Phase IV:Safety and Efficacy of EMSAM in Adolescents With Major Depression

Study Overview
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Brief Summary
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The primary purpose of your participation in this study is to help answer the following research question: Whether 12-week administration of EMSAM (selegiline transdermal system) is safe and effective for the treatment of adolescents (aged 12 through 17 years) with Major Depressive Disorder (MDD).

Detailed Description
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• Assess the safety and efficacy of EMSAM (selegiline transdermal system) versus placebo in adolescents (aged 12 through 17 years) who meet criteria for Major Depressive Disorder (MDD) without psychotic features, single or recurrent

Official Title
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A Phase IV, Double-Blind, Placebo-Controlled, Randomized, Flexible Dose Study of the Safety and Efficacy of EMSAM in Adolescents With Major Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Selegiline Transdermal System
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male / Female outpatients 12 to 17 years of age diagnosed with Major Depressive Disorder (MDD). (Must have a Children's Depression Rating Scale-Revised [CDRS-R] with a total score of at least 45 at screening.) Female patients must test negative on a pregnancy at visit 1. Weight and height must be greater than the 10th percentile according to age and height, Assent and consent must be given. Exclusion Criteria: Have a serious or unstable medical illness, psychological condition, clinically significant laboratory or ECG result, hypersensitivity to selegiline, or any other condition that in the opinion of the investigator would compromise participation in the study or be likely to lead to hospitalization during the course of the study. Have a current or previous diagnosis of bipolar disorder, psychotic depression, schizophrenia or other psychotic disorder, anorexia, bulimia, obsessive compulsive disorder, pervasive development disorder or borderline personality disorder, as determined by the investigator. Have a risk of suicide Female patients who are either pregnant, nursing or have recently given birth. Use of any protocol prohibited medications or substances.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EMSAM<br>Approved Medication for Major Depressive Disorder: EMSAM (Selegiline Transdermal System) 6mg, 9mg, or 12mg | Drug: Selegiline Transdermal System<br>* EMSAM 6mg, 9mg, or 12mg Flexible Dose- 1 patch/24 hours- 12 Week Study<br>* Other names: EMSAM;|
| Placebo Comparator: Placebo<br>Placebo Selegiline Transdermal System 6, 9 or 12 | Drug: Placebo<br>* Matching Placebo for EMSAM 6mg, 9mg, or 12mg Flexible Dose- 1 patch/24 hours- 12 Week Study<br>* Other names: Matching Placebo Transdermal System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDRS-R Total Score (Child) (mITT w/LOCF Population) Week 12 | A summary of the primary efficacy outcome measure, Children's Depression Rating Scale (CDRS-R) Total Score, as reported by the Child, at Week 12 (EOS), by treatment assigned, is shown for the modified intent-to-treat (mITT) population, with the last observation carried forward (LOCF) in time. CDRS-R total raw scores range from 17(minimum) 113(maximum). A lower score indicates a lower likelihood of a depressive disorder, a higher score indicates a higher likelihood of a depressive disorder. Two subscales are summed to calculate a total score: Evaluated Symptom Area and Ratings of Observed Nonverbal Behavior. | baseline and 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGI-S - Week 12 (mITT w/LOCF Population) | A summary of the Clinical Global Impression of Severity (CGI-S) at baseline and Week 12 (EOS), by treatment assigned, is shown for the mITT population with LOCF. The CGI-s is the clinician's assessment of severity of illness (depression). Scores range from 1(minimum) to 7(maximum). A lower score indicates lower illness severity, a higher score indicates higher levels of illness severity. | Baseline and 12 Weeks | 
| CGI-C - Week 12 (mITT w/LOCF Population) | A summary of the Clinicians Global Impression of Change (CGI-C) Score at Week 12 (EOS), by treatment assigned, is shown for the mITT population with LOCF. The CGI-c assesses the overall change in the severity of illness (depression). The clinician rates the subject's change based on a bipolar scale from 1(minimum; Very much improved) to 7(maximum; Very much worse). A lower score indicates lower levels of depression as compared to baseline, a higher score indicates higher levels of depression as compared to baseline. A score of 4 (Unchanged) indicates no change in illness compared to baseline. The scale is not calculated as a statistical change score; the clinician rates their impression of change overall. | 12 Weeks | 
| CGI-C Percent Responders (mITT w/LOCF Population) | A summary of the CGI-C percent responders at Week 12 (EOS), by treatment assigned, is shown for the mITT population with LOCF. CGI-C responders were defined as a score of 1 or 2 at the end of the study. A non-responder was defined as a score of ≥3 at end of study. Maximum score is 100%. | 12 Weeks | 
| CDRS-R Total Score (Parent/Other) Week 12 (mITT w/LOCF Population) | A summary of a secondary efficacy outcome measure, Children's Depression Rating Scale (CDRS-R) Total Score (Scored by Parent/Other), at Week 12 (EOS), by treatment assigned, is shown for the modified intent-to-treat (mITT) population, with the last observation carried forward (LOCF) in time. CDRS-R (Parent/Other) total raw scores range from 14 (minimum) 94 (maximum). A lower score indicates a lower likelihood of a depressive disorder, a higher score indicates a higher likelihood of a depressive disorder. One subscale is summed to calculate a total score: Evaluated Symptom Area. Ratings of Observed Nonverbal Behavior subscale is not included in Parent/Other total calculation. | Baseline and 12 Weeks | 
| CDRS-R Total Score (Best Description) Week 12 (mITT w/LOCF Population) | A summary of a secondary efficacy outcome measure, Children's Depression Rating Scale (CDRS-R) Total Score (Best Description), at Week 12 (EOS), by treatment assigned, is shown for the modified intent-to-treat (mITT) population, with the last observation carried forward (LOCF) in time. Best Description ratings are used when ratings based on interviews with different sources (e.g., child, parent, other ratings) differ for a particular symptom. The evaluator must determine which of these ratings most accurately represents the current affective functioning of the child, and circle that rating in the Best Description of Child Column. CDRS-R (Best Description)total raw scores range from 17(minimum) 113(maximum). A lower score indicates a lower likelihood of a depressive disorder, a higher score indicates a higher likelihood of a depressive disorder. Two subscales are summed to calculate a total score: Evaluated Symptom Area and Ratings of Observed Nonverbal Behavior. | 12 Weeks | 
| CDRS-R Total Score (Child) Week 12 (mITT w/OC Population) | A summary of the secondary efficacy outcome measure, Children's Depression Rating Scale (CDRS-R) Total Score (Scored by Child), at Week 12 (EOS), by treatment assigned, is shown for the modified intent-to-treat (mITT) population with observed cases (w/OC). CDRS-R (Child) total raw scores range from 17(minimum) 113(maximum). A lower score indicates a lower likelihood of a depressive disorder, a higher score indicates a higher likelihood of a depressive disorder. Two subscales are summed to calculate a total score: Evaluated Symptom Area and Ratings of Observed Nonverbal Behavior. | 12 Weeks | 
| CDRS-R Total Score (Parent/Other) Week 12 (mITT w/OC Population) | A summary of a secondary efficacy outcome measure, Children's Depression Rating Scale (CDRS-R) Total Score (Scored by Parent/Other), at Week 12 (EOS), by treatment assigned, is shown for the modified intent-to-treat (mITT) population with observed cases (w/OC). CDRS-R (Parent/Other) total raw scores range from 14 (minimum) 94 (maximum). A lower score indicates a lower likelihood of a depressive disorder, a higher score indicates a higher likelihood of a depressive disorder. One subscale is summed to calculate a total score: Evaluated Symptom Area. Ratings of Observed Nonverbal Behavior subscale is not included in Parent/Other total calculation. | 12 Weeks | 
| CDRS-R Total Score (Best Description) Week 12 (mITT w/OC Population) | A summary of a secondary efficacy outcome measure, Children's Depression Rating Scale (CDRS-R) Total Score (Best Description), at Week 12 (EOS), by treatment assigned, is shown for the modified intent-to-treat (mITT) population, with observed cases (w/OC). Best Description ratings are used when ratings based on interviews with different sources (e.g., child, parent, other ratings) differ for a particular symptom area. The evaluator must determine which of these ratings most accurately represents the current affective functioning of the child, and circle that rating in the Best Description of Child Column. CDRS-R (Best Description) total raw scores range from 17(minimum) 113(maximum). A lower score indicates a lower likelihood of a depressive disorder, a higher score indicates a higher likelihood of a depressive disorder. Two subscales are summed to calculate a total score: Evaluated Symptom Area and Ratings of Observed Nonverbal Behavior. | 12 Weeks | 
| Physical Examination (Screening vs. EOS) | Number of physical examination findings that were normal at screening, but abnormal at end of study are presented. Four subjects receiving placebo and four subjects receiving EMSAM had abnormal findings on physical examination at the end of study that were normal at screening. | 12 Weeks | 
| Urinalysis (Change From Baseline) | A summary of a secondary safety outcome measure, Urinalysis (Change from Baseline), by treatment assigned, is shown for the safety population. Mean changes from baseline are provided for PH and specific gravity. | 12 Weeks | 
| Vital Signs-Heart Rate (Change From Baseline) | Summary mean change in heart rate measured in beats per minute (beats/min or BPM) (supine, standing, and orthostatic change)results for all subjects are presented. | 12 Weeks | 
| Vital Signs-Blood Pressure (Change From Baseline) | Summary mean change in blood pressure (systolic/diastolic) measured in millimeters of mercury (mmHg) (supine, standing, and orthostatic change)results for all subjects are presented. | 12 Weeks | 
| 12 Lead ECG (Change From Baseline) | A summary of a secondary safety outcome measure, 12 Lead electrocardiogram (ECG) (Change from Baseline) measured in milliseconds (msec), by treatment assigned, is shown for the safety population. Mean change from Baseline in PR interval, QRS duration, QT interval, and QTc (Bazett and Fridericia corrections) interval are presented. | 12 Weeks | 
| 12 Lead ECG (Change From Baseline)Ventricular Heart Rate | A summary of a secondary safety outcome measure, 12 Lead electrocardiogram (ECG) (Change from Baseline)Ventricular Heart Rate measured in beats per minute(beats/min or BPM), by treatment assigned, is shown for the safety population. Mean change from baseline is presented. | 12 Weeks | 
| Hematology - White Blood Cell (WBC) (Change From Baseline) | A summary of a secondary safety outcome measure, Hematology (Change from Baseline), by treatment assigned, is shown for the safety population. Mean change from Baseline in ABS BASOPHILS (X10^9/L), ABS EOSINOPHILS (X10^9/L), ABS LYMPHOCYTES (X10^9/L), ABS MONOCYTES (X10^9/L), and ABS NEUTROPHILS (X10^9/L) are presented. | 12 Weeks | 
| Hematology - Hematocrit (Change From Baseline) | A summary of a secondary safety outcome measure, Hematology - Hematocrit(HCT)(Change from Baseline), by treatment assigned, is shown for the safety population. | 12 Weeks | 
| Hematology - Hemoglobin (Change From Baseline) | A summary of a secondary safety outcome measure, Hematology - Hemoglobin(HGB)(Change from Baseline), by treatment assigned, is shown for the safety population. | 12 Weeks | 
| Hematology - Red Blood Cell (Change From Baseline) | A summary of a secondary safety outcome measure, Hematology - Red Blood Cell (RBC)(Change from Baseline), by treatment assigned, is shown for the safety population. | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mental Health, Adolescents, Major Depressive Disorder, Depression, Adolescent Depression, Pediatric Depression