Purpose

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)

Condition

Eligibility

Eligible Ages
Between 7 Years and 17 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 patient 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 patient 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 patient 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

Other Criteria

- 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 AGN, any of its affiliates or partners, or of the study center Patients or patients whose parent/guardian/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, as judged by the Investigator

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Levomilnacipran ER
patients will take levomilnacipran 10 mg/day on Days 1-3, 20 mg/day on Days 4-7, and 40 mg/day during weeks 2 through 8 of the double blinded treatment and 40 mg/day for 2 days, and then levomilnacipran 20 mg/day for 5 days in the down-taper period. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day is permitted at Week 3 through 8 of the double blinded treatment. in the down-taper period. the patient will take levomilnacipran 40 mg/day for 2 days, and then levomilnacipran 20 mg/day for 5 days
  • Drug: Levomilnacipran ER
    During the double-blind treatment period, patients will take levomilnacipran 10 mg/day on Days 1-3, 20 mg/day on Days 4-7, and 40 mg/day during Weeks 2 through 8. Based on therapeutic response and tolerability, an additional dose increase to 80 mg/day is permitted at Week 3. During the down-taper period, patients will take levomilnacipran 40 mg/day for 2 days, and then levomilnacipran 20 mg/day for 5 days
Active Comparator
Fluoxetine 20 mg
Patients randomized to the Fluoxetine 20 mg arm will take Week 1, 10mg/day; week 2 through week 8, 20 mg/day
  • Drug: Fluoxetine
    During the double-blind treatment period, patients will take Fluoxetine 10 mg/day on Days 1-7, and then 20 mg/day during Weeks 2 through Week 8. During the down-taper period, patients will take Fluoxetine 10 mg/day for 7 days.
Placebo Comparator
Placebo
Patients randomized to the placebo arm will take placebo capsules once daily through week 8
  • Drug: Placebo
    Patients randomized to the placebo arm will take placebo capsules once daily

Recruiting Locations

Children's National and nearby locations

Children's National Health System
Washington, District of Columbia 20010
Contact:
Study Coordinator
202-476-2088

More Details

NCT ID
NCT03569475
Status
Recruiting
Sponsor
Allergan

Study Contact

Clinical Trials Registry Team
877‐277‐8566
IR‐CTRegistration@Allergan.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.