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

Forest Laboratories

Status and phase: Completed; Phase 3

Conditions: Major Depressive Disorder

Treatments: Drug: Placebo; Drug: Levomilnacipran; Drug: Fluoxetine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02431806

LVM-MD-11

Details and patient eligibility

About

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.

Full 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.

Enrollment: 552 patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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552 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

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.

Treatment:

Drug: Placebo

Levomilnacipran 40 mg

Experimental group

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.

Treatment:

Drug: Levomilnacipran

Levomilnacipran 80 mg

Experimental group

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.

Treatment:

Drug: Levomilnacipran

Fluoxetine 20 mg

Active Comparator group

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.

Treatment:

Drug: Fluoxetine