Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder

Study Overview
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Brief Summary
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This study will examine SPD489 in subjects aged 18-65 with major depressive disorder (MDD) who are taking certain types of antidepressants but continue to have residual depression symptoms. Eligible patients will remain on their antidepressant but will be randomized to either receive supplemental SPD489 or placebo (i.e. sugar pill). The purpose of this study is to help answer the following questions: How safe is SPD489 for the supplemental treatment of depression and what are the side effects that might be related to it? Can supplemental SPD489 help patients who still have residual depression symptoms while taking an antidepressant? How much SPD489 should be given to patients with depression who are also taking an antidepressant? How does SPD489 compare to placebo in depressed patients who are also taking an antidepressant?

Official Title
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The SPD489-322 Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Flexible Dose Titration, Efficacy and Safety Study of SPD489 in Combination With an Antidepressant in the Treatment of Adults With Major Depressive Disorder With Inadequate Response to Prospective Treatment With an Antidepressant

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: SPD489 (Lisdexamfetamine dimesylate )
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is able to provide written, personally signed, and dated informed consent to participate in the study. Subject is between 18 and 65 years of age. Subject has a primary diagnosis of non-psychotic MDD (single or recurrent). Subject has a MADRS total score 24. Subject who is female, must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test and a negative urine pregnancy test at the and agrees to comply with any applicable contraceptive requirements of the protocol. Subject is able to swallow a capsule. Exclusion Criteria: Subject whose current episode of MDD has not responded to an adequate treatment regimen with 2 or more approved single antidepressant agents. Subject who has a lifetime history of treatment resistant depression. Subject has a current co-morbid psychiatric disorder. Excluded are: any significant Axis II disorder (including borderline personality disorder), any bipolar disorder, any current or lifetime psychosis, post traumatic stress disorder, obsessive compulsive disorder, any pervasive development disorder, anorexia nervosa and bulimia nervosa. Subject has been hospitalized (within the last 12 months) for their current MDD episode. Subject has a current or lifetime history of attention-deficit/hyperactivity disorder (ADHD). Subject has a first degree relative that has been diagnosed with bipolar I disorder. Subject has a recent history (within the last 6 months) of suspected substance abuse or dependence disorder Subject is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt within the past 3 years, or is currently demonstrating active suicidal ideation. Subject has a concurrent chronic or acute illness or unstable medical condition. Subject has a history of seizures (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder, serious neurological disease, history of significant head trauma, dementia, cerebrovascular disease, Parkinson's disease, or intracranial lesions. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Subject has a history of thyroid disorder that has not been stabilized on thyroid medication or treatment within 3 months prior to the Screening Visit. Subject has a known family history of sudden cardiac death or ventricular arrhythmia. Subject has glaucoma. Subject has a history of moderate to severe hypertension. Current use of any other medications (including over-the-counter [OTC], herbal or homeopathic preparations) that have central nervous system effects. Subject has had electroconvulsive therapy (ECT) for the current depressive episode 3 months prior. The subject has a known or suspected intolerance, hypersensitivity, or contraindications to their assigned antidepressant treatments (escitalopram oxalate, sertraline HCl, venlafaxine HCl extended release, or duloxetine HCl). Subject has a positive urine drug result. Subject has a body mass index (BMI) of <18.5 or >40. Subject is female and is pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antidepressant + SPD489<br> | Drug: SPD489 (Lisdexamfetamine dimesylate )<br>* Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride) oral, once daily + SPD489 (oral, 20, 30, 50 or 70 mg, once daily) for 8 weeks<br>* Other names: Vyvanse;|
| Placebo Comparator: Antidepressant + Placebo<br> | Drug: Placebo<br>* Antidepressant (either escitalopram oxalate, sertraline hydrochloride, venlafaxine hydrochloride extended release or duloxetine hydrochloride) oral, once daily + Placebo (oral, once daily) for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at up to 8 Weeks | 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score at up to 8 Weeks | Designed to evaluate the extent to which illness symptoms impact a subject's life in 3 areas: work/school, social, and family/home. Each area is scored on a scale from 0 (no impairment) to 10 (highly impaired) with a total score ranging from 0 (unimpaired) to 30 (highly impaired). Lower scores translate into less impairment. | 8 weeks | 
| Percentage of Participants Achieving a 25% Response on the MADRS | The percentage of subjects who achieved a 25% response (i.e., ≥25% reduction in MADRS total score from Lead-in Baseline, Visit 2; Week 0). A comparison was performed at Visit 14/Early Termination (ET) (Week 16/ET). | up to 8 weeks | 
| Percentage of Participants Achieving a 50% Response on the MADRS | The percentage of subjects who achieved a 50% response (i.e., ≥50% reduction in MADRS total score from Lead-in Baseline, Visit 2; Week 0). A comparison was performed at Visit 14/ET (Week 16/ET). | up to 8 weeks | 
| Percentage of Participants Achieving Remission on the MADRS | MADRS remission was defined as a MADRS total score of ≤10. A comparison was performed at Visit 14/ET (Week 16/ET). | up to 8 weeks | 
| Mean Change From Baseline Over Time in MADRS Total Score | 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 up to 8 weeks | 
| Mean Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self Report (QIDS SR) | The QIDS-SR is a self-administered questionnaire designed to rate depressive symptoms. The scale contains 16 items, each scored using a 4-point scale ranging from 0 (representing the most favorable response [low amount of symptom]) to 3 (representing the least favorable response [frequent/intense symptom]). The total score could range from 0 (no depression) to 27 (very severe depression). Higher scores represent more severe depressive symptoms. | up to 8 weeks | 
| Mean Change From Baseline in the Short Form-12 Health Survey V2 (SF-12V2) | Total score ranges from 0 (lowest level of health) - 100 (highest level of health) on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (i.e. a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability). Higher scores are associated with better quality of life. | up to 8 weeks | 
| Mean Change From Baseline in the Quality of Life Enjoyment Satisfaction Questionnaire Short Form (Q-LES-Q-SF) | The short form is a 16-item self-report questionnaire which evaluates general subject satisfaction with health, mood, relationships, functioning in daily life, and the treatment being taken. Overall level of satisfaction is evaluated on a 5-point scale from 1 (very poor) to 5 (very good). The total score ranges from 14-70 (last two items on the form are not included in the total score). A higher score indicates a better quality of life. | up to 8 weeks | 
| Clinical Global Impressions - Global Improvement (CGI-I) | 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. | up to 8 weeks | 
| Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS is a semi-structured interview that captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The interview includes definitions and suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. The assessment is done by the nature of the responses, not by a numbered scale. | up to 8 weeks | 
| Amphetamine Cessation Symptom Assessment (ACSA) | 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. | up to 8 weeks |