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June 10, 2013
Alkermes reported results from a phase II trial of ALKS 5461 for the treatment of major depressive disorder (MDD). This randomized, double-blind, multicenter, placebo-controlled study involved two four-week stages run in-sequence that enrolled 142 patients with MDD who had an inadequate response to a stable dose of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). Two doses of ALKS 5461 were evaluated, each with a 1:1 ratio of buprenorphine and ALKS 33 (lower dose of 2mg/2mg and higher dose of 8mg/8mg). The trial met the primary endpoint, met key secondary endpoints and demonstrated significant reduction in depressive symptoms versus placebo. ALKS 5461 significantly reduced Hamilton Depression Rating Scale (HAM-D17) scores from baseline (p=0.013), with a reduction of 5.3 points, compared to a reduction of 1.2 points in the placebo group at the end of the four-week treatment period. ALKS 5461 also significantly reduced Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline (p=0.004), with a reduction of 8.7 points, compared to a reduction of 1.8 points in the placebo group at the end of the four-week treatment period. ALKS 5461 was well tolerated. The most common adverse events observed in the study were nausea, headache and dizziness. Alkermes plans to initiate clinical development.
April 29, 2013
Alkermes reported preliminary results from a phase II trial of ALKS 5461 for the treatment of major depressive disorder (MDD). This randomized, double-blind, multi-center, placebo-controlled study enrolled 142 patients with MDD who had an inadequate response to a stable dose of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). Subjects received one of two dosing regimens of oral ALKS 5461 or placebo for four weeks. Data showed ALKS 5461 significantly reduced depressive symptoms across a range of standard measures including the study’s primary outcome measure, the Hamilton Depression Rating Scale (HAMD17) (p=0.026), the Montgomery–Åsberg Depression Rating Scale (MADRS) (p=0.004) and the Clinical Global Impression–Severity Scale (CGI-S) (p=0.035). ALKS 5461 was well tolerated. Based on these results, and positive phase I/II results, Alkermes plans to request a meeting with the FDA and advance ALKS 5461 into a pivotal development program.
March 12, 2012
Forest Labs and Pierre Fabre Medicament issued results from a phase III trial of levomilnacipran for the treatment of major depressive disorder. This randomized, double-blind, placebo-controlled, flexible-dose study enrolled 442 adult subjects who received levomilnacipran 40-120 mg once daily or placebo for eight weeks. This was followed by an additional two-week double-blind down-taper period. The primary endpoint was a reduction on the Montgomery-Asberg Depression Rating Scale-Clinician Rated (MADRS-CR). The placebo corrected mean change from baseline to end of week eight was: -3.1 (p≡0.005). Statistically significant improvement was also seen in the Sheehan Disability scale (SDS), the pre-specified key secondary parameter (placebo corrected difference: -2.6, p≡0.001). Levomilnacipran was generally well-tolerated. The most common adverse events related to levomilnacipran were nausea, dizziness, and constipation.
January 9, 2012
Alkermes released results from a phase I/II trial of ALKS 5461 for major depressive disorder. This randomized, double-blind, placebo-controlled, parallel-group study enrolled 32 subjects who had an inadequate response to a stable dose of either a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor. The subjects received one of two sublingual dosing regimens of ALKS 5461 or placebo for seven days. In both dosing cohorts, subjects administered ALKS 5461 demonstrated greater reductions from baseline in depressive symptoms, as measured by the HAM-D17, compared to those administered placebo. In one dosing cohort, these differences in depressive severity were statistically significant. ALKS 5461 was generally well tolerated in both dosing cohorts.
July 25, 2011
Forest Laboratories and Pierre Fabre reported preliminary results from a phase III trial of levomilnacipran for major depressive disorder. This randomized, double-blind, placebo-controlled, fixed-dose study, LVM-MD-01, enrolled 700 outpatients who met the DSM-IV-TR criteria for major depressive disorder. The subjects received levomilnacipran oral capsules 40, 80 or 120 mg/day once daily or placebo for eight weeks. The primary endpoint was the change on the Montgomery-Asberg Depression Rating Scale- Clinician Rated (MADRS-CR) versus placebo from baseline to week eight. The primary endpoint was reached. The difference in the MADRS-CR total score was: -3.2 (p≡0.019), -4.0 (p≡0.004) and -4.9 (p<0.001) in 40, 80, 120 mg groups, respectively, versus placebo. Levomilnacipran was generally well-tolerated.
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.
February 18, 2008
Labopharm issued positive results from a phase III trial of Trazodone for the treatment of depression. This randomized, double-blind, two-arm, multi-center study, 04ACL3-001, enrolled four hundred and twelve subjects with major unipolar depressive disorder in the United States and Canada. The subjects received once-daily trazodone, or placebo, for eight weeks. Within the initial two-week titration period, subjects were titrated every three to four days to an optimal dose (maximum dose of 375 mg/day). They were than maintained at the optimal dose for the remainder of the study. The primary efficacy endpoint was to compare the change in the Hamilton Rating Scale for Depression (HAMD-17) total score from baseline to the end of the study between the two arms. This endpoint was reached with statistical significance in the Trazodone arm over placebo (p value of 0.0183). The dropout rate was 21% in the placebo group and 30.2% in the once-daily trazodone group, a rate comparable to drop out rates in other depression studies. Based on the results, Labopharm plans to file an NDA for this once-daily formulation of trazodone with the U.S. FDA later this year.
January 7, 2008
Schering Plough announced positive results from a clinical trial of asenapine for the treatment of schizophrenia. This trial enrolled four hundred and forty-eight adult subjects who received asenapine 5 mg twice daily, asenapine 10 mg twice daily, haloperidol 4 mg twice daily or placebo, for six weeks. The primary endpoint was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to day forty-two. The PANSS score was significantly better for the asenapine 5 mg, 10 mg and haloperidol arms versus placebo (-21.3, - 19.4, -20.0 and -14.6, respectively). Statistical significance was reached in a key secondary endpoint, PANSS positive subscale score, in the asenapine 5 mg, 10 mg and haloperidol arms versus placebo (-7.5, -6.9 and -7.3 vs. -5.0, respectively). In addition, significant changes were seen in the PANSS negative subscale score for the asenapine 5 mg, 10 mg and haloperidol arms (-4.5, -4.3 and -4.2 vs. -3.0, respectively) and on the PANSS general psychopathology subscale score (-9.6, -8.5 and -8.6 vs. -6.8, respectively). Significantly more subjects in both asenapine 5 mg and 10 mg, and haloperidol demonstrated reductions in PANSS total score of greater than or equal to 30% versus placebo (55%, 49% and 43% versus 33%, respectively). Changes on the Clinical Global Impression-Severity of Illness (CGI-S) scale for asenapine 5 mg and 10 mg, and haloperidol were higher than for placebo (-1.2 , -1.1 and -1.2 vs. -0.8, respectively). Treatment was generally safe and well tolerated. An NDA is currently under review by the FDA.
Vanda presented positive results from a phase III trial of iloperidone for the treatment of schizophrenia. This randomized, double-blind, placebo-controlled, multi-center, four-week inpatient study enrolled six hundred four subjects. Following fixed-dose titration, the subjects were randomized to receive iloperidone at 24 mg/day, ziprasidone at 160 mg/day, or placebo. The subjects treated with iloperidone had significantly greater improvements in Positive and Negative Syndrome Scale-Total (PANSS-T) scores than those on placebo and had PANSS-T improvement comparable to ziprasidone. Iloperidone was also associated with a favorable profile on the Extrapyramidal Symptoms Rating Scale (ESRS) versus placebo. In addition, iloperidone had a similar akathisia profile to placebo, while ziprasidone was associated with a 26% rate of worsening of akathisia compared to placebo on the Barnes Akathisia Scale (BAS). An NDA is currently under review by the FDA.
Wyeth announced results from two phase III trials of Prisitq for the treatment of depression. These identical multicenter, randomized, double-blind, placebo-controlled, eight-week studies enrolled four hundred and eighty-three adult subjects outside of the United States and four hundred and forty-seven subjects in the United States. Subjects in both trials received Prisitq at fixed doses of 50 mg/day and 100 mg/day. For the 100 mg/day group, the dose was increased from 50 mg/day to 100 mg/day on the eighth day of the study. The 50 mg/day dose of desvenlafaxine was associated with a significant reduction in the symptoms of Major Depressive Disorder as measured by the Hamilton Depression Scale (HAM-D17) scores over eight weeks compared with placebo (ex-US: p=0.002, 50 mg = -13.2, placebo = -10.7; U.S.: p=0.018, 50 mg = -11.5, placebo = -9.5). While the 100 mg/day dose showed a statistically significant improvement in the international study versus placebo (p<0.001, 100 mg = -13.7), this dose did not statistically separate from placebo in the U.S. study (p=0.065, 100 mg = -11.0). An NDA is currently under review by the FDA.
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.
August 20, 2007
DOV Pharmaceuticals announced positive results from a phase Ib trial of DOV 21,947 for the treatment of depression. This double-blind, placebo-controlled trial enrolled 46 subjects. Following a one-week placebo run-in, subjects received either escalating daily doses of 50 mg, 100 mg and 150 mg of DOV 21,947 or placebo, for eight weeks. The study demonstrated that DOV 21,947 was safe and well-tolerated in this dose range with no reported serious adverse events. In addition, DOV 21,947 treated subjects had lowered plasma triglyceride levels compared to placebo treated subjects (p<0.015). This reduction in mean triglyceride levels was observed following two weeks of treatment (~23% reduction), was maintained at the end of the DOV 21,947 treatment period (~29% reduction) and was reversed after the one-week washout period at the end of the study. Based on the results, DOV plans to initiate phase II trials on Q4 of 2007.
August 6, 2007
Intellect Neurosciences reported positive results from a phase I trial of OXIGON for the treatment of neurological disorders. This double-blind, randomized, placebo-controlled, single-escalating dose study enrolled 54 healthy elderly subjects. The trial was designed to determine the safety, tolerability and pharmacokinetics of OXIGON with and without food interactions. Treatment was shown to be safe and well tolerated, with no serious adverse events reported up to the highest single dose of 1.2 grams. Data from a phase Ib trial were expected shortly.
Phytopharm announced positive results from a phase Ib trial of Myogane for the treatment of Amyotrophic Lateral Sclerosis (ALS). This randomized, double blind, placebo-controlled, trial enrolled healthy subjects in the UK. Subjects received single escalating oral doses of Myogane. The study demonstrated good safety, tolerability and pharmacokinetic profiles, as well as an excellent absorption profile. The highest dose administered (640 mg) was well tolerated with no adverse events. Based on the results, Phytopharm plans to advance Myogane into phase II trials.
Targacept issued positive results from a phase II trial of mecamylamine HCL as add-on therapy for the treatment of depression. This trial, dubbed STAR*D (Sequenced Treatment Alternatives to Relieve Depression), enrolled 192 subjects in the US and India. All subjects were inadequate responders to first-line citalopram therapy. After a 3 to 5 day washout period, subjects were started on citalopram in an open label phase. . Citalopram therapy started at 20 mg once daily and was increased at week 2 to 40 mg once daily. This monotherapy lasted 6 weeks. After evaluation, those subjects considered inadequate responders were randomized in a double-blind fashion to receive either placebo or mecamylamine as an add-on to continued citalopram therapy, a combination known as TRIDMAC. Mecamylamine was started at 5 mg daily and could be increased to 7.5 mg after 2 weeks of treatment. After a further 2 weeks, medication could be increased to 10 mg. Results showed mecamylamine was superior to placebo, when added to subjects who were inadequate responders to first-line treatment with citalopram. Mecamylamine was also superior to placebo in treating symptoms of irritability. The treatment combination was generally well tolerated.
March 26, 2007
AstraZeneca issued positive results from two phase III trials of Seroquel SR for the treatment of schizophrenia. The first was a randomized, double-blind trial and enrolled 588 subjects who received Seroquel SR (400, 600 or 800 mg/day) or placebo for six weeks. By the end of treatment, significant improvements in the PANNS scores from baseline were observed for all treatment groups. Reductions of 24.8 (p=0.03), 30.9 (p>0.001), and 31.3 (p>0.001) points were seen with 400, 600, and 800 mg doses, respectively, compared with a reduction of 18.8 points for placebo. The second trial was a double-blind placebo controlled study and enrolled 197 subjects who received Seroquel SR at a mean dose of 669 mg/day, or placebo. This trial was designed to evaluate the time to first psychiatric relapse. When compared to placebo, Seroquel SR showed a reduced risk of relapse of 87% (p>0.0001) as well as a longer time to relapse. AstraZeneca filed a NDA with the FDA for Seroquel SR in July of 2006.
Corcept released negative results from a phase III trial of Corlux for the treatment of major depressive disorder. This randomized, double-blind, placebo-controlled trial enrolled 443 subjects in the US and Europe. Subjects received Corlux (300 mg, 600 mg and 1200 mg) or placebo, once daily for seven days. Subjects were off any antidepressant/antipsychotic medication for at least one week before the treatment period. Concomitant antidepressant therapy started on day 1 and lasted through day 56. The primary endpoint was responder analysis, 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. Statistical significance was not reached in the primary endpoint. However there was a significant correlation between plasma levels and clinical outcome achieved during treatment. Based on the combination of this and two other phase III results, Corcept plans to initiate a new phase III trial later in 2007.
March 19, 2007
CeNeRx issued positive results from a phase I trial of Tyrima for thetreatment of depression and anxiety. This single-dose, placebo-controlled trialenrolled 41 subjects who received Tyrima in doses escalating from 5 mg to 120mg. Treatment was safe and well tolerated up to the highest dose. Thepharmacokinetic profile was positive, showing that Tyrima reached high plasmaconcentrations that increased linearly with dose and the half-life shouldfavorability towards once or twice daily dosing. Based on the results, CeNeRxplans to move forward with multiple dose trials.
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.
October 3, 2005
DOV Pharmaceutical reported positive results of a phase II trial of their investigational triple-reuptake-inhibitor DOV 216,303 for the treatment of depression. Trial data indicated that the drug produced significant improvements relative to based line in symptom severity score on the HAM-D diagnostic scale (p<0.0001). These improvements were non-inferior to active control. No serious adverse events were noted, and to positive overall tolerability profile observed in earlier studies was maintained. This randomized, multicenter, double-blind, controlled study enrolled 67 patients, who received either 50 mg DOV 216,303 or 20 mg citalopram (an approved SSRI antidepressant), twice daily for 2 weeks.
July 4, 2005
Fabre-Kramer Pharmaceuticals issued positive results of a pair of phase III trials of their direct serotonin agonist gepirone ER, for the treatment of major depression. In the first study, gepirone produced a significant amelioration of depressive symptoms, as measured on the Hamilton Depression Scale (p=0.032). The second study yielded a trend towards rapid onset of action, with a non-significantly greater portion of subjects achieving symptom amelioration within 2 weeks, vs. placebo. In both trials, gepirone produced a significantly greater portion of patients experiencing a 50%-or-greater reduction in symptom severity compared to placebo. These double-blind, multi-center, randomized, placebo-controlled studies enrolled a combined total of 454 depressed patients. The company announced that these data would support amended NDA filing for the drug later this year.
January 18, 2005
Amarin Corporation has announced positive results of a phase IIa study of Miranox (LAX-101c), for the treatment of unresponsive major depression. Data from the first exploratory trial found that among subjects experiencing a new episode of depression, the drug produced a statistically significant improvement in symptoms on the Bech-Depression Scale over placebo, a standardized rating system for primary depressive symptomology. Retrospective analysis of a similar subset of patients from a previously completed trial with this methodology demonstrated a similarly significant efficacy profile. The placebo-controlled study randomized 77 subjects to receive either Miranox or placebo for 6 weeks; the previously completed study was a randomized, placebo-controlled trial which enrolled 70 subjects for 12 weeks.
Sepracor announced positive preliminary results of a phase IIIb/IV trial of their recently approved drug Lunesta (eszopiclone), for the treatment of insomnia in patients with co-morbid major depression. These data indicated that co-administration of Lunesta and fluoxetine (Prozac) significantly improved primary and secondary symptoms of insomnia vs. fluoxetine plus placebo, including sleep onset, wake time after sleep onset, and total sleep time (p<0.05). Furthermore, patients receiving Lunesta and fluoxetine experienced significant improvements in depression symptom severity and the proportion of patients achieving symptom response or remission vs. fluoxetine plus placebo, as measured by changes in total score on the HAM- D17 standardized scale. This double-blind, placebo-controlled ten-week study evaluated the efficacy and safety the drug in 545-patients who met DSM-IV(1) criteria for both insomnia and Major Depressive Disorder (depression). Subjects were randomized to receive either 3 mg Lunesta (n=270) or placebo (n=275) for eight weeks in addition to nightly fluoxetine, followed by a two-week Lunesta washout (fluoxetine treatment continued). Sepracor announced plans to present these data to the FDA, to discuss further development and expanded indications for the drug.
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.
July 28, 2003
Cyberonics reported positive results from a pivotal study and a companion study investigating vagus nerve stimulation (VNS Therapy) for the treatment of depression. Results from the pivotal study, called D-02, showed a highly statistically significant causal relationship between VNS Therapy and depression improvements from baseline observed in the companion study (D-04). One-year response rates, defined as at least a 50% improvement in depression symptoms as measured by the Hamilton Rating Scale were 21% and 30%, respectively in D-02 and 12% and 13%, respectively in D-04. One-year remission rates, defined as the percentage of subjects free of depressive symptoms after one year of treatment, were 16% and 17%, respectively in D-02 and 5% and 7%, respectively in D-04. The pivotal, double blind, randomized, placebo controlled 8-week enrolled 235 subjects. The long-term, observational, companion study enrolled 127 subjects with chronic or recurrent treatment resistant depression treated only with standard care.
January 21, 2003
Cyberonics reported positive results from a pivotal trial investigating their VNS Therapy, an experimental device for the treatment of depression. The results showed statistically and clinically significant improvements in Hamilton Rating Scale (HRSD-24) scores compared to baseline, the studies primary end point. Approximately 35% of acute treatment group subjects and 31% of all total subjects experienced at least a 50% improvement after one year of treatment. The HRSD-24 improvements observed over the first year of study were highly significant. Treatment involved a stopwatch-sized generator implanted in the left chest and a nerve stimulation electrode attached to the vagus nerve in the neck. Technicians then regulated electrical impulses through the vagus nerve 24 hours a day for 8 weeks. The study enrolled 180 subjects with chronic or recurrent treatment resistent depression at 13 sites in the U.S.