SPD489 in Adults With Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder

Study Overview
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Brief Summary
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To evaluate the efficacy of SPD489 for the treatment of executive function impairments (EFI) when used as an adjunct to stable, standard therapy in the setting of partial or full remission from recurrent Major Depressive Disorder (MDD) as measured by the Global Executive Composite (GEC) T-score of the Behavioral Rating Inventory of Executive Functioning - Adult Version (BRIEF-A).

Official Title
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Phase 2, Multicenter, Randomized, Double-blind, Placebo-Controlled, Study to Evaluate the Efficacy, Safety, and Tolerability of SPD489 in Adults With Clinically Significant, Persistent Executive Function Impairments (EFI) and Partial or Full Remission of Recurrent Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: SPD489 (Lisdexamfetamine dimesylate)
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18-55 with a primary diagnosis of nonpsychotic uni-polar depression Exclusion Criteria: Current co-morbid psychiatric disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Active<br>SPD489 | Drug: SPD489 (Lisdexamfetamine dimesylate)<br>* Oral, 20, 30, 40, 50, 60, and 70mg capsules, once daily<br>* Other names: Vyvanse;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Matching placebo<br>* oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Behavior Rating Inventory of Executive Function - Adult Version Global Executive Composite T-score (BRIEF-A GEC T) at Week 9, Last Observation Carried Forward (LOCF) | BRIEF-A Global Executive Composite assesses behavioral aspects of executive function. Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. | Baseline and week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Montgomery-Ǻsberg Depression Rating Scale (MADRS) Total Score at Week 9 - (LOCF) | MADRS is a validated, 10-item rating scale with each item being scored on a scale from 0-6 with a total score ranging from 0-60. Lower scores indicate a decreased severity of depression. | Baseline and week 9 | 
| Change From Baseline in BRIEF-A T-scores at Week 9, LOCF | BRIEF-A is a validated 75-item questionnaire. Items are rated 1 (never), 2 (sometimes), and 3 (often). There is no range for a total score. Raw scale scores are used to generate T-scores. A reduction in score indicates less impairment. | Baseline and week 9 | 
| Change From Baseline in Central Nervous System Vital Signs Computerized Cognitive Testing Battery Neurocognitive Domain and Index Scores at up to 9 Weeks/Endpoint | This measures the speed and accuracy of basic mental functions. Scores are normalized from raw scores and present an age matched score relative to other people in a normative sample. Scores are normalized with a mean of 100 and standard deviation of 15. Scores < 70 indicate likely deficit and impairment, and scores > 110 indicate high function and capacity. Higher scores are better. | Baseline and up to 9 weeks/Endpoint | 
| Percent of Participants With Clinical Global Impression - Severity of Illness (CGI-S) at Baseline | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) | Baseline | 
| Percent of Participants With CGI-S at up to 9 Weeks/Endpoint | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) | Up to 9 weeks/Endpoint | 
| Percentage of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) at Week 9, LOCF | Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale. | Week 9 | 
| Change From Baseline in Endicott Work Productivity Scale (EWPS) Total Score at up to 9 Weeks/Endpoint | The EWPS quantifies work performance, productivity attitudes and behaviors assessing 25 items on a scale ranging from 0 (high performance) to 4 (lowest performance). Scores range from 0 to 100 with 100 representing lowest productivity. | Baseline and up to 9 weeks/Endpoint | 
| Change From Baseline in Changes in Sexual Functioning Questionnaire (CSFQ-14) Total Scores for Males at Week 9, LOCF | This is a 14 item self-report tool that evaluates sexual functioning. Each item is scored on a 5-point Likert scale ranging from 1 (never) to 5 (always) with total scores ranging from 14 to 70. Higher scores reflect better sexual functioning. | Baseline and week 9 | 
| Change From Baseline in CSFQ-14 Total Scores for Females at Week 9, LOCF | This is a 14 item self-report tool that evaluates sexual functioning. Each item is scored on a 5-point Likert scale ranging from 1 (never) to 5 (always) with total scores ranging from 14 to 70. Higher scores reflect better sexual functioning. | Baseline and week 9 | 
| Change From Baseline in Short Form-12 Health Survey (SF-12) Scale Total Scores at Week 9 | The SF-12 is a 12-item self-report questionnaire that is a subset of the SF-36 Health Survey. The survey captures physical and mental health. Each of the 12 items is scored using various scales with a total score ranging from 0 (lowest level of health) to 100 (highest level of health). | Baseline and week 9 | 
| Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Total Scores at up to 9 Weeks/Endpoint | The Q-LES-Q is a 93-item self-report questionnaire on quality of life and health. Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good) with a total score ranging from 93 to 465. Higher scores indicate greater satisfaction. | Baseline and up to 9 weeks/Endpoint | 
| Change From Baseline in Amphetamine Cessation Symptom Assessment (ACSA) Total Score at Week 11 | ACSA scale has 16 symptom items rated on a scale from 0 (not at all) to 4 (extremely) with a possible total score range of 0 to 64. Higher scores indicate greater withdrawal symptom severity. | Baseline and week 11 | 
| Change From Baseline in the Generalized Anxiety Disorder 7-Item (GAD-7) Total Score at Week 9, LOCF | The GAD-7 is a 7-item self-report questionnaire for assessing anxiety severity. Each item is scored using a scale that ranges from 0 (not at all) to 3 (nearly every day) with total scores ranging from 0 to 21. Lower scores indicate a reduction in anxiety. | Baseline and week 9 | 
| Change From Baseline in Sheehan Suicidality Tracking Scale (STS) Total Score at Week 9 | The STS is an 8-question clinician-rated assessment of suicidal ideation, suicidal behavior, and accidents. The items are scored on a 5-point Likert scale from 0 (not at all) to 4 (extremely) and summed to produce a total score ranging from 0 to 32. Lower scores indicate reduced suicidal tendencies. | Baseline and week 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder