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

Key Inclusion Criteria:

1. Male or female outpatients;12-17 years of age

2. Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, TextRevision (DSM-IV-TR) criteria for Major Depressive Disorder (MDD) , confirmed byKiddie Schedule for Affective Disorders and Schizophrenia for School-AgeChildren--Present and Lifetime (K-SADS-PL)

3. Score ≥ 40 on the Children's Depression Rating Scale-Revised (CDRS-R) at Visits 1 and 2

4. Clinical Global Impressions-Severity (CGI-S) score ≥ 4 at Visits 1 and 2

5. Reliable caregiver

6. Physical examination, vital signs, clinical laboratory tests, and ECG normal or notclinically significant

Key Psychiatric Exclusion Criteria:

1. DSM-IV-TR-based diagnosis of an axis I disorder other than MDD that is the primaryfocus of treatment

2. Mental retardation or amnestic or other cognitive disorders

• 3. Significant suicide risk:

• Suicide attempt within the past year OR

• Investigator judgment (based on psychiatric interview and C-SSRS) Key Treatment-Related Exclusion Criteria:

1. Allergy, intolerance, or hypersensitivity to levomilnacipran, milnacipran,fluoxetine, or any other selective serotonin reuptake inhibitor (SSRI) orserotonin-norepinephrine reuptake inhibitors (SNRI)

2. Use of prohibited concomitant medication that cannot be discontinued Other Key Medical Exclusion Criteria:

3. Any current medical condition that might interfere with the conduct of the study,confound the interpretation of study results, or affect patient safety

4. Liver enzyme tests (aspartate aminotransferase) AST and/or alanine aminotransferase (ALT) > 2X the upper limit of normal (ULN)

5. Clinically significant cardiovascular disorders

6. Seizure disorder or risk of seizure

7. Drug or alcohol abuse or dependence (within the past year)

8. Positive urine drug screen or blood alcohol