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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: ALKS 5461; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Alkermes Investigational Site
  • California
    • Oceanside, California, United States, 92056
      • Alkermes Investigational Site
    • Santa Ana, California, United States, 92701
      • Alkermes Investigational Site
    • Torrance, California, United States, 90502
      • Alkermes Investigational Site
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Alkermes Investigational Site
    • Lauderhill, Florida, United States, 33319
      • Alkermes Investigational Site
    • Leesburg, Florida, United States, 34748
      • Alkermes Investigational Site
    • North Miami, Florida, United States, 33161
      • Alkermes Investigational Site
    • Saint Petersburg, Florida, United States, 33716
      • Alkermes Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Alkermes Investigational Site
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Alkermes Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21285
      • Alkermes Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Alkermes Investigational Site
    • Haverhill, Massachusetts, United States, 01830
      • Alkermes Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Alkermes Investigational Site
  • New York
    • Brooklyn, New York, United States, 11241
      • Alkermes Investigational Site
    • New York, New York, United States, 10021
      • Alkermes Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Alkermes Investigational Site
    • Dayton, Ohio, United States, 45417
      • Alkermes Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Alkermes Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Alkermes Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Alkermes Investigational Site
  • Texas
    • Austin, Texas, United States, 78754
      • Alkermes Investigational Site
    • Dallas, Texas, United States, 75235
      • Alkermes Investigational Site
    • Houston, Texas, United States, 77081
      • Alkermes Investigational Site
    • San Antonio, Texas, United States, 78229
      • Alkermes Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • Alkermes Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Two placebo tablets, given daily
Experimental: ALKS 5461	Drug: ALKS 5461; Two active tablets, given daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alkermes, Inc.
• Investigators: Study Director: Richard Leigh-Pemberton, MD, Alkermes, Inc.

Publications and helpful links

General Publications

• Fava M, Memisoglu A, Thase ME, Bodkin JA, Trivedi MH, de Somer M, Du Y, Leigh-Pemberton R, DiPetrillo L, Silverman B, Ehrich E. Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2016 May 1;173(5):499-508. doi: 10.1176/appi.ajp.2015.15070921. Epub 2016 Feb 12.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: December 22, 2011
• First Submitted That Met QC Criteria: December 27, 2011
• First Posted (Estimate): December 28, 2011

Study Record Updates

• Last Update Posted (Actual): May 21, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: ALK5461-202