A Study to Evaluate ALKS 5461 in Subjects With Major Depr... | NCT01500200 | Trialant
NCT01500200
Sponsor
Alkermes, Inc.
Status
Completed
Last Update Posted
May 21, 2019Actual
Enrollment
142Actual
Phase
Phase 2
Conditions
Major Depressive Disorder
Interventions
ALKS 5461
Placebo
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT01500200
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
ALK5461-202
Secondary IDs
Not provided
Brief Title
A Study to Evaluate ALKS 5461 in Subjects With Major Depressive Disorder (MDD)
Official Title
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
Acronym
Not provided
Organization
Alkermes, Inc.INDUSTRY
Status Module
Record Verification Date
Apr 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
Dec 2011
Primary Completion Date
Mar 2013Actual
Completion Date
Mar 2013Actual
First Submitted Date
Dec 22, 2011
First Submission Date that Met QC Criteria
Dec 27, 2011
First Posted Date
Dec 28, 2011Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 1, 2019
Results First Submitted that Met QC Criteria
Apr 26, 2019
Results First Posted Date
May 21, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Nov 8, 2013
Certification/Extension First Submitted that Passed QC Review
Nov 8, 2013
Certification/Extension First Posted Date
Dec 3, 2013Estimated
Last Update Submitted Date
Apr 26, 2019
Last Update Posted Date
May 21, 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 of ALKS 5461 when administered daily for 4 weeks to adults with Major Depressive Disorder (MDD) and inadequate response to antidepressant therapy.
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.
Conditions Module
Conditions
Major Depressive Disorder
Keywords
Not provided
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 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
142Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
ALKS 5461
Experimental
Drug: ALKS 5461
Placebo
Placebo Comparator
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
ALKS 5461
Drug
Two active tablets, given daily
ALKS 5461
Placebo
Outcomes Module
Primary Outcomes
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 Outcomes
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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)
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.
See Also Links
Not provided
Available IPD Information
Not provided
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 placebo 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.
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
Oceanside
California
92056
United States
Alkermes Investigational Site
Santa Ana
California
92701
United States
Alkermes Investigational Site
Torrance
California
90502
United States
Alkermes Investigational Site
Fort Myers
Florida
33912
United States
Alkermes Investigational Site
Lauderhill
Florida
33319
United States
Alkermes Investigational Site
Leesburg
Florida
34748
United States
Alkermes Investigational Site
North Miami
Florida
33161
United States
Alkermes Investigational Site
St. Petersburg
Florida
33716
United States
Alkermes Investigational Site
Atlanta
Georgia
30308
United States
Alkermes Investigational Site
Hoffman Estates
Illinois
60169
United States
Alkermes Investigational Site
Baltimore
Maryland
21285
United States
Alkermes Investigational Site
Boston
Massachusetts
02135
United States
Alkermes Investigational Site
Haverhill
Massachusetts
01830
United States
Alkermes Investigational Site
Berlin
New Jersey
08009
United States
Alkermes Investigational Site
Brooklyn
New York
11241
United States
Alkermes Investigational Site
New York
New York
10021
United States
Alkermes Investigational Site
Canton
Ohio
44718
United States
Alkermes Investigational Site
Dayton
Ohio
45417
United States
Alkermes Investigational Site
Oklahoma City
Oklahoma
73112
United States
Alkermes Investigational Site
Philadelphia
Pennsylvania
19104
United States
Alkermes Investigational Site
Charleston
South Carolina
29407
United States
Alkermes Investigational Site
Austin
Texas
78754
United States
Alkermes Investigational Site
Dallas
Texas
75235
United States
Alkermes Investigational Site
Houston
Texas
77081
United States
Alkermes Investigational Site
San Antonio
Texas
78229
United States
Alkermes Investigational Site
Bellevue
Washington
98007
United States
FG002
ALKS 5461 8mg/8mg S1
Received ALKS 5461 8mg/8mg in Stage 1
FG003
Placebo S2
Received placebo in Stage 2
FG004
ALKS 5461 2mg/2mg S2
Received ALKS 5461 2mg/2mg in Stage 2
FG005
ALKS 5461 8mg/8mg S2
Received ALKS 5461 8mg/8mg in Stage 2
FG00098 subjects
FG00124 subjects
FG00219 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG00090 subjects
FG00118 subjects
FG00213 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG0008 subjects
FG0016 subjects
FG0026 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0014 subjects
FG0025 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Lost to Follow-up
FG0002 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0003 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Noncompliance with Study Drug
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Physician Decision
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Stage 2
Type
Comment
Milestone Data
STARTED
Subjects in Stage 2 are a subset of those randomized to placebo in Stage 1.
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00320 subjects
FG00423 subjects
FG00522 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00320 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 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 ≥ dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo S1
Received placebo in Stage 1
BG001
ALKS 5461 2mg/2mg S1
Received ALKS 5461 2mg/2mg in Stage 1
BG002
ALKS 5461 8mg/8mg S1
Received ALKS 5461 8mg/8mg in Stage 1
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00098
BG00124
BG00219
BG003141
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
BG00046.6± 11.0
BG00145.2± 10.9
BG00245.8± 11.9
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00068
BG00117
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
Count of participants
Title
Denominators
Categories
United States
Title
Measurements
BG00098
BG00124
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 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.
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 HAM-D17 assessment in the respective stage. Two subjects randomized to 8/8 in Stage 1 received 2/2. These subjects are included in the 8/8 group for efficacy analysis.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline and 4 weeks for each stage
ID
Title
Description
OG000
Placebo S1
Subjects randomized to placebo in Stage 1
OG001
ALKS 5461 2mg/2mg S1
Subjects randomized to ALKS 5461 2mg/2mg in Stage 1
OG002
ALKS 5461 8mg/8mg S1
Subjects randomized to ALKS 5461 8mg/8mg in Stage 1
OG003
Placebo S2
Subjects randomized to placebo in Stage 2
OG004
ALKS 5461 2mg/2mg S2
Subjects randomized to ALKS 5461 2mg/2mg in Stage 2
OG005
ALKS 5461 8mg/8mg S2
Subjects randomized to ALKS 5461 8mg/8mg in Stage 2
Units
Counts
Participants
OG00095
OG00120
OG00220
OG003
Title
Denominators
Categories
Title
Measurements
OG000-7.1± 0.6
OG001-9.3± 1.5
OG002-6.6± 1.6
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
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 weights (0.6/0.4 for Stage 1/Stage 2). 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.
Mixed Models Analysis
ALKS 5461 was compared to PBO using stage-specific MMRM for change from Baseline. Model-derived estimates were combined using pre-specified weights.
0.014
Hypothesis tests were two-sided with an alpha of 0.5.
Secondary
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.
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 HAM-D17 assessment in the respective stage.
Posted
Count of Participants
Participants
4 weeks for each stage
ID
Title
Description
OG000
Placebo S1
Subjects randomized to placebo in Stage 1
OG001
ALKS 5461 2mg/2mg S1
Subjects randomized to ALKS 5461 2mg/2mg in Stage 1
OG002
ALKS 5461 8mg/8mg S1
Secondary
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.
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 HAM-D17 assessment in the respective stage. Two subjects randomized to 8/8 in Stage 1 received 2/2. These subjects are included in the 8/8 group for efficacy analysis.
Posted
Least Squares Mean
Standard Error
score on a scale
4 weeks for each stage
ID
Title
Description
OG000
Placebo S1
Subjects randomized to placebo in Stage 1
OG001
ALKS 5461 2mg/2mg S1
Subjects randomized to ALKS 5461 2mg/2mg in Stage 1
OG002
ALKS 5461 8mg/8mg S1
Subjects randomized to ALKS 5461 8mg/8mg in Stage 1
Secondary
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."
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 HAM-D17 assessment in the respective stage. Two subjects randomized to 8/8 in Stage 1 received 2/2. These subjects are included in the 8/8 group for efficacy analysis.
Posted
Least Squares Mean
Standard Error
score on a scale
4 weeks for each stage
ID
Title
Description
OG000
Placebo S1
Subjects randomized to placebo in Stage 1
OG001
ALKS 5461 2mg/2mg S1
Subjects randomized to ALKS 5461 2mg/2mg in Stage 1
OG002
ALKS 5461 8mg/8mg S1
Subjects randomized to ALKS 5461 8mg/8mg in Stage 1
Time Frame
4 weeks for each stage
Description
The safety population includes all subjects who were randomized and received at least 1 dose of study drug. Two subjects randomized to 8/8 in Stage 1 received 2/2. These subjects are included in the 2/2 group for the safety analysis.
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
Received placebo in Stage 1
0
98
1
98
42
98
EG001
ALKS 5461 2mg/2mg S1
Received ALKS 5461 2mg/2mg in Stage 1
0
24
1
24
15
24
EG002
ALKS 5461 8mg/8mg S1
Received ALKS 5461 8mg/8mg in Stage 1
0
19
0
19
18
19
EG003
Placebo S2
Received placebo in Stage 2
0
20
0
20
11
20
EG004
ALKS 5461 2mg/2mg S2
Received ALKS 5461 2mg/2mg in Stage 1
0
23
1
23
19
23
EG005
ALKS 5461 8mg/8mg S2
Received ALKS 5461 8mg/8mg in Stage 1
0
22
0
22
17
22
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Multiple drug overdose intentional
Psychiatric disorders
MedDRA (15.0)
Non-systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected24 at risk
EG0020 events0 affected19 at risk
EG0030 events0 affected20 at risk
EG004
Drug withdrawal syndrome
Psychiatric disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Intraocular melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Dry eye
Eye disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG0030 events0 affected20 at risk
EG0040 events0 affected23 at risk
EG0050 events0 affected22 at risk
Miosis
Eye disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Vision blurred
Eye disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0007 events6 affected98 at risk
EG0016 events5 affected24 at risk
EG00210 events9 affected19 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0006 events5 affected98 at risk
EG0012 events2 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0015 events3 affected24 at risk
EG0027 events7 affected19 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0006 events6 affected98 at risk
EG0012 events2 affected24 at risk
EG0022 events2 affected19 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0004 events4 affected98 at risk
EG0010 events0 affected24 at risk
EG0022 events2 affected19 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Hypoaesthesia oral
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (15.0)
Non-systematic Assessment
EG0006 events5 affected98 at risk
EG0011 events1 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Fatigue
General disorders
MedDRA (15.0)
Non-systematic Assessment
EG0004 events4 affected98 at risk
EG0012 events2 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Feeling abnormal
General disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Product taste abnormal
General disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (15.0)
Non-systematic Assessment
EG0002 events2 affected98 at risk
EG0010 events0 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Poisoning
Injury, poisoning and procedural complications
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Blood pressure increased
Investigations
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0011 events1 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Blood thyroid stimulating hormone increased
Investigations
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Electrocardiogram RR interval prolonged
Investigations
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Weight increased
Investigations
MedDRA (15.0)
Non-systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA (15.0)
Non-systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0022 events2 affected19 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (15.0)
Non-systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected24 at risk
EG0022 events1 affected19 at risk
EG003
Muscle twitching
Musculoskeletal and connective tissue disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (15.0)
Non-systematic Assessment
EG0005 events5 affected98 at risk
EG0015 events4 affected24 at risk
EG00210 events9 affected19 at risk
EG003
Headache
Nervous system disorders
MedDRA (15.0)
Non-systematic Assessment
EG00019 events14 affected98 at risk
EG0011 events1 affected24 at risk
EG0028 events5 affected19 at risk
EG003
Sedation
Nervous system disorders
MedDRA (15.0)
Non-systematic Assessment
EG0002 events2 affected98 at risk
EG0014 events3 affected24 at risk
EG0025 events5 affected19 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0023 events3 affected19 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0022 events2 affected19 at risk
EG003
Somnolence
Nervous system disorders
MedDRA (15.0)
Non-systematic Assessment
EG0002 events2 affected98 at risk
EG0010 events0 affected24 at risk
EG0022 events2 affected19 at risk
EG003
Agitation
Psychiatric disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA (15.0)
Non-systematic Assessment
EG0001 events1 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Suicidal ideation
Psychiatric disorders
MedDRA (15.0)
Non-systematic Assessment
EG0003 events1 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Euphoric mood
Psychiatric disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0012 events2 affected24 at risk
EG0020 events0 affected19 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (15.0)
Non-systematic Assessment
EG0003 events3 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA (15.0)
Non-systematic Assessment
EG0000 events0 affected98 at risk
EG0010 events0 affected24 at risk
EG0021 events1 affected19 at risk
EG003
Two subjects randomized to 8/8 received 2/2 and are presented in the Participant Flow, Baseline, and AE tables by actual treatment received. For the outcome measures, subjects were analyzed by randomization treatment assignment.
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
Ancestor Terms
ID
Term
D003866
Depressive Disorder
D019964
Mood Disorders
D001523
Mental Disorders
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
18 subjects
FG00518 subjects
5 subjects
FG0054 subjects
0 subjects
FG0045 subjects
FG0054 subjects
46.3
± 11.1
11
BG00396
Male
BG00030
BG0017
BG0028
BG00345
0
BG0030
Asian
BG0000
BG0010
BG0020
BG0030
Native Hawaiian or Other Pacific Islander
BG0001
BG0010
BG0020
BG0031
Black or African American
BG00023
BG0019
BG0026
BG00338
White
BG00074
BG00115
BG00213
BG003102
More than one race
BG0000
BG0010
BG0020
BG0030
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
19
BG003141
20
OG00423
OG00522
-1.5
± 1.1
OG004-5.2± 1.2
OG005-3.3± 1.1
Superiority
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 weights (0.6/0.4 for Stage 1/Stage 2). Within each stage ALKS 5461 8mg/8mg was compared to placebo (i.e., ALKS 5461 8mg/8mg S1 vs Placebo S1; and ALKS 5461 8mg/8mg S2 vs Placebo S2.
Mixed Models Analysis
ALKS 5461 was compared to PBO using stage-specific MMRM for change from Baseline. Model-derived estimates were combined using pre-specified weights.
0.699
Hypothesis tests were two-sided with an alpha of 0.05.
Superiority
Subjects randomized to ALKS 5461 8mg/8mg in Stage 1
OG003
Placebo S2
Subjects randomized to placebo in Stage 2
OG004
ALKS 5461 2mg/2mg S2
Subjects randomized to ALKS 5461 2mg/2mg in Stage 2
OG005
ALKS 5461 8mg/8mg S2
Subjects randomized to ALKS 5461 8mg/8mg in Stage 2
Units
Counts
Participants
OG00090
OG00117
OG00214
OG00320
OG00418
OG00518
Title
Denominators
Categories
Title
Measurements
Yes
OG00023
OG0018
OG0025
OG0033
OG0046
OG0055
No
OG00067
OG0019
OG0029
OG00317
OG004
OG003
Placebo S2
Subjects randomized to placebo in Stage 2
OG004
ALKS 5461 2mg/2mg S2
Subjects randomized to ALKS 5461 2mg/2mg in Stage 2
OG005
ALKS 5461 8mg/8mg S2
Subjects randomized to ALKS 5461 8mg/8mg in Stage 2
Units
Counts
Participants
OG00095
OG00120
OG00220
OG00320
OG00423
OG00522
Title
Denominators
Categories
Title
Measurements
OG000-9.6± 0.9
OG001-13.3± 2.2
OG002-11.3± 2.3
OG003-2.1± 1.6
OG004-8.8± 1.7
OG005-4.7± 1.7
OG003
Placebo S2
Subjects randomized to placebo in Stage 2
OG004
ALKS 5461 2mg/2mg S2
Subjects randomized to ALKS 5461 2mg/2mg in Stage 2
OG005
ALKS 5461 8mg/8mg S2
Subjects randomized to ALKS 5461 8mg/8mg in Stage 2