A Study of ALKS 5461 for the Treatment of Major Depressiv... | NCT02158533 | Trialant
NCT02158533
Sponsor
Alkermes, Inc.
Status
Completed
Last Update Posted
Aug 14, 2019Actual
Enrollment
385Actual
Phase
Phase 3
Conditions
Major Depressive Disorder
Interventions
High Dose ALKS 5461
Low Dose ALKS 5461
Placebo
Countries
United States
Australia
Canada
Protocol Section
Identification Module
NCT ID
NCT02158533
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
ALK5461-205
Secondary IDs
Not provided
Brief Title
A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-4 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)
Acronym
Not provided
Organization
Alkermes, Inc.INDUSTRY
Status Module
Record Verification Date
Aug 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
May 2014
Primary Completion Date
Dec 2015Actual
Completion Date
Dec 2015Actual
First Submitted Date
Jun 5, 2014
First Submission Date that Met QC Criteria
Jun 6, 2014
First Posted Date
Jun 9, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 1, 2019
Results First Submitted that Met QC Criteria
Mar 1, 2019
Results First Posted Date
Mar 27, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Feb 3, 2016
Certification/Extension First Submitted that Passed QC Review
Feb 3, 2016
Certification/Extension First Posted Date
Mar 2, 2016Estimated
Last Update Submitted Date
Aug 2, 2019
Last Update Posted Date
Aug 14, 2019Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Alkermes, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This study will evaluate the efficacy and safety of ALKS 5461.
Detailed Description
Not provided
Conditions Module
Conditions
Major Depressive Disorder
Keywords
Major Depressive Disorder
Depression
Alkermes
ALKS 5461
Samidorphan
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
385Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
High Dose
Experimental
Drug: High Dose ALKS 5461
Low Dose
Experimental
Drug: Low Dose ALKS 5461
Placebo
Placebo Comparator
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
High Dose ALKS 5461
Drug
Sublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
High Dose
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Baseline and 5 weeks for each stage
Secondary Outcomes
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 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).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
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
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 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
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
70 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Sanjeev Pathak, MD
Alkermes, Inc.
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Alkermes Investigational Site
Birmingham
Alabama
35226
United States
Alkermes Investigational Site
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
This was a Sequential Parallel Comparison Design (SPCD) study comprised of 2 stages. In Stage 1 subjects were randomized to ALKS 5461 or placebo (2:2:9). In Stage 2 only placebo non-responders from Stage 1 were re-randomized to ALKS 5461 or placebo (1:1:1). One subject randomized to the PBO group in Stage 1 did not receive study drug.
Recruitment Details
Subjects were diagnosed with major depressive disorder (MDD) and had an inadequate response to 1 or 2 adequate courses of treatment with a commercially available antidepressant therapy (ADT) during the current major depressive episode (MDE). All subjects continued ADT for the duration of the study.
Subjects randomized in Stage 2 are a subset of those randomized to placebo in Stage 1.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00356 subjects
FG00456 subjects
FG00556 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00353 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
All subjects randomized to Stage 1 (i.e., all subjects randomized during the study) who received ≥ 1 dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo S1
Randomized to placebo in Stage 1
BG001
ALKS 5461 0.5mg/0.5mg S1
Randomized to ALKS 0.5mg/0.5mg in Stage 1
BG002
ALKS 5461 2mg/2mg S1
Randomized to ALKS 5461 2/2 in Stage 1
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000265
BG00159
BG00260
BG003384
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00045.8± 11.50
BG00145.0± 13.89
BG00246.2± 12.14
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000182
BG00138
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00033
BG0017
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0001
BG0010
BG002
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
Canada
Title
Measurements
BG00032
BG0014
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
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.
Posted
Least Squares Mean
Standard Error
units on a scale
Baseline and 5 weeks for each stage
ID
Title
Description
OG000
Placebo S1
Randomized to placebo in Stage 1
OG001
ALKS 5461 0.5mg/0.5mg S1
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 1
OG002
ALKS 5461 2mg/2mg S1
Randomized to ALKS 5461 2mg/2mg in Stage 1
OG003
Placebo S2
Randomized to placebo in Stage 2
OG004
ALKS 5461 0.5mg/0.5mg S2
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 2
OG005
ALKS 5461 2mg/2mg S2
Randomized to ALKS 5461 2mg/2mg in Stage 2
Units
Counts
Participants
OG000256
OG00158
OG00259
OG003
Title
Denominators
Categories
Title
Measurements
OG000-11.1± 0.67
OG001-8.4± 1.49
OG002-13.0± 1.50
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
OG003
OG005
Analysis was conducted for each stage separately and overall efficacy was based on combined stage analysis where stage-specific estimates were combined using pre-specified equal weights. Within each stage ALKS 5461 2mg/2mg was compared to placebo (i.e., ALKS 5461 2mg/2mg S1 vs Placebo S1; and ALKS 5461 2mg/2mg S2 vs Placebo S2. The pre-specified order of hypothesis tests was ALKS 5461 2/2 compared to placebo followed by ALKS 5461 0.5mg/0.5mg compared to placebo.
Mixed Models Analysis
ALKS 5461 was compared to pbo using stage-specific MMRM for MADRS-10 Change from Baseline. Model-derived estimates were combined using equal weights.
0.109
Hypothesis tests were two-sided with an alpha of 0.05. Control of type 1 error inflation due to multiplicity was achieved by pre-specifying a fixed sequence for statistical tests.
Least squares mean difference
-1.8
Standard Error of the Mean
1.14
2-Sided
95
-4.1
Secondary
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).
Stage 1 Full Analysis Set (FAS) consisted of subjects who took at least 1 dose of study drug and had at least 1 postbaseline assessment of MADRS in Stage 1. Stage 2 FAS consisted of Stage 1 placebo non-responders who entered Stage 2 and who received at least 1 dose of study drug and had at least 1 postbaseline assessment of MADRS in Stage 2.
Posted
Count of Participants
Participants
Baseline and 5 weeks for each stage
ID
Title
Description
OG000
Placebo S1
Randomized to placebo in Stage 1
OG001
ALKS 5461 0.5mg/0.5mg S1
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 1
OG002
ALKS 5461 2mg/2mg S1
Secondary
Remission Rate
The proportion of subjects achieving remission, defined as a MADRS-10 score of \
Stage 1 Full Analysis Set (FAS) consisted of subjects who took at least 1 dose of study drug and had at least 1 postbaseline assessment of MADRS in Stage 1. Stage 2 FAS consisted of Stage 1 placebo non-responders who entered Stage 2 and who received at least 1 dose of study drug and had at least 1 postbaseline assessment of MADRS in Stage 2.
Posted
Count of Participants
Participants
Baseline and 5 weeks for each stage
ID
Title
Description
OG000
Placebo S1
Randomized to placebo in Stage 1
OG001
ALKS 5461 0.5mg/0.5mg S1
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 1
OG002
ALKS 5461 2mg/2mg S1
Randomized to ALKS 5461 2mg/2mg in Stage 1
OG003
Placebo S2
Randomized to placebo in Stage 2
Secondary
Number of Subjects With Adverse Events (AEs)
Safety population consists of all randomized subjects who received at least 1 dose of study drug.
Posted
Count of Participants
Participants
5 weeks for Stage 1 and 6 weeks for Stage 2
ID
Title
Description
OG000
Placebo S1
Randomized to placebo in Stage 1
OG001
ALKS 5461 0.5mg/0.5mg S1
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 1
OG002
ALKS 5461 2mg/2mg S1
Randomized to ALKS 5461 2mg/2mg in Stage 1
OG003
Placebo S2
Randomized to placebo in Stage 2
OG004
ALKS 5461 0.5mg/0.5mg S2
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 2
OG005
Time Frame
5 weeks for Stage 1 and 6 weeks for Stage 2
Description
Safety population consists of all randomized subjects who received at least 1 dose of study drug.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo S1
Randomized to placebo in Stage 1
0
265
1
265
81
265
EG001
ALKS 5461 0.5mg/0.5mg S1
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 1
0
59
0
59
32
59
EG002
ALKS 5461 2mg/2mg S1
Randomized to ALKS 5461 2mg/2mg in Stage 1
0
60
0
60
36
60
EG003
Placebo S2
Randomized to placebo in Stage 2
0
56
0
56
11
56
EG004
ALKS 5461 0.5mg/0.5mg S2
Randomized to ALKS 5461 0.5mg/0.5mg in Stage 2
0
56
0
56
13
56
EG005
ALKS 5461 2mg/2mg S2
Randomized to ALKS 5461 2mg/2mg in Stage 2
0
56
0
56
22
56
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 18.0
Non-systematic Assessment
EG0001 events1 affected265 at risk
EG0010 events0 affected59 at risk
EG0020 events0 affected60 at risk
EG0030 events0 affected56 at risk
EG0040 events0 affected56 at risk
EG0050 events0 affected56 at risk
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Nausea
Gastrointestinal disorders
MedDRA 18.0
Non-systematic Assessment
EG00017 events17 affected265 at risk
EG00115 events14 affected59 at risk
EG00224 events17 affected60 at risk
EG0031 events1 affected56 at risk
EG0046 events5 affected56 at risk
EG0058 events8 affected56 at risk
Constipation
Gastrointestinal disorders
MedDRA (18.0)
Non-systematic Assessment
EG0004 events4 affected265 at risk
EG0014 events4 affected59 at risk
EG00210 events10 affected60 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (18.0)
Non-systematic Assessment
EG0004 events4 affected265 at risk
EG0014 events4 affected59 at risk
EG0026 events6 affected60 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (18.0)
Non-systematic Assessment
EG00011 events11 affected265 at risk
EG0012 events2 affected59 at risk
EG0026 events5 affected60 at risk
EG003
Fatigue
General disorders
MedDRA (18.0)
Non-systematic Assessment
EG0005 events5 affected265 at risk
EG0014 events3 affected59 at risk
EG0022 events2 affected60 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (18.0)
Non-systematic Assessment
EG0006 events6 affected265 at risk
EG0011 events1 affected59 at risk
EG0022 events2 affected60 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (18.0)
Non-systematic Assessment
EG0007 events6 affected265 at risk
EG0011 events1 affected59 at risk
EG0020 events0 affected60 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (18.0)
Non-systematic Assessment
EG0001 events1 affected265 at risk
EG0010 events0 affected59 at risk
EG0023 events3 affected60 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (18.0)
Non-systematic Assessment
EG00010 events9 affected265 at risk
EG0014 events4 affected59 at risk
EG0029 events8 affected60 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (18.0)
Non-systematic Assessment
EG0007 events7 affected265 at risk
EG0015 events5 affected59 at risk
EG0026 events6 affected60 at risk
EG003
Headache
Nervous system disorders
MedDRA (18.0)
Non-systematic Assessment
EG00023 events22 affected265 at risk
EG00110 events7 affected59 at risk
EG0025 events5 affected60 at risk
EG003
Sedation
Nervous system disorders
MedDRA (18.0)
Non-systematic Assessment
EG0003 events3 affected265 at risk
EG0012 events2 affected59 at risk
EG0026 events5 affected60 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (18.0)
Non-systematic Assessment
EG0007 events7 affected265 at risk
EG0011 events1 affected59 at risk
EG0025 events5 affected60 at risk
EG003
Abnormal dreams
Psychiatric disorders
MedDRA (18.0)
Non-systematic Assessment
EG0007 events7 affected265 at risk
EG0013 events3 affected59 at risk
EG0023 events3 affected60 at risk
EG003
Irritability
Psychiatric disorders
MedDRA (18.0)
Non-systematic Assessment
EG0000 events0 affected265 at risk
EG0010 events0 affected59 at risk
EG0023 events3 affected60 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (18.0)
Non-systematic Assessment
EG0004 events4 affected265 at risk
EG0010 events0 affected59 at risk
EG0024 events4 affected60 at risk
EG003
Hot flush
Vascular disorders
MedDRA (18.0)
Non-systematic Assessment
EG0005 events5 affected265 at risk
EG0010 events0 affected59 at risk
EG0023 events3 affected60 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Should an Investigator desire to disclose study results, Sponsor will review the results disclosure prior to public release and can embargo the disclosure for a period of at least 60 days. Revisions to the disclosure will be negotiated in good faith. For a multicenter study the Investigators agree to publish/publicly present the results together with the other sites for the 12 month period after study results are available unless Sponsor grants written permission in advance.
Point of Contact
Title
Organization
Phone
Extension
Email
Eva Stroynowski
Alkermes
781-609-7000
Eva.Stroynowski@alkermes.com
ID
Term
D003865
Depressive Disorder, Major
D003863
Depression
Ancestor Terms
ID
Term
D003866
Depressive Disorder
D019964
Mood Disorders
D001523
Mental Disorders
D001526
Behavioral Symptoms
D001519
Behavior
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C000618349
ALKS 5461
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
52 subjects
FG00550 subjects
4 subjects
FG0056 subjects
0 subjects
FG0040 subjects
FG0051 subjects
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0041 subjects
FG0052 subjects
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0052 subjects
Physician Decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
Pregnancy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
Psychiatrist decision to try new tx
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
Non-adherence with study visits
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0051 subjects
45.7
± 11.97
40
BG003260
Male
BG00083
BG00121
BG00220
BG003124
4
BG00344
Not Hispanic or Latino
BG000232
BG00152
BG00256
BG003340
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
0
BG0031
Asian
BG0003
BG0011
BG0022
BG0036
Native Hawaiian or Other Pacific Islander
BG0002
BG0010
BG0020
BG0032
Black or African American
BG00077
BG00116
BG00216
BG003109
White
BG000182
BG00142
BG00242
BG003266
More than one race
BG0000
BG0010
BG0020
BG0030
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
4
BG00340
United States
Title
Measurements
BG000218
BG00153
BG00252
BG003323
Australia
Title
Measurements
BG00015
BG0012
BG0024
BG00321
54
OG00455
OG00554
-2.2
± 1.08
OG004-4.8± 1.27
OG005-3.9± 1.13
0.4
Estimates below zero favor ALKS 5461.
Superiority
OG000
OG001
OG003
OG004
Analysis was conducted for each stage separately and overall efficacy was based on combined stage analysis where stage-specific estimates were combined using pre-specified equal weights. Within each stage ALKS 5461 0.5mg/0.5mg was compared to placebo (i.e., ALKS 5461 0.5mg/0.5mg S1 vs Placebo S1; and ALKS 5461 0.5mg/0.5mg S2 vs Placebo S2). The pre-specified order of hypothesis tests was ALKS 5461 2/2 compared to placebo followed by ALKS 5461 0.5/0.5 compared to placebo.
Mixed Models Analysis
ALKS 5461 was compared to pbo using stage-specific MMRM for MADRS-10 Change from Baseline. Model-derived estimates were combined using equal weights.
0.975
Hypothesis tests were two-sided with an alpha of 0.05. Control of type 1 error inflation due to multiplicity was achieved by pre-specifying a fixed sequence for statistical tests.