Clinical Trials Resource Center

New Medical Therapies™

Depression (Major/Severe)

December 15, 2014

Otsuka Pharmaceutical and H. Lundbeck issued results of a phase III study of brexpiprazole as adjunctive treatment to antidepressant therapy (ADT) in patients with major depressive disorder (MDD). Patients with MDD who failed to reach adequate response during one to three treatment attempts with ADT were enrolled and received an additional trial with a (single-blind) ADT for eight weeks. Those patients who still failed to reach an adequate response throughout this phase were then randomized (double-blind) to ADT and brexpiprazole or ADT and placebo for six weeks. Adjunctive brexpiprazole showed greater improvement than adjunctive placebo in MADRS (Montgomery–Åsberg Depression Rating Scale) total score at week six in the efficacy population per final protocol in study 1 (2mg+ADT [N=175]: -3.21, p=0.0002), and in study 2 (1mg+ADT [N=211]: -1.30, p=0.0737; 3mg+ADT [N=213]: -1.95, p=0.0079). Similar results were observed for the efficacy population in both studies. Discontinuations due to adverse events were low across all groups (1mg = 1.3%, 2mg = 3.2%, 3mg = 3.5%, placebo = 0.7%) and only one patient discontinued due to lack of efficacy (in the brexpiprazole 1mg group). A NDA for brexpiprazole has been filed with the FDA and the PDUFA date is in July 2015.

November 24, 2014

Neuralstem released results of a phase Ib study of NSI-189 for major depressive disorder (MDD). In this single-site study, 24 patients with confirmed diagnosis of recurrent MDD were treated orally with NSI-189 in three equal dose cohorts (8/dose cohort; 40mg QD, 40mg BID and 40mg TID) for 28 days. Each dose cohort consisted of randomized, double-blinded, placebo controls at 1:3 ratio of placebo:drug. All subjects stayed in-clinic for the 28-day treatment period. After this period, the subjects returned to the clinic for follow-up measures for up to an additional eight weeks post-dosing. A significant number of patients on active treatment demonstrated clinical improvement by a reduction in total Montgomery-Asberg Depression Rating Scale (MADRS) scores >/= 15.9 points, which continued eight weeks after dosing stopped. The company plans to launch a large, multi-site, phase II study in the second quarter of 2015.

November 17, 2014

Pfizer reported results of a phase IV study of Pristiq Extended Release Tablets 50mg and 100mg doses v. placebo focused on sexual function in adult patients diagnosed with major depressive disorder (MDD). In the phase IV, multi-center, randomized, double-blind placebo-controlled study, a total of 924 patients, 18-years or older, with a baseline HAM-D17 score of ≥20, were randomly assigned to Pristiq 50mg/day, Pristiq 100 mg/ day or placebo in a 1:1:1 ratio over an eight-week period. The primary efficacy end point for the study was the change from baseline in HAM-D17 total score at week eight. Incidence of sexual dysfunction was assessed using the ASEX data. In adult outpatients with MDD with baseline sexual activity and at least one post-baseline assessment, effects on ASEX total and item scores were comparable for the Pristiq 50mg and Pristiq 100mg groups and placebo. Rates of sexual dysfunction were comparable between each Pristiq dose and placebo at baseline (placebo, 52%; Pristiq 50mg/d, 56%; Pristiq 100mg/d, 54%) and at week eight (placebo, 45%; Pristiq 50mg/d, 49%; Pristiq 100mg/d, 47%).

July 28, 2014

Neuralstem released result of a phase I study of NSI-189 for major depressive disorder (MDD). The single-site study enrolled 24 patients with confirmed diagnosis of recurrent MDD who were treated orally with NSI-189 in three equal dose cohorts (8/dose cohort; 40mg QD, 40mg BID, and 40mg TID) for 28 days. Each dose cohort consisted of randomized, double-blinded, placebo controls at 1:3 ratio of placebo: drug. In a comprehensive assessment scale for depression (Symptoms of Depression Questionnaire or SDQ), the combined treatment group showed statistically significant improvement (p=0.02) after 28 days of the drug treatment compared to its randomized, double-blinded, placebo control group. There was a large effect size of 0.90. As measured by the assessment scale of cognitive and functioning deficits specifically designed for depressed patients (Cognitive and Physical Functioning Questionnaire or CPFQ), the treatment group was significantly better than the placebo group (p=0.01) at Day 28 with a large effect size of 0.94. As measured by both by SDQ and CPFQ, NSI-189’s significant and large treatment effects continued for eight weeks, even after the drug was withdrawn. Neuralstem plans to launch a large, multi-site phase II study by the first quarter of 2015.

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.

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.

October 26, 2009

Targacept issued positive results from a phase IIb trial of TC-5214 for the treatment of Major Depressive Disorder. The design of this study included two phases. In the first phase 579 subjects diagnosed with MDD received first-line treatment with Celexa (standard of care) for eight weeks, 20mg daily for the first four weeks and 40mg daily for the next four weeks, to determine the extent of therapeutic response. Subjects who did not respond well based on predefined criteria at the end of eight weeks were randomized into the double blind second phase of the trial. These subjects (n≡265) continued to received Cerexa with add-on TC-5214 or placebo for an additional eight weeks. The daily dosage of TC-5214 was initially 2mg, with an option to be increased to 4mg and to 8mg based on response. The primary endpoint , change from baseline as measured by the Hamilton Depression Rating Scale (HAM-D), was reached with statistical significance on an intent-to-treat basis. The clinical response (change from double blind baseline after eight weeks) on HAM-D was 6.0 points greater for the add-on TC-5214 arm than for the add-on placebo arm (13.75 point improvement vs. 7.75 point improvement; p<0.0001). In addition, all of the secondary outcome measures, including the Montgomery-Asberg Depression Rating Scale, the Quick Inventory of Depressive Symptomatology Self Reporting scale and assessments of irritability, disability, cognition, severity of illness and global improvement, were reached with statistical improvement (p<0.0001 for all measures). TC-5214 exhibited a favorable tolerability profile.

July 27, 2009

Targacept reported positive results from a phase IIb trial of TC-5214 for the treatment of Major Depressive Disorder (MDD). This two-stage study was conducted across India and the US. In the first stage, 579 subjects with MDD received first-line treatment with citalopram hydrobromide (standard of care) for eight weeks; 20mg daily for the first four weeks and 40mg daily for the next four weeks. The subjects who did not respond well based on predefined criteria (n≡265) were randomized into the double blind second phase of the trial where they continued their citalopram treatment and also received either add-on TC-5214 or add-on placebo for an additional eight weeks. The initial daily dosage of TC-5214 was 2mg and could be increased to 8mg based on tolerability and therapeutic response. The primary outcome measure was mean change between treatment (TC-5214 + citalopram) and placebo (placebo + citalopram) from double blind baseline as measured by the Hamilton Depression Rating Scale (HAM-D) at week 16. This endpoint was reached with statistical significance in favor of TC-5214 (p<0.0001). All secondary endpoints, including assessments of depression, irritability, disability, cognition, severity of illness and global improvement, were also highly statistically significant in favor of TC-5214.

December 3, 2007

Forest Laboratories and H. Lundbeck released positive preliminary top-line results from a phase III trial of Lexapro for the treatment of Major Depressive Disorder in adolescents. This double-blind, parallel-group, placebo-controlled study enrolled three hundred and sixteen adolescent subjects, aged twelve to seventeen, in the US. The subjects received either Lexapro (10-20 mg) or placebo for eight weeks. The primary endpoint was change from baseline to week eight on the Children's Depression Rating Scale - Revised (CDRS-R). A statistically significant improvement was observed in the subjects treated with Lexapro when compared to placebo (p=0.022). Treatment was determined to be safe and well tolerated. Pending positive final results, Forest and H. Lundbeck plan to file for regulatory approval in 2008.

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.

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.

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.