Major Depressive DisorderPhase 3NCT02158546

A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-3 Study

A Phase 3 study testing ALKS 5461 in people with Major Depressive Disorder, run by Alkermes, Inc. at 58 sites in 2 countries.

Completed

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

Official record

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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?: ALKS 5461
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 447 participants
Where: 58 sitesin 2 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

58 sites in 2 countries.

Country

City, postcode or hospital

58 sites in 2 countries

United States50 sites

Alkermes Investigational Site
Albuquerque, New Mexico, 87109
Alkermes Investigational Site
Atlanta, Georgia, 30331
Alkermes Investigational Site
Beachwood, Ohio, 44122
Alkermes Investigational Site
Bellevue, Washington, 98007
Alkermes Investigational Site
Bellflower, California, 90706
Alkermes Investigational Site
Beverly Hills, California, 90210
Alkermes Investigational Site
Brockton, Massachusetts, 02301
Alkermes Investigational Site
Charleston, South Carolina, 29407
Alkermes Investigational Site
Charlotte, North Carolina, 28204
Alkermes Investigational Site
Cherry Hill, New Jersey, 08002
Alkermes Investigational Site
Chicago, Illinois, 60634
Alkermes Investigational Site
Cincinnati, Ohio, 45215
Alkermes Investigational Site
Cincinnati, Ohio, 45227
Alkermes Investigational Site
Dallas, Texas, 75231
Alkermes Investigational Site
Dallas, Texas, 75309
Alkermes Investigational Site
Edgewood, Kentucky, 41017
Alkermes Investigational Site
Glendale, California, 91206
Alkermes Investigational Site
Hallandale, Florida, 33009
Alkermes Investigational Site
Hialeah, Florida, 33016
Alkermes Investigational Site
Houston, Texas, 77098
Alkermes Investigational Site
Indianapolis, Indiana, 46260
Alkermes Investigational Site
Jacksonville, Florida, 32256
Alkermes Investigational Site
Jamaica, New York, 11432
Alkermes Investigational Site
Kansas City, Missouri, 64114
Alkermes Investigational Site
Lafayette, Indiana, 47905
Alkermes Investigational Site
Leesburg, Florida, 34748
Alkermes Investigational Site
Little Rock, Arkansas, 72211
Alkermes Investigational Site
Los Alamitos, California, 90720
Alkermes Investigational Site
Maitland, Florida, 32751
Alkermes Investigational Site
Mason, Ohio, 45040
Alkermes Investigational Site
Memphis, Tennessee, 38119
Alkermes Investigational Site
Middleburg Heights, Ohio, 44130
Alkermes Investigational Site
New York, New York, 10023
Alkermes Investigational Site
O'Fallon, Missouri, 63368
Alkermes Investigational Site
Oak Brook, Illinois, 60523
Alkermes Investigational Site
Orange, California, 92868
Alkermes Investigational Site
Philadelphia, Pennsylvania, 19104
Alkermes Investigational Site
Portland, Oregon, 97210
Alkermes Investigational Site
Redlands, California, 92374
Alkermes Investigational Site
Salem, Oregon, 97301
Alkermes Investigational Site
St Louis, Missouri, 63109
Alkermes Investigational Site
Staten Island, New York, 10312
Alkermes Investigational Site
Sugar Land, Texas, 77478
Alkermes Investigational Site
Tampa, Florida, 33613
Alkermes Investigational Site
Temecula, California, 92591
Alkermes Investigational Site
Vernon Hills, Illinois, 60061
Alkermes Investigational Site
Washington D.C., District of Columbia, 20016
Alkermes Investigational
Washington DC, Maryland, 20016
Alkermes Investigational Site
Watertown, Massachusetts, 02472
Alkermes Investigational Site
Waukesha, Wisconsin, 53188

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Bulgaria8 sites

Alkermes Investigational Site
Burgas, 8001
Alkermes Investigational Site
Kazanlak, 6100
Alkermes Investigational Site
Sofia, 1113
Alkermes Investigational Site
Sofia, 1431
Alkermes Investigational Site
Sofia, 1632
Alkermes Investigational Site
Varna, 9020
Alkermes Investigational Site
Veliko Tarnovo, 5000
Alkermes Investigational Site
Vratsa, 3000

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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-3 Study)

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

Conditions: Major Depressive Disorder
Being tested: 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.

ALKS 5461Drug
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 NCT02158546
Study group	Role	What they receive
ALKS 5461	Experimental	Not described Receives: Drug: 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 End of Treatment (Week 6) 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 week 6

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 6).
Measured: 6 weeks
Remission Rate
The proportion of subjects achieving remission, defined as a MADRS-10 score of ≤ 10 at the end of the efficacy period.
Measured: 6 weeks
Number of Subjects With Adverse Events (AEs)
Measured: 6 weeks

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: 447 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02158546
Sponsor's protocol ID: ALK5461-206
Status last verified: May 2019
First submitted: 5 Jun 2014
Last updated: 25 Jun 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

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Study at a glance

From the registry record, last updated by the sponsor on 25 Jun 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-3 Study)
ClinicalTrials.gov ID: NCT02158546
Acronym / sponsor ID: ALK5461-206
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder, Depression, Alkermes, ALKS 5461, Samidorphan
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 447 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 25 Jun 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: 2

Arm	Type	Receives
ALKS 5461	Experimental	Drug: 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
ALKS 5461Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)	Drug	ALKS 5461
PlaceboSublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)	Drug	Placebo

Primary outcome

Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline and week 6
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: 6 weeks
Remission Rate
Time frame: 6 weeks
Number of Subjects With Adverse Events (AEs)
Time frame: 6 weeks

Results and safety

Results posted to the registry on 25 Jun 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
Group 1 - ALKS 5461 2mg/2mg	152	133
Group 1 - Placebo	153	136
Group 2 ALKS 5461 2mg/2mg	18	14
Group 2 - Placebo	19	13

Primary outcome: Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score

Time frame: Baseline and week 6. Least squares mean (Standard Error). Unit: units on a scale

Measure	ALKS 5461 2mg/2mg n = 142	Placebo n = 146
Value	-4.8 (0.67)	-4.6 (0.66)

ALKS 5461 2mg/2mg vs Placebo: Least square means difference: -0.3 (95% CI -2.1 to 1.6), p = 0.782, Mixed Models Analysis

Population analysed: The Full Analysis Set (FAS) consists of subjects in the Group 1 Safety Population who have at least 1 post-randomization assessment of MADRS total score.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: AE reporting includes the 6-week double-blind, placebo-controlled period.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1 ALKS 5461 2mg/2mg	0 of 147 (0%)	39 of 147 (26.5%)	0 of 147
Group 1 Placebo	1 of 148 (0.7%)	24 of 148 (16.2%)	0 of 148
Group 2 ALKS 5461 2mg/2mg	0 of 15 (0%)	11 of 15 (73.3%)	0 of 15
Group 2 Placebo	0 of 15 (0%)	8 of 15 (53.3%)	0 of 15

Limitations and caveats (from the sponsor): Pre-specified primary population data are shown. Data from one trial site were excluded as pre-specified due to data integrity concerns (18 subjects). Other excluded subjects did not receive randomized study drug.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Major Depressive Disorder

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Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
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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.

58 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ALKS 5461 in people with Major Depressive Disorder, run by Alkermes, Inc. at 58 sites in 2 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 25 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States, Bulgaria. 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 25 Jun 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 End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score (time frame: Baseline and week 6). 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 NCT02158546.

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 25 Jun 2019.