Safety and Efficacy of Levomilnacipran ER in Adolescent Participants With Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Placebo; Levomilnacipran; Fluoxetine
Intervention description: Matched over-encapsulated placebo capsules administered orally on Day 1 to Week 8.; Over-encapsulated levomilnacipran ER capsules administered orally on Day 1 to Week 8.; Over-encapsulated fluoxetine tablets administered orally on Day 1 to Week 8.
Intervention MeSH terms: Milnacipran; Fluoxetine; Levomilnacipran
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 552.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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