Efficacy, Safety, and Tolerability of Levomilnacipran ER in Pediatric Patients (7-17 Years) With Major Depressive Disorder

Major Depressive Disorder Clinical Trial

Official title:

A Double-blind, Placebo- and Active-controlled Evaluation of the Safety and Efficacy of Levomilnacipran ER in Pediatric Patients 7-17 Years With Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03569475
• Other study ID #: LVM-MD-14
• Status: Completed
• Phase: Phase 3
• Start date: July 6, 2018
• Est. completion date: March 1, 2021

Study information

• Verified date: March 2022
• Source: Allergan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 501
• Est. completion date: March 1, 2021
• Est. primary completion date: March 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Levomilnacipran ER
Levomilnacipran extended-release oral capsules
• Fluoxetine
Fluoxetine oral capsules
• Placebo
Matching placebo oral capsules

Locations

Country	Name	City	State
United States	Atlanta Behavioral Research, LLC	Atlanta	Georgia
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	BioBehavioral Research of Austin	Austin	Texas
United States	Houston Clinical Trials, LLC	Bellaire	Texas
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Care Access Research, Beverly Hills	Beverly Hills	California
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Ohio State University Department of Psychiatry	Columbus	Ohio
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	Millennium Center for Clinical Research	Creve Coeur	Missouri
United States	Roque Medical Trails LLC	Dallas	Texas
United States	iResearch Atlanta	Decatur	Georgia
United States	El Campo Clinical Trials	El Campo	Texas
United States	Mech Healthcare Associates	Frisco	Texas
United States	Behavioral Research Specialists, LLC	Glendale	California
United States	Advanced Research Institute of Miami	Homestead	Florida
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Red Oak Psychiatry Associates, PA	Houston	Texas
United States	Sun Valley Research Center	Imperial	California
United States	Clinical Neuroscience Solutions, Inc	Jacksonville	Florida
United States	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana
United States	Zynak Clinical	Lauderdale Lakes	Florida
United States	Northpointe Psychiatry	Lewisville	Texas
United States	Capstone Clinical Research	Libertyville	Illinois
United States	Alivation Research	Lincoln	Nebraska
United States	Woodland International Research Group	Little Rock	Arkansas
United States	Alliance Research	Long Beach	California
United States	Professional Psychiatric Services	Mason	Ohio
United States	Metroplex Pulmonary and Sleep Center	McKinney	Texas
United States	Advanced Clinical Research	Meridian	Idaho
United States	Columbus Clinical Services, LLC	Miami	Florida
United States	AMR Conventions Limited	Naperville	Illinois
United States	AMR-Baber Research, Inc.	Naperville	Illinois
United States	Manhattan Behavioral Medicine, PLLC	New York	New York
United States	Excell Research, Inc.	Oceanside	California
United States	IPS Research	Oklahoma City	Oklahoma
United States	NRC Research Institute	Orange	California
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	AIM Trials	Plano	Texas
United States	Finger Lake Clinical Research	Rochester	New York
United States	Rochester Center for Behavioral Medicine	Rochester Hills	Michigan
United States	Millennium Psychiatric Associates, LLC	Saint Louis	Missouri
United States	Clinical Trials of Texas, Inc. (CTT)	San Antonio	Texas
United States	Attalla Consultants, LLC	Smyrna	Georgia
United States	Clinical Research Institute	Stockbridge	Georgia
United States	Family Psychiatry of The Woodlands	The Woodlands	Texas
United States	Inova Clinical trials and Research Center	Tyrone	Georgia
United States	Children's National Health System	Washington	District of Columbia
United States	CincyScience	West Chester	Ohio
United States	KU Wichita Clinical Trial Unit	Wichita	Kansas
United States	Elite Clinical Trials, Inc.	Wildomar	California

Sponsors (1)

Lead Sponsor	Collaborator
Allergan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Children's Depression Rating Scale- Revised (CDRS-R)	The CDRS-R is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6-17 years. It contains 17 ordinally-scaled items that evaluate the 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.	Baseline (Week 0) to Week 8
Secondary	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 participant's current state of mental illness compared with MDD population. The participant was rated on a scale from 1 to 7, where 1=normal, not at all ill and 7=among the most extremely ill participants. Higher score indicates worsening of mental illness. A negative change from Baseline indicates improvement. MMRM was used for analysis.	Baseline (Week 0) to Week 8