Major Depressive DisorderPhase 3NCT02158533

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

A Phase 3 study testing High Dose ALKS 5461 and Low Dose ALKS 5461 in people with Major Depressive Disorder, run by Alkermes, Inc. at 49 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This study will evaluate the efficacy and safety of ALKS 5461. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Major Depressive Disorder
What is being tested?: High Dose ALKS 5461 and Low Dose ALKS 5461
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 385 participants
Where: 49 sitesin 3 countries
Study dates: May 2014to Dec 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 9Show fewer

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

Trial locations and contacts

49 sites in 3 countries.

Country

City, postcode or hospital

49 sites in 3 countries

United States42 sites

Alkermes Investigational Site
Allentown, Pennsylvania, 18104
Alkermes, Investigational Site
Alpharetta, Georgia, 30005
Alkermes Investigational Site
Austin, Texas, 78731
Alkermes Investigational Site
Baltimore, Maryland, 21208
Alkermes Investigational Site
Baltimore, Maryland, 21285
Alkermes Investigational Site
Berlin, New Jersey, 08009
Alkermes Investigational Site
Birmingham, Alabama, 35226
Alkermes Investigational Site
Brooklyn, New York, 11241
Alkermes Investigational Site
Canton, Ohio, 44718
Alkermes Investigational Site
Carson, California, 90746
Alkermes Investigational Site
Chicago, Illinois, 60640
Alkermes Investigational Site
Coral Springs, Florida, 33067
Alkermes Investigational Site
Dayton, Ohio, 45417
Alkermes Investigational Site
Decatur, Georgia, 30030
Alkermes Investigational Site
Gainesville, Florida, 32607
Alkermes Investigational Site
Hartford, Connecticut, 06106
Alkermes Investigational Site
Houston, Texas, 77081
Alkermes Investigational Site
Joliet, Illinois, 60435
Alkermes Investigational Site
Lauderhill, Florida, 33319
Alkermes Investigational Site
Lincoln, Rhode Island, 02865
Alkermes Investigational Site
Media, Pennsylvania, 19063
Alkermes Investigational Site
Middleton, Wisconsin, 53562
Alkermes Investigational Site
Mount Kisco, New York, 10549
Alkermes Investigational Site
National City, California, 91950
Alkermes Investigational Site
New York, New York, 10128
Alkermes Investigational Site
Newburgh, Indiana, 47630
Alkermes Investigational Site
Norwich, Connecticut, 06360
Alkermes Investigational Site
Oklahoma City, Oklahoma, 73103
Alkermes Investigational Site
Oklahoma City, Oklahoma, 73112
Alkermes Investigational Site
Orange, California, 92868
Alkermes Investigational Site
Orlando, Florida, 32801
Alkermes Investigational Site
Owensboro, Kentucky, 42301
Alkermes Investigational Site
Philadelphia, Pennsylvania, 19107
Alkermes Investigational Site
San Antonio, Texas, 78229
Alkermes Investigational Site
Sherman Oaks, California, 91403
Alkermes Investigational Site
Skokie, Illinois, 60076
Alkermes Investigational Site
Staten Island, New York, 10305
Alkermes Investigational Site
Torrance, California, 90502
Alkermes Investigational Site
Tucson, Arizona, 85712
Alkermes Investigational Site
Upland, California, 91786
Alkermes Investigational Site
Valparaiso, Indiana, 46383
Alkermes Investigational Site
Woodstock, Vermont, 05091

Other trials in United States

Australia4 sites

Alkermes Investigational Site
Brisbane, Queensland, 4000
Alkermes Investigational Site
Frankston, Victoria, 3199
Alkermes Investigational Site
Melbourne, Victoria, 3004
Alkermes Investigational Site
Towong, Queensland, 4066

Other trials in Australia

Canada3 sites

Alkermes Investigational Site
Gatineau, Quebec
Alkermes Investigational Site
Penticton, British Columbia
Alkermes Investigational Site
Québec

Other trials in Canada

About this study

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

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

Conditions: Major Depressive Disorder
Being tested: High Dose ALKS 5461, Low Dose ALKS 5461, Placebo
Keywords: Major Depressive Disorder, Depression, Alkermes, ALKS 5461, Samidorphan
Medical subject headings: Depressive Disorder, Major, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

High Dose ALKS 5461Drug
Also called ALKS 5461
Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
Low Dose ALKS 5461Drug
Also called ALKS 5461
Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
PlaceboDrug
Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)

Study groups in NCT02158533
Study group	Role	What they receive
High Dose	Experimental	Not described Receives: Drug: High Dose ALKS 5461
Low Dose	Experimental	Not described Receives: Drug: Low Dose ALKS 5461
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and 5 weeks for each stage

Secondary outcomes (3)

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).
Measured: 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.
Measured: Baseline and 5 weeks for each stage
Number of Subjects With Adverse Events (AEs)
Measured: 5 weeks for Stage 1 and 6 weeks for Stage 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2014Dec 2015

First posted9 Jun 2014 (estimated)
Study startMay 2014
Primary completionDec 2015
Study completionDec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 385 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02158533
Sponsor's protocol ID: ALK5461-205
Status last verified: Aug 2019
First submitted: 5 Jun 2014
Last updated: 14 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3 Efficacy and Safety Study of ALKS 5461 for the Adjunctive Treatment of Major Depressive Disorder (the FORWARD-4 Study)
ClinicalTrials.gov ID: NCT02158533
Acronym / sponsor ID: ALK5461-205
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder, Depression, Alkermes, ALKS 5461, Samidorphan
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 385 participants (actual)
Lead sponsor: Alkermes, Inc.Industry (pharma, biotech, devices)
Study start: May 2014
Primary completion: Dec 2015 (actual)
Study completion: Dec 2015 (actual)
First posted: 9 Jun 2014 (estimated)
Results: Posted 27 Mar 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
High Dose	Experimental	Drug: High Dose ALKS 5461
Low Dose	Experimental	Drug: Low Dose ALKS 5461
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
High Dose ALKS 5461Also: ALKS 5461Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)	Drug	High Dose
Low Dose ALKS 5461Also: ALKS 5461Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)	Drug	Low Dose
PlaceboSublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)	Drug	Placebo

Primary outcome

Change From Baseline to Week 5 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline and 5 weeks for each stage
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.

3 secondary outcomes

Proportion of Patients Who Exhibited Treatment Response (MADRS-10)
Time frame: Baseline and 5 weeks for each stage
Remission Rate
Time frame: Baseline and 5 weeks for each stage
Number of Subjects With Adverse Events (AEs)
Time frame: 5 weeks for Stage 1 and 6 weeks for Stage 2

Results and safety

Results posted to the registry on 27 Mar 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo S1	265	251
ALKS 5461 0.5mg/0.5mg S1	59	51
ALKS 5461 2mg/2mg S1	60	52
Placebo S2	0	0
ALKS 5461 0.5mg/0.5mg S2	0	0
ALKS 5461 2mg/2mg S2	0	0

Primary outcome: Change From Baseline to Week 5 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score

Time frame: Baseline and 5 weeks for each stage. Least squares mean (Standard Error). Unit: units on a scale

Measure	Placebo S1 n = 256	ALKS 5461 0.5mg/0.5mg S1 n = 58	ALKS 5461 2mg/2mg S1 n = 59	Placebo S2 n = 54	ALKS 5461 0.5mg/0.5mg S2 n = 55	ALKS 5461 2mg/2mg S2 n = 54
Value	-11.1 (0.67)	-8.4 (1.49)	-13.0 (1.50)	-2.2 (1.08)	-4.8 (1.27)	-3.9 (1.13)

Placebo S1 vs ALKS 5461 2mg/2mg S1 vs Placebo S2 vs ALKS 5461 2mg/2mg S2: Least squares mean difference: -1.8 (95% CI -4.1 to 0.4), p = 0.109, Mixed Models Analysis
Placebo S1 vs ALKS 5461 0.5mg/0.5mg S1 vs Placebo S2 vs ALKS 5461 0.5mg/0.5mg S2: Least squares mean difference: 0.0 (95% CI -2.3 to 2.3), p = 0.975, Mixed Models Analysis

Population analysed: Stage 1 and Stage 2 Full Analysis Sets (FAS) consisted of subjects who were randomized and took at least 1 dose of study drug and had at least 1 postbaseline MADRS-10 assessment in the respective stage.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 5 weeks for Stage 1 and 6 weeks for Stage 2. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo S1	1 of 265 (0.4%)	81 of 265 (30.6%)	0 of 265
ALKS 5461 0.5mg/0.5mg S1	0 of 59 (0%)	32 of 59 (54.2%)	0 of 59
ALKS 5461 2mg/2mg S1	0 of 60 (0%)	36 of 60 (60%)	0 of 60
Placebo S2	0 of 56 (0%)	11 of 56 (19.6%)	0 of 56
ALKS 5461 0.5mg/0.5mg S2	0 of 56 (0%)	13 of 56 (23.2%)	0 of 56
ALKS 5461 2mg/2mg S2	0 of 56 (0%)	22 of 56 (39.3%)	0 of 56

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Major Depressive Disorder

Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sanjeev Pathak, MD study director

Alkermes, Inc.

49 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing High Dose ALKS 5461 and Low Dose ALKS 5461 in people with Major Depressive Disorder, run by Alkermes, Inc. at 49 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 5 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score (time frame: Baseline and 5 weeks for each stage). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02158533.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2019.