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

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Levomilnacipran
Fluoxetine
Sponsored by
Forest Laboratories
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

12 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Harmonex, Inc
  • University of Arizona Department of Psychiatry
  • Advanced Research Center, Inc.
  • ProScience Research Group
  • Sun Valley Research Center
  • Alliance for Research
  • Asclepes Research Centers
  • Syrentis Clinical Research
  • Pacific Clinical Research Medical Group
  • MCB Clinical Research Center
  • Florida Clinical Research Center; LLC
  • Coastal Clinical Research Specialists
  • Gulfcoast Clinical Research Center
  • Research in Miami Inc
  • Advanced Research Institute of Miami
  • Clinical Neuroscience Solutions, Inc.
  • Innovative Clinical Research, Inc.
  • Medical Research Group of Central Florida
  • Clinical Neuroscience Solutions, Inc.
  • University of South Florida Board of Trustee
  • Atlanta Center for Medical Research
  • Institute for Behavioral Medicine
  • Clinical Research Institute
  • Sandeep Gaonkar, MD
  • NeuroMedical Institute
  • Kentucky Pediatric Research
  • Adams Clinical Trials, LLC
  • Alivation Research
  • Kolade Research Institute
  • Healthy Perspectives - Innovative Mental Health Services. PLLC
  • Princeton Medical Institute
  • Manhattan Behavioral Medicine
  • Midwest Clinical Research Center
  • Professional Psychiatric Services
  • IPS Research Company
  • Sooner Clinical Research
  • Cutting Edge Research Group
  • Paradigm Research Professionals
  • Tulsa Clinical Research, LLC
  • Oregon Center for Clinical Investigations, Inc.
  • UTHSC-Houston
  • Bay Area Clinical Services dba Earle Research
  • Red Oak Psychiatry Associates
  • Family Psychiatry of The Woodlands
  • UVA Child and Family Psychiatry Clinic
  • Carilion Medical Center
  • Northwest Clinical Research Center
  • Eastside Therapeutic Resource dba Core Clinical
  • INSPIRA Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Active Comparator

Arm Label

Placebo

Levomilnacipran 40 mg

Levomilnacipran 80 mg

Fluoxetine 20 mg

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
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

Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale
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.

Full Information

First Posted
April 28, 2015
Last Updated
August 19, 2020
Sponsor
Forest Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT02431806
Brief Title
Safety and Efficacy of Levomilnacipran ER in Adolescent Participants With Major Depressive Disorder
Official Title
A Double-blind, Placebo- and Active-Controlled Evaluation of the Safety and Efficacy of Levomilnacipran ER in Adolescent Patients With Major Depressive Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
June 23, 2015 (Actual)
Primary Completion Date
August 19, 2019 (Actual)
Study Completion Date
August 19, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Forest Laboratories

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
552 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Levomilnacipran 40 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Levomilnacipran 80 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Fluoxetine 20 mg
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched over-encapsulated placebo capsules administered orally on Day 1 to Week 8.
Intervention Type
Drug
Intervention Name(s)
Levomilnacipran
Other Intervention Name(s)
Fetzima
Intervention Description
Over-encapsulated levomilnacipran ER capsules administered orally on Day 1 to Week 8.
Intervention Type
Drug
Intervention Name(s)
Fluoxetine
Other Intervention Name(s)
Prozac
Intervention Description
Over-encapsulated fluoxetine tablets administered orally on Day 1 to Week 8.
Primary Outcome Measure Information:
Title
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
Description
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.
Time Frame
Baseline (Week 0) to Week 8
Secondary Outcome Measure Information:
Title
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale
Description
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.
Time Frame
Baseline (Week 0) to Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Radecki
Organizational Affiliation
Forest Research Institute, Inc., an affiliate of Allergan, plc
Official's Role
Study Director
Facility Information:
Facility Name
Harmonex, Inc
City
Dothan
State/Province
Alabama
ZIP/Postal Code
36303
Country
United States
Facility Name
University of Arizona Department of Psychiatry
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Advanced Research Center, Inc.
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
ProScience Research Group
City
Culver City
State/Province
California
ZIP/Postal Code
90230
Country
United States
Facility Name
Sun Valley Research Center
City
Imperial
State/Province
California
ZIP/Postal Code
92251
Country
United States
Facility Name
Alliance for Research
City
Long Beach
State/Province
California
ZIP/Postal Code
90807
Country
United States
Facility Name
Asclepes Research Centers
City
Panorama City
State/Province
California
ZIP/Postal Code
91402
Country
United States
Facility Name
Syrentis Clinical Research
City
Santa Ana
State/Province
California
ZIP/Postal Code
97025
Country
United States
Facility Name
Pacific Clinical Research Medical Group
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
MCB Clinical Research Center
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80910
Country
United States
Facility Name
Florida Clinical Research Center; LLC
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34201
Country
United States
Facility Name
Coastal Clinical Research Specialists
City
Fernandina Beach
State/Province
Florida
ZIP/Postal Code
32034
Country
United States
Facility Name
Gulfcoast Clinical Research Center
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33912
Country
United States
Facility Name
Research in Miami Inc
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
Facility Name
Advanced Research Institute of Miami
City
Homestead
State/Province
Florida
ZIP/Postal Code
33030
Country
United States
Facility Name
Clinical Neuroscience Solutions, Inc.
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Innovative Clinical Research, Inc.
City
Lauderhill
State/Province
Florida
ZIP/Postal Code
33319
Country
United States
Facility Name
Medical Research Group of Central Florida
City
Orange City
State/Province
Florida
ZIP/Postal Code
32763
Country
United States
Facility Name
Clinical Neuroscience Solutions, Inc.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
Facility Name
University of South Florida Board of Trustee
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Atlanta Center for Medical Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30331
Country
United States
Facility Name
Institute for Behavioral Medicine
City
Smyrna
State/Province
Georgia
ZIP/Postal Code
30080-2620
Country
United States
Facility Name
Clinical Research Institute
City
Stockbridge
State/Province
Georgia
ZIP/Postal Code
30281
Country
United States
Facility Name
Sandeep Gaonkar, MD
City
Naperville
State/Province
Illinois
ZIP/Postal Code
60563
Country
United States
Facility Name
NeuroMedical Institute
City
Panama City
State/Province
Illinois
ZIP/Postal Code
32405
Country
United States
Facility Name
Kentucky Pediatric Research
City
Bardstown
State/Province
Kentucky
ZIP/Postal Code
40004
Country
United States
Facility Name
Adams Clinical Trials, LLC
City
Watertown
State/Province
Massachusetts
ZIP/Postal Code
02472
Country
United States
Facility Name
Alivation Research
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68526
Country
United States
Facility Name
Kolade Research Institute
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89102
Country
United States
Facility Name
Healthy Perspectives - Innovative Mental Health Services. PLLC
City
Nashua
State/Province
New Hampshire
ZIP/Postal Code
03060
Country
United States
Facility Name
Princeton Medical Institute
City
Princeton
State/Province
New Jersey
ZIP/Postal Code
08540
Country
United States
Facility Name
Manhattan Behavioral Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10036
Country
United States
Facility Name
Midwest Clinical Research Center
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
Professional Psychiatric Services
City
Mason
State/Province
Ohio
ZIP/Postal Code
45040
Country
United States
Facility Name
IPS Research Company
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73106
Country
United States
Facility Name
Sooner Clinical Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Cutting Edge Research Group
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73116
Country
United States
Facility Name
Paradigm Research Professionals
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73118
Country
United States
Facility Name
Tulsa Clinical Research, LLC
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Oregon Center for Clinical Investigations, Inc.
City
Salem
State/Province
Oregon
ZIP/Postal Code
97301
Country
United States
Facility Name
UTHSC-Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77054
Country
United States
Facility Name
Bay Area Clinical Services dba Earle Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77058
Country
United States
Facility Name
Red Oak Psychiatry Associates
City
Houston
State/Province
Texas
ZIP/Postal Code
77090
Country
United States
Facility Name
Family Psychiatry of The Woodlands
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77381
Country
United States
Facility Name
UVA Child and Family Psychiatry Clinic
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Carilion Medical Center
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24014
Country
United States
Facility Name
Northwest Clinical Research Center
City
Bellevue
State/Province
Washington
ZIP/Postal Code
98007
Country
United States
Facility Name
Eastside Therapeutic Resource dba Core Clinical
City
Everett
State/Province
Washington
ZIP/Postal Code
98201
Country
United States
Facility Name
INSPIRA Clinical Research
City
San Juan
ZIP/Postal Code
00918
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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