A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-4 Study

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of ALKS 5461.

Official Title
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A Phase 3 Efficacy and Safety Study of ALKS 5461 for the Adjunctive Treatment of Major Depressive Disorder (the FORWARD-4 Study)

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: High Dose ALKS 5461
* Drug: Low Dose ALKS 5461
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a Body Mass Index (BMI) of 18.0 to 40.0 kg/m2, inclusive Agree to use an acceptable method of contraception for the duration of the study Have a Major Depressive Disorder (MDD) primary diagnosis Have no more than 2 inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE) Additional criteria may apply Exclusion Criteria: Have a current primary Axis-I disorder other than MDD Have used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid antagonists (eg, naloxone, naltrexone) within 14 days Have received electroconvulsive therapy treatment within the last 2 years or received more than one course of electroconvulsive treatment during lifetime Have attempted suicide within the past 2 years Have a positive test for drugs of abuse Are pregnant, planning to become pregnant, or breastfeeding Have a history of intolerance, allergy, or hypersensitivity to buprenorphine or opioid antagonists (eg, naltrexone, naloxone) Have had a significant blood loss or blood donation within 60 days Additional criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: High Dose<br> | Drug: High Dose ALKS 5461<br>* Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)<br>* Other names: ALKS 5461;|
| Experimental: Low Dose<br> | Drug: Low Dose ALKS 5461<br>* Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)<br>* Other names: ALKS 5461;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 5 in the 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. | Baseline and 5 weeks for each stage | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Exhibited Treatment Response (MADRS-10) | The proportion of subjects demonstrating MADRS-10 treatment response, defined as a >/= 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (Week 5). The MADRS-10 scale is a measure of the severity of MDD symptoms and includes the following 10 items: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). | Baseline and 5 weeks for each stage | 
| Remission Rate | The proportion of subjects achieving remission, defined as a MADRS-10 score of </= 10 at the end of the efficacy period. | Baseline and 5 weeks for each stage | 
| Number of Subjects With Adverse Events (AEs) |  | 5 weeks for Stage 1 and 6 weeks for Stage 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Depression, Alkermes, ALKS 5461, Samidorphan