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A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40-120?mg/day) in patients with major depressive disorder.

ABSTRACT: OBJECTIVE:Levomilnacipran ER is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD). Efficacy and safety have been evaluated in five Phase II/III studies, four of which met the pre-specified primary efficacy outcome. Results of the negative trial (ClinicalTrials.gov NCT00969150) are reported here. METHODS:A Phase III randomized, double-blind, placebo-controlled trial comparing flexible-dose levomilnacipran ER 40-120?mg/day with placebo was conducted in outpatients with MDD. Patients met the DSM-IV-TR criteria for MDD, had a current episode of depression of at least 4 weeks' duration, and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ?30. The study comprised a 1-week, single-blind, placebo lead-in, 8-week double-blind treatment, and a 2-week down-taper. The primary and secondary efficacy measures were change from baseline to Week 8 in MADRS and Sheehan Disability Scale (SDS) total scores, respectively, analyzed using a mixed-effects model for repeated measures approach. Safety outcomes included adverse events (AEs), laboratory and vital sign measures, the Columbia-Suicide Severity Rating Scale, and the Arizona Sexual Experiences Scale (ASEX). RESULTS:Three hundred and fifty-five patients received the study drug and had ?1 post-baseline MADRS total score assessment (ITT Population); 81.9% of placebo and 77.1% of levomilnacipran ER patients completed the study. For levomilnacipran ER vs placebo, MADRS (-15.7 vs -14.2) and SDS (-8.8 vs -8.2) total score improvements, and rates of MADRS response (38.5% vs 34.8%) and remission (25.3% vs 23.8%) were numerically greater but differences were not statistically significant. Levomilnacipran ER was generally well tolerated. More levomilnacipran ER patients vs placebo reported AEs; the most common AEs for levomilnacipran ER were nausea (17%) and headache (16%). Mean changes in most safety measures were small and similar between groups. There were no meaningful differences in total ASEX scores between groups. LIMITATIONS:Short duration of treatment, inclusion and exclusion criteria, and lack of an active comparator. CONCLUSION:Numerical improvements for levomilnacipran ER vs placebo were detected in this study, but the differences were not statistically significant; levomilnacipran ER was generally well tolerated.

SUBMITTER: Gommoll CP

PROVIDER: S-EPMC4937636 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40-120 mg/day) in patients with major depressive disorder.

Gommoll Carl P CP Greenberg William M WM Chen Changzheng C

Journal of drug assessment 20140116 1

<h4>Objective</h4>Levomilnacipran ER is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD). Efficacy and safety have been evaluated in five Phase II/III studies, four of which met the pre-specified primary efficacy outcome. Results of the negative trial (ClinicalTrials.gov NCT00969150) are reported here.<h4>Methods</h4>A Phase III randomized, double-blind, placebo-controlled trial comparing flexible-dose lev ...[more]

PMID: 27536449

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Project description:OBJECTIVE:Major depressive disorder is often chronic, with relapse and recurrence common. Levomilnacipran extended-release is a potent and selective serotonin and reuptake inhibitor approved in the United States for treatment of major depressive disorder in adults. The objective of this study (NCT01085812) was to evaluate the efficacy, safety, and tolerability of levomilnacipran extended-release in the prevention of relapse in patients with major depressive disorder. DESIGN:A 24-week Phase III randomized, double-blind, controlled trial comparing levomilnacipran extended-release 40-120mg/day with placebo for relapse prevention in patients with major depressive disorder who had responded to 12-week, open-label treatment with levomilnacipran extended-release. Statistical power was calculated on the assumption that 38 percent of placebo and 20 percent of levomilnacipran extended-release patients would relapse. SETTING:Thirty-six outpatient study centers throughout the United States and Canada. PARTICIPANTS:Of 348 patients who met randomization criteria and entered double-blind treatment, three discontinued prior to treatment, 112 were randomized to placebo, and 233 to levomilnacipran extended-release. MEASUREMENTS: PRIMARY OUTCOME:Time to relapse was analyzed using the Cox proportional hazard-regression model with treatment group and baseline Montgomery-Åsberg Depression Rating Scale score as explanatory variables. Safety was also evaluated. RESULTS:Time to relapse was longer for levomilnacipran extended-release versus placebo (hazard ratio [95% confidence interval] = 0.68 [0.40][1.17]), but the treatment difference was not statistically significant (P=0.165). A relatively low percentage of patients from either group relapsed (placebo=20.5%, levomilnacipran extended-release=13.9%). CONCLUSION:This study did not detect between-treatment group differences, potentially due to lower than expected relapse rates in the placebo group. Levomilnacipran extended-release was generally well tolerated.

Dataset Information

A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40-120?mg/day) in patients with major depressive disorder.

Publications

A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40-120 mg/day) in patients with major depressive disorder.

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