A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - FORWARD-5 Study

A Phase 3 Efficacy and Safety Study of ALKS 5461 for the Adjunctive Treatment of Major Depressive Disorder (the FORWARD-5 Study)

This study will evaluate the efficacy and safety of ALKS 5461.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Gatineau, Canada, J8T 8J1
    • Alkermes Investigational Site
  • Halifax, Canada, B3S 1M7
    • Alkermes Investigational Site
  • Penticton, Canada, V2A 4M4
    • Alkermes Investigational Site
  • Quebec, Canada, G3K 2P8
    • Alkermes Investigational Site
• Germany
  • Berlin, Germany, 10245
    • Alkermes Investigational Site
  • Berlin, Germany, 10629
    • Alkermes Investigational Site
  • Hannover, Germany, 30159
    • Alkermes Investigational Site
  • Oranienburg, Germany, 16515
    • Alkermes Investigational Site
  • Schwerin, Germany, 19053
    • Alkermes Investigational Site
  • Stralsund, Germany, 18439
    • Alkermes Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Alkermes Investigational Site
  • San Juan, Puerto Rico, 00926
    • Alkermes Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alkermes Investigational Site
  • California
    • Colton, California, United States, 92324
      • Alkermes Investigational Site
    • Garden Grove, California, United States, 92845
      • Alkermes Investigational Site
    • Los Angeles, California, United States, 90024
      • Alkermes Investigational Site
    • Oakland, California, United States, 94612
      • Alkermes Investigational Site
    • Oceanside, California, United States, 92056
      • Alkermes Investigational Site
    • Pico Rivera, California, United States, 90660
      • Alkermes Investigational Site
    • San Gabriel, California, United States, 91776
      • Alkermes Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Alkermes Investigational Site
  • Florida
    • Bradenton, Florida, United States, 34201
      • Alkermes Investigational Site
    • Fort Myers, Florida, United States, 33912
      • Alkermes Investigational Site
    • Melbourne, Florida, United States, 32901
      • Alkermes Investigational Site
    • North Miami, Florida, United States, 33161
      • Alkermes Investigational Site
    • Oakland Park, Florida, United States, 33334
      • Alkermes Investigational Site
    • Winter Haven, Florida, United States, 33880
      • Alkermes Investigational Site
  • Georgia
    • Smyrna, Georgia, United States, 30080
      • Alkermes Investigational Site
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Alkermes Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Alkermes Investigational Site
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • Alkermes Investigational Site
    • Saint Louis, Missouri, United States, 63141
      • Alkermes Investigational Site
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Alkermes Investigational Site
  • New York
    • New York, New York, United States, 10168
      • Alkermes Investigational Site
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • Alkermes Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Alkermes Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97214
      • Alkermes Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Alkermes Investigational Site
  • Texas
    • DeSoto, Texas, United States, 75115
      • Alkermes Investigational Site
    • Wichita Falls, Texas, United States, 76309
      • Alkermes Investigational Site
  • Utah
    • Clinton, Utah, United States, 84015
      • Alkermes Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • Alkermes Investigational Site
    • Seattle, Washington, United States, 98104
      • Alkermes Investigational Site
    • Spokane, Washington, United States, 99204
      • Alkermes Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a 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 an 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 their 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
Experimental: High Dose	Drug: ALKS 5461; Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
Experimental: Low Dose	Drug: ALKS 5461; Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery Asberg Depression Rating Scale (MADRS)-6 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)	The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).	Baseline and 5 weeks (Stage 1) and baseline and 6 weeks (Stage 2), combined together for the overall estimate of treatment effect
Change in MADRS-10 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)	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.	5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
Change From Baseline to End of Treatment in the MADRS-10	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.	5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)

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 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.	5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
Remission Rate	The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤10 at the end of the efficacy period.	5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
Number of Subjects With Adverse Events (AEs)		5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)

Collaborators and Investigators

• Sponsor: Alkermes, Inc.
• Investigators: Study Director: Sanjeev Pathak, MD, Alkermes, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: August 14, 2014
• First Submitted That Met QC Criteria: August 14, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: depression; Alkermes; ALKS 5461; Major depressive disorder (MDD); samidorphan
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major
• Other Study ID Numbers: ALK5461-207