Efficacy, Safety, and Tolerability of Levomilnacipran ER in Pediatric Patients (7-17 Years) With Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Levomilnacipran ER; Fluoxetine; Placebo
Intervention description: Levomilnacipran extended-release oral capsules; Fluoxetine oral capsules; Matching placebo oral capsules
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: 501.0
Sex: All
Minimum age: 7 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The objective of this study is to evaluate the efficacy, safety, and tolerability of
      levomilnacipran compared with placebo in pediatric outpatients (7-17 years) with major
      depressive disorder (MDD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must meet Diagnostic and statistical manual of mental disorders fifth edition
             (DSM-5) criteria for MDD, confirmed by Kiddie Schedule for Affective Disorders -
             Present and Lifetime (K-SADS-PL)

          -  Patients must have a score ≥ 40 on the Children's Depression Rating Scale-Revised
             (CDRS-R) at Visits 1 and 2

          -  Patients must have a Clinical Global Impressions-Severity (CGI-S) score ≥ 4 at Visits
             1 and 2

          -  Patients must have a caregiver who can and is willing to consent to be responsible for
             safety monitoring of the Patient, provide information about the patient's condition,
             oversee the administration of investigational product, and accompany the patients to
             all study visits

          -  Female patients of childbearing potential who are sexually active must agree to use a
             reliable method of contraception that will continue for the duration of the study and
             within 30 days following the end of study participation.

          -  A sexually active male patients must agree to use contraception as detailed below
             during the treatment period and for at least 30 days after the last dose of
             investigational product.

        Exclusion Criteria:

          -  DSM-5-based diagnosis of an axis I disorder other than MDD that is the primary focus
             of treatment.

          -  Prior diagnosis of mental retardation or amnestic or other cognitive disorders based
             on DSM-5 criteria

          -  Imminent risk of injuring self or others or causing damage to property as judged by
             the Investigator

          -  Suicide risk as determined by meeting either of the following criteria:

               -  Any suicide attempt within the past year

               -  Significant risk at Visit 1 (Screening) or Visit 2 (Baseline), as judged by the
                  Investigator based on the psychiatric interview or information collected in the
                  Columbia-Suicide Severity Rating Scale (C-SSRS) treatment-Related Criteria

          -  History of allergy, intolerance, or hypersensitivity to levomilnacipran, milnacipran,
             fluoxetine, or any other Selective serotonin reuptake inhibitors (SSRI) or Serotonin
             and norepinephrine reuptake inhibitors (SNRI) or known hypersensitivity to the
             investigational products' non-medicinal ingredients including gelatin and cellulose

          -  Patients requiring prohibited concomitant medication or herbal supplements that could
             not be discontinued or switched to an allowable alternative medication and stabilized
             for at least 2 weeks preceding Visit 2 (Baseline)

          -  Patients taking any psychoactive drug or psychoactive herbal remedy within 5
             half-lives before Baseline (Visit 2), Patients who have ever been treated with a depot
             antipsychotic must also be excluded

          -  Patients who have initiated or terminated psychotherapy or behavior therapy within1
             month before Visit 1 (Screening), or who plan to initiate or change such therapies
             during the course of the study Other Medical criteria

          -  A clinically significant disease state that, in the investigator's opinion, might
             indicate that the patients is unsuitable for the study

          -  Any cardiovascular disease or condition that is clinically significant, unstable, or
             decompensated.

          -  Hypo- or hyperthyroidism, unless stabilized on appropriate pharmacotherapy with no
             change in dosage for at least 3 months before Visit 1 (Screening)

          -  Any condition that would be expected to affect drug absorption (eg, gastric bypass
             surgery)

          -  History of seizure disorder (except simple childhood febrile seizures before age 5),
             unexplained syncope or black-out episodes, stroke, significant head injury, tumor of
             the central nervous system, or any other condition that predisposes the patient toward
             a risk for seizure

          -  History of drug or alcohol abuse or dependence within the past year

          -  Pregnant, breastfeeding, and/or planning to become pregnant and/or breastfeed during
             the study or within 30 days following the end of study participation

          -  Patients who are unable to swallow capsules

          -  Treatment with any investigational product within 3 months (or at least 5 half-lives,
             whichever is longer) of Visit 1. Treatment with any investigational product other than
             those provided by AGN during study participation will be a protocol violation, and the
             patient will be terminated from this study

          -  Employee or immediate relative of an employee of Allergan (AGN), any of its affiliates
             or partners, or of the study center

          -  Patients or patients whose parent/guardian/ legally authorized representative (LAR)
             and/or caregivers are unable to speak and understand English (or their native language
             if this can be accommodated by the site and is approved by the Sponsor) sufficiently
             to understand the nature of the study, to provide informed assent/consent, or to allow
             the completion of all study assessments

          -  Unable or unlikely to comply with the study protocol or are unsuitable for any other
             reason, Other Criteriaas judged by the Investigator