A Study of ALKS 5461 for Treatment Refractory Major Depressive Disorder (MDD)

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety, and tolerability of adjunctive ALKS 5461 in adults who have treatment refractory MDD.

Official Title
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A Phase 3b Efficacy and Safety Study of Adjunctive ALKS 5461 in Treatment Refractory Major Depressive Disorder

Conditions
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Major Depressive Disorder

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a Major Depressive Disorder (MDD) primary diagnosis Have a body mass index (BMI) of 18.0 to </= 40.0 kg/m^2 Be willing and able to follow the study procedures and visits as outlined in the protocol (including agreeing not to enroll in any other clinical trials) Have inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE) Additional criteria may apply Exclusion Criteria: Has any finding that would compromise the safety of the subject or affect their ability to adhere to the protocol visit schedule or fulfill visit requirements Has any other significant medical condition (eg, neurological, psychiatric, or metabolic) or clinical symptom that could unduly risk the subject or affect the interpretation of study data Has any current primary diagnosis other than MDD, where primary diagnosis is defined as the primary source of current distress and functional impairment Has experienced hallucinations, delusions, or any psychotic symptoms in the current MDE Has been hospitalized for MDD within 3 months before screening Has used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid antagonists (eg, naloxone, naltrexone) within 14 days prior to screening Has received electroconvulsive therapy treatment within the last 2 years or within the current MDE or failed a course of electroconvulsive treatment at any time Has a significant risk for suicide Has a positive breath alcohol test at screening Has a positive test for drugs of abuse at screening or visit 2 Is pregnant, planning to become pregnant, or is breastfeeding during the study 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: ALKS 5461<br>Sublingual tablets | Drug: ALKS 5461<br>* Samidorphan + buprenorphine, administered sublingually<br>|
| Placebo Comparator: ALKS 5461 Placebo<br>Sublingual tablets | Drug: ALKS 5461 Placebo<br>* Placebo tablet, administered sublingually<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the End of Treatment (EOT) in the Montgomery Asberg Depression Rating Scale-10 (MADRS-10) Scores | The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of Major Depressive Disorder (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 Stage 1, Baseline and 6 weeks for Stage 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery Asberg Depression Rating Scale (MADRS) Response Rate | The percentage of subjects demonstrating a MADRS-10 treatment response, defined as a >/= 50% reduction in MADRS-10 score from baseline to the end of the efficacy period (Week 5 for Stage 1, Week 6 for Stage 2). The MADRS-10 scale is a measure of the severity of Major Depressive Disorder (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 Stage 1, Baseline and 6 weeks for Stage 2 | 
| Montgomery Asberg Depression Rating Scale (MADRS) Remission Rate | The percentage of subjects achieving remission, defined as a subject with a score </= 10 at the end of the efficacy period (Week 5 for Stage 1, Week 6 for Stage 2). The MADRS-10 scale is a measure of the severity of Major Depressive Disorder (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).the end of the efficacy period. | 5 weeks for Stage 1, 6 weeks for Stage 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alkermes, Major Depressive Disorder, Treatment Refractory MDD, ALKS 5461