A Study to Evaluate ALKS 5461 in Subjects With Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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This study will evaluate the efficacy of ALKS 5461 when administered daily for 4 weeks to adults with Major Depressive Disorder (MDD) and inadequate response to antidepressant therapy.

Detailed Description
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The study will measure efficacy using the HAM-D-17, the MADRS, and the CGI-S as well as using other scales and assessments.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate ALKS 5461 in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Therapy

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: ALKS 5461
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with a major depressive episode (MDE) Body mass index less than or equal to 40 kg/m2 Have been treated with an adequate dose of SSRI/SNRI during the current MDE for at least 8 weeks, with the same, adequate dose over the last 4 weeks that is expected to remain stable throughout the study History of inadequate response during the entire current MDE to 1 or 2 adequate antidepressant treatments, including current treatment Be otherwise physically healthy Exclusion Criteria: Have an axis I diagnosis of delirium, dementia, amnestic or other cognitive disorder, schizophrenia or other psychotic disorder, bipolar I or II disorder, eating disorder, obsessive-compulsive disorder, panic disorder, acute stress disorder, or posttraumatic stress disorder Have a clinically significant current axis II diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder Are experiencing hallucinations, delusions, or any psychotic symptomatology in the current MDE Receive new onset psychotherapy within 6 weeks of screening Use of opioid agonists (eg, codeine, oxycodone, morphine) within 14 days before screening Have received electroconvulsive therapy during the current MDE Have attempted suicide within the past 2 years Have a thyroid pathology Have a history of a seizure disorder or of neuroleptic malignant syndrome/serotonin syndrome Have a positive test for human immunodeficiency virus (HIV) Additional inclusion/exclusion criteria may apply

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: ALKS 5461<br> | Drug: ALKS 5461<br>* Two active tablets, given daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Two placebo tablets, given daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 4 in Hamilton Rating Scale for Depression (HAM-D17) Total Score | The HAM-D17 scale is a clinician-administered questionnaire comprised of 17 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 50 (most severe symptoms). Individual questionnaire items include depressed mood, work and activities, insomnia (early), insomnia (middle), insomnia (late), genital symptoms, somatic symptoms (gastrointestinal), loss of weight, somatic symptoms (general), feelings of guilt, suicide, anxiety (psychic), anxiety (somatic), hypochondriasis, insight, agitation, and retardation. | Baseline and 4 weeks for each stage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Exhibited Treatment Response (HAM-D17) | The proportion of subjects demonstrating HAM-D17 treatment response, defined as a ≥ 50% reduction in HAM-D17 score from baseline to the end of the efficacy period (Week 4). The HAM-D17 is a clinician administered questionnaire comprised of 17 questions used to assess the severity of a patient's depression. Scores range from 0 (no apparent symptoms) to 50 (most severe symptoms). Individual questionnaire items include depressed mood, work and activities, insomnia (early), insomnia (middle), insomnia (late), genital symptoms, somatic symptoms (gastrointestinal), loss of weight, somatic symptoms (general), feelings of guilt, suicide, anxiety (psychic), anxiety (somatic), hypochondriasis, insight, agitation, and retardation. | 4 weeks for each stage | 
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts. | 4 weeks for each stage | 
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score | The CGI-S is a 7-point scale that requires the clinician to assess how mentally ill the patient is at a specific point in time. Based on the scale, patients are categorized as follows: 1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; and 7: among the most extremely ill patients. | 4 weeks for each stage |