A Double-blind, Placebo- and Active-Controlled Evaluation of the Safety and Efficacy of Levomilnacipran ER in Adolescent Patients With Major Depressive Disorder
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 552
- 试验地点
- 48
- 主要终点
- Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
Levomilnacipran 40 mg
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.
干预措施: Levomilnacipran (Drug)
Levomilnacipran 80 mg
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.
干预措施: Levomilnacipran (Drug)
Fluoxetine 20 mg
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.
干预措施: Fluoxetine (Drug)
结局指标
主要结局
Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score
时间窗: 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.
次要结局
- Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale(Baseline (Week 0) to Week 8)