Safety and Efficacy of Levomilnacipran ER in Adolescent Participants With Major Depressive Disorder
- Conditions
- Major Depressive Disorder
- Interventions
- Registration Number
- NCT02431806
- Lead Sponsor
- Forest Laboratories
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 552
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received 2 dose matched over-encapsulated placebo capsules, once daily, orally during the Double-blind Treatment Period up to 8 weeks followed by a 1 week Taper-down Period if applicable as determined by the investigator. Levomilnacipran 40 mg Levomilnacipran Participants received over-encapsulated levomilnacipran extended release (ER) 40 mg/day capsules orally starting at a dose of 10 mg/day on Day 1-2, 20 mg/day on Days 3-7 and 40 mg/day on Week 2 through Week 8 during the Double-Blind Treatment Period, followed by a 1-week Double-Blind Taper-down Period if applicable as determined by the investigator. Participants received 1 dose matched placebo capsule each day to maintain the blind. Fluoxetine 20 mg Fluoxetine Participants received over-encapsulated fluoxetine 20 mg/day tablets orally starting at a dose of 10 mg/day in Week 1 and 20 mg/day in Week 2 through Week 8 during the Double-blind Treatment Period, followed by a 1-week Double-blind Taper-down Period if applicable as determined by the investigator. Participants received 1 dose matched placebo capsule each day to maintain the blind. Levomilnacipran 80 mg Levomilnacipran Participants received over-encapsulated levomilnacipran ER two 40 mg/day capsules (80 mg/day) orally starting at a dose of 10 mg/day on Day 1-2, 20 mg/day on Day 3-4, 40 mg/day on Day 5-7 and 80 mg/day on Week 2 through Week 8 during the Double-blind Treatment Period, followed by a 1-week Double-blind Taper-down Period if applicable as determined by the investigator. Participants received 1 dose matched placebo capsule the first week and during the taper-down period to maintain the blind.
- Primary Outcome Measures
Name Time Method Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score Baseline (Week 0) to Week 8 CDRS-R is a 17-item scale measuring presence and severity of symptoms commonly associated with childhood depression and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. The CDRS-R total score ranges from 17 to 113; higher score indicates more severe depression. A negative change from Baseline indicates improvement. Mixed Model for Repeated Measures (MMRM) was used for analysis.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Baseline (Week 0) to Week 8 The CGI-S is a clinician-rated scale used to rate the severity of the participants current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1= Very much improved; 2= Much improved; 3= Minimally improved; 4= No change; 5= Minimally worse; 6= Much worse; 7= Very much worse. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analysis.
Trial Locations
- Locations (48)
Innovative Clinical Research, Inc.
🇺🇸Lauderhill, Florida, United States
Professional Psychiatric Services
🇺🇸Mason, Ohio, United States
Carilion Medical Center
🇺🇸Roanoke, Virginia, United States
Atlanta Center for Medical Research
🇺🇸Atlanta, Georgia, United States
Medical Research Group of Central Florida
🇺🇸Orange City, Florida, United States
Adams Clinical Trials, LLC
🇺🇸Watertown, Massachusetts, United States
Pacific Clinical Research Medical Group
🇺🇸Upland, California, United States
Advanced Research Institute of Miami
🇺🇸Homestead, Florida, United States
Asclepes Research Centers
🇺🇸Panorama City, California, United States
Alivation Research
🇺🇸Lincoln, Nebraska, United States
UVA Child and Family Psychiatry Clinic
🇺🇸Charlottesville, Virginia, United States
Syrentis Clinical Research
🇺🇸Santa Ana, California, United States
MCB Clinical Research Center
🇺🇸Colorado Springs, Colorado, United States
Sandeep Gaonkar, MD
🇺🇸Naperville, Illinois, United States
INSPIRA Clinical Research
🇵🇷San Juan, Puerto Rico
Kentucky Pediatric Research
🇺🇸Bardstown, Kentucky, United States
Harmonex, Inc
🇺🇸Dothan, Alabama, United States
ProScience Research Group
🇺🇸Culver City, California, United States
University of Arizona Department of Psychiatry
🇺🇸Tucson, Arizona, United States
Sun Valley Research Center
🇺🇸Imperial, California, United States
Florida Clinical Research Center; LLC
🇺🇸Bradenton, Florida, United States
Coastal Clinical Research Specialists
🇺🇸Fernandina Beach, Florida, United States
Gulfcoast Clinical Research Center
🇺🇸Fort Myers, Florida, United States
Research in Miami Inc
🇺🇸Hialeah, Florida, United States
Institute for Behavioral Medicine
🇺🇸Smyrna, Georgia, United States
Clinical Research Institute
🇺🇸Stockbridge, Georgia, United States
NeuroMedical Institute
🇺🇸Panama City, Illinois, United States
Princeton Medical Institute
🇺🇸Princeton, New Jersey, United States
Healthy Perspectives - Innovative Mental Health Services. PLLC
🇺🇸Nashua, New Hampshire, United States
Manhattan Behavioral Medicine
🇺🇸New York, New York, United States
Midwest Clinical Research Center
🇺🇸Dayton, Ohio, United States
Tulsa Clinical Research, LLC
🇺🇸Tulsa, Oklahoma, United States
Oregon Center for Clinical Investigations, Inc.
🇺🇸Salem, Oregon, United States
Northwest Clinical Research Center
🇺🇸Bellevue, Washington, United States
Family Psychiatry of The Woodlands
🇺🇸The Woodlands, Texas, United States
Eastside Therapeutic Resource dba Core Clinical
🇺🇸Everett, Washington, United States
Alliance for Research
🇺🇸Long Beach, California, United States
Advanced Research Center, Inc.
🇺🇸Anaheim, California, United States
IPS Research Company
🇺🇸Oklahoma City, Oklahoma, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸Orlando, Florida, United States
Kolade Research Institute
🇺🇸Las Vegas, Nevada, United States
University of South Florida Board of Trustee
🇺🇸Tampa, Florida, United States
Sooner Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
Cutting Edge Research Group
🇺🇸Oklahoma City, Oklahoma, United States
UTHSC-Houston
🇺🇸Houston, Texas, United States
Paradigm Research Professionals
🇺🇸Oklahoma City, Oklahoma, United States
Bay Area Clinical Services dba Earle Research
🇺🇸Houston, Texas, United States
Red Oak Psychiatry Associates
🇺🇸Houston, Texas, United States