosing. The first study was a phase I investigation enrolling healthy male volunteers, who received single doses of 10-60 mg; the second study was a phase I b investigation enrolling healthy male and female volunteers, who received once-daily 10-60 mg. doses of the drug for 28 days. Both studies were designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics or PRX-00023 treatment. Predix announced that phase II trials, as well as INDs for two additional drugs based upon the same platform, were planned for the next 8 months.
August 11, 2003
Acadia Pharmaceuticals reported positive results from a phase I trial investigating ACP-103, a 5-HT2A inverse agonist for the treatment of various neuropsychiatric conditions. Results demonstrated that ACP-103 was safe and well tolerated with dose proportional pharmacokinetics and a long half-life. Data also demonstrated that ACP-103 was well tolerated with no changes in cardiovascular and neurological function and no serious adverse events. The randomized, double blind, placebo-controlled, dose-escalation study enrolled 49 subjects and used both single-dose and multiple-dose regimens. The single-dose study evaluated five doses ranging from 20 to 300 mg and the multiple dose-escalation study evaluated oral doses of 50, 100, and 150 mg given once-daily for 14-days.
October 21, 2002
Positive Phase IV trial results were reported for Seroquel, a drug designed by AstraZeneca for the treatment of schizophrenia. Seroquel, which was previously approved in 1997, was investigated further as an alternative treatment for patients on other antipsychotic medications. This was a 12-week, international, multi-center, open-label study and was noncomparative. The trial examined the effects of switching to Seroquel in subjects who showed an inadequate response to previous antipsychotic treatment or who experienced severe side effects with those treatments. Results suggested that patients might benefit from switching to Seroquel if they experience an undesirable response from another antipsychotic treatment.