Safety and Efficacy of Levomilnacipran ER in Adolescent Participants With Major Depressive Disorder

A Double-blind, Placebo- and Active-Controlled Evaluation of the Safety and Efficacy of Levomilnacipran ER in Adolescent Patients With Major Depressive Disorder

The purpose of this study is to evaluate the efficacy, safety, and tolerability of levomilnacipran ER relative to placebo in adolescent outpatients (12-17 years) with Major Depressive Disorder (MDD). In addition, the study is designed to obtain pharmacokinetics (PK) data to guide dose selection for future pediatric studies of levomilnacipran.

Study LVM-MD-11 is a randomized, double-blind, placebo- and active-controlled, parallel group, fixed-dose study in adolescent patients, ages 12-17 years. The study will be approximately 10 weeks in duration:

• 1-week screening/washout period
• 8-week double-blind treatment period
• 1-week double-blind down-taper period

Participants who meet the eligibility criteria at Visit 2 (Baseline) will be randomized to 1 of 4 treatment groups: placebo, levomilnacipran 40 mg/day, levomilnacipran 80 mg/day, or fluoxetine 20 mg/day.

Key Inclusion Criteria:

• Male or female outpatients;12-17 years of age
• Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for MDD, confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime (K-SADS-PL)
• Score ≥ 40 on the Children's Depression Rating Scale-Revised (CDRS-R) at Visits 1 and 2
• Clinical Global Impressions-Severity (CGI-S) score ≥ 4 at Visits 1 and 2
• Reliable caregiver
• Physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG) normal or not clinically significant

Key Psychiatric Exclusion Criteria:

• DSM-IV-TR-based diagnosis of an axis I disorder other than MDD that is the primary focus of treatment
• Mental retardation or amnestic or other cognitive disorders
• Significant suicide risk:
• Suicide attempt within the past year OR
• Investigator judgment (based on psychiatric interview and Columbia-Suicide Severity Rating Scale (C-SSRS))

Key Treatment-Related Exclusion Criteria:

• Allergy, intolerance, or hypersensitivity to levomilnacipran, milnacipran, fluoxetine, or any other selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)
• Use of prohibited concomitant medication that cannot be discontinued

Other Key Medical Exclusion Criteria:

• Any current medical condition that might interfere with the conduct of the study, confound the interpretation of study results, or affect participants safety
• Liver enzyme tests aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2X the upper limit of normal (ULN)
• Clinically significant cardiovascular disorders
• Seizure disorder or risk of seizure
• Drug or alcohol abuse or dependence (within the past year)
• Positive urine drug screen or blood alcohol