A Study of ALKS 3831 in Adults With Schizophrenia | NCT01903837

Status Module

Oversight Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Low Dose	Experimental	Olanzapine + low dose samidorphan tablets taken once daily	Drug: Samidorphan (Low Dose) Drug: Olanzapine
Medium Dose	Experimental	Olanzapine + medium dose samidorphan tablets taken once daily	Drug: Samidorphan (Medium Dose) Drug: Olanzapine
High Dose	Experimental	Olanzapine + high dose samidorphan tablets taken once daily	Drug: Samidorphan (High Dose) Drug: Olanzapine
Placebo	Placebo Comparator	Olanzapine + placebo tablets taken once daily	Drug: Placebo Drug: Olanzapine

Name	Type	Description	Arm Group Labels	Other Names
Samidorphan (Low Dose)	Drug	Tablets taken once daily	Low Dose	Low dose samidorphan (ALKS 33)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Absolute Change in Total Positive and Negative Syndrome Scale (PANSS) Score	Change from baseline (Day 8) to Day 92 (end of study Part A). The PANSS is a 30-item scale measuring severity of schizophrenia symptoms. Symptom severity for each item is rated on a 7-point scale (1 = absent; 7 = extreme), and the total score is added together, with a minimum score of 30 and a maximum score of 210. A higher score indicates more severe symptoms, while a lower score indicates less severe symptoms.	Baseline (Day 8) to Day 92 (end of study Part A)

Secondary Outcomes

Measure	Description	Time Frame
Percent Change in Body Weight (Kilogram) From Baseline to Day 92	Percent change from baseline (Day 8) to the end of Part A (Day 92)	Baseline (Day 8) to Day 92 (end of study Part A)
Absolute Change in Body Weight (kg) From Baseline to Day 92

Eligibility Module

Name	Affiliation	Role
Bernard L. Silverman, MD	Alkermes, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Alkermes Investigational Site		Little Rock	Arkansas	72211	United States
Alkermes Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30845818	Result	Martin WF, Correll CU, Weiden PJ, Jiang Y, Pathak S, DiPetrillo L, Silverman BL, Ehrich EW. Mitigation of Olanzapine-Induced Weight Gain With Samidorphan, an Opioid Antagonist: A Randomized Double-Blind Phase 2 Study in Patients With Schizophrenia. Am J Psychiatry. 2019 Jun 1;176(6):457-467. doi: 10.1176/appi.ajp.2018.18030280. Epub 2019 Mar 8.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Olz + Placebo/ Olz+Sam 20mg	Part A: Olanzapine (dose level determined by Investigator) + placebo tablets taken once daily Part B: Olanzapine (dose level determined by Investigator) + 20mg Samidorphan tablets taken once daily Subjects were transitioned from placebo in Part A to 20mg Samidorphan in Part B
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 13, 2014	Jun 10, 2021

Arm/Group Information

ID	Title	Description
BG000	Olz + Placebo	Olanzapine (dose level determined by Investigator) and placebo tablets taken once daily
BG001	Olz + Sam 5mg	Olanzapine (dose level determined by Investigator) and 5mg Samidorphan tablets taken once daily
BG002	Olz + Sam 10mg	Olanzapine (dose level determined by Investigator) and 10mg Samidorphan tablets taken once daily
BG003	Olz + Sam 20mg	Olanzapine (dose level determined by Investigator) and 20mg Samidorphan tablets taken once daily
BG004	Total	Total of all reporting groups

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
	BG00040.3± 8.14 BG00137.9± 8.62 BG00238.1± 8.00 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00022 BG00120 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0004 BG0015 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00060 BG00168 BG002

Height

Mean

Standard Deviation

centimeters

Title

Denominators

Categories

Title	Measurements
	BG000173.4± 8.07 BG001173.5± 10.76 BG002

Weight

Mean

Standard Deviation

kilograms

Title

Denominators

Categories

Title	Measurements
	BG00075.6± 12.30 BG00177.5± 13.07 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kilograms/meters^2

Title

Denominators

Categories

Title	Measurements
	BG00025.1± 3.40 BG00125.7± 3.18 BG002

Body Mass Index (BMI) Group

Count of Participants

Participants

Title

Denominators

Categories

Underweight (<18.5)

Title	Measurements
	BG0001 BG0010 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

Absolute Change in Total Positive and Negative Syndrome Scale (PANSS) Score

Change from baseline (Day 8) to Day 92 (end of study Part A).

The PANSS is a 30-item scale measuring severity of schizophrenia symptoms. Symptom severity for each item is rated on a 7-point scale (1 = absent; 7 = extreme), and the total score is added together, with a minimum score of 30 and a maximum score of 210. A higher score indicates more severe symptoms, while a lower score indicates less severe symptoms.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day 8) to Day 92 (end of study Part A)

ID	Title	Description
OG000	Part A FAS 1 - Olz + Placebo	Subjects who were randomized to olanzapine + placebo in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG001	Part A FAS 1 - Olz + Sam 5mg	Subjects who were randomized to olanzapine + samidorphan 5mg in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG002	Part A FAS 1- Olz+ Sam 10mg	Subjects who were randomized to olanzapine + samidorphan 10mg in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG003	Part A FAS 1- Olz+ Sam 20mg	Subjects who were randomized to olanzapine + samidorphan 20mg in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score

Units	Counts
Participants	OG00074 OG00175 OG00283 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-2.9± 0.82 OG001-1.5± 0.85 OG002-2.7± 0.79 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 OG002 OG003		Least Square Mean Difference		0.3		Least Square Mean Difference	0.3	Standard Error of the Mean	1.17	2-Sided	95	-2.0	2.6					Equivalence	Equivalence margin of 10 points

Secondary

Percent Change in Body Weight (Kilogram) From Baseline to Day 92

Percent change from baseline (Day 8) to the end of Part A (Day 92)

Full Analysis Set (FAS) 1 efficacy analysis population included all randomized subjects who received at least one dose of study drug and had at least one postbaseline assessment of Positive and Negative Syndrome Scale (PANSS) total score. FAS 2 efficacy analysis population included all FAS 1 subjects who gained weight during the 1-week OLZ lead-in period prior to randomization and had at least one postbaseline weight assessment.

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline (Day 8) to Day 92 (end of study Part A)

ID	Title	Description
OG000	Part A FAS 1 - Olz + Placebo	Subjects who were randomized to olanzapine + placebo in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG001	Part A FAS 1 - Olz + Sam 5mg	Subjects who were randomized to olanzapine + samidorphan 5mg in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG002	Part A FAS 1- Olz + Sam 10mg	Subjects who were randomized to olanzapine + samidorphan 10mg in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score

Secondary

Absolute Change in Body Weight (kg) From Baseline to Day 92

Change from randomization (Day 8) to the end of Part A (Week 12; Day 92)

Posted

Least Squares Mean

95% Confidence Interval

Baseline (Day 8) to Day 92 (end of study Part A)

ID	Title	Description
OG000	Part A FAS 1- Olz + Placebo	Subjects who were randomized to olanzapine + placebo in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG001	Part A FAS 1- Olz + Sam 5mg	Subjects who were randomized to olanzapine + 5mg samidorphan in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG002	Part A FAS 1- Olz + Sam 10mg	Subjects who were randomized to olanzapine + 10mg samidorphan in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score

Secondary

Percentage of Subjects Exhibiting Significant Weight Gain at Day 92

Significant weight gain will include a >=5%, >= 7%, or >=10% gain in body weight from baseline (Day 8) to Day 92 (end of study Part A)

Posted

Count of Participants

Participants

Baseline (Day 8) to Day 92 (end of study Part A)

ID	Title	Description
OG000	Part A FAS 1- Olz + Placebo	Subjects who were randomized to olanzapine + placebo in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG001	Part A FAS 1- Olz + Sam 5mg	Subjects who were randomized to olanzapine + samidorphan 5mg in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG002	Part A FAS 1- Olz + Sam 10mg

Secondary

Change in Clinical Global Impressions - Severity (CGI-S) From Baseline to Day 92

Change in CGI-S score from baseline (Day 8) to the end of Part A (Week 12; Day 92).

The CGI-S is a 7-point scale intended to measure the severity of a patient's illness at the time of assessment. Scores range from 1 (normal) to 7(extremely ill), so a higher score is correlative to more severe illness.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day 8) to Day 92 (end of study Part A)

ID	Title	Description
OG000	Part A FAS 1 - OLZ + Placebo	Subjects who were randomized to olanzapine + placebo in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG001	Part A FAS 1 - Olz + Sam 5mg	Subjects who were randomized to olanzapine + samidorphan 5mg in study Part A, received at least one dose of study drug, and had at least one post-baseline assessment of PANSS total score
OG002	Part A FAS 1- Olz + Sam 10mg

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A- Olz + Placebo	Olanzapine (dose level determined by Investigator) + placebo tablets taken once daily	75	2	75	33	75
EG001	Part A-Olz + Sam 5mg	Olanzapine (dose level determined by Investigator) + 5mg samidorphan tablets taken once daily	80	3	80	25	80
EG002	Part A- Olz + Sam 10mg	Olanzapine (dose level determined by Investigator) + 10mg Samidorphan tablets taken once daily	86	4	86	33	86
EG003	Part A- Olz + Sam 20mg	Olanzapine (dose level determined by Investigator) + 20mg samidorphan tablets taken once daily	68	4	68	33	68
EG004	Part B-Olz +Placebo/ Olz+Sam 20mg	Olanzapine (dose level determined by Investigator) + 20mg Samidorphan tablets taken once daily Subjects were transitioned from placebo in Part A to 20mg Samidorphan in Part B	54	1	54	11	54
EG005	Part B- Olz + Sam 5mg / Olz +Sam 5mg	Olanzapine (dose level determined by Investigator) + 5mg samidorphan tablets taken once daily	52	1	52	10	52
EG006	Part B- Olz + Sam 10mg/ Olz + Sam 10mg	Olanzapine (dose level determined by Investigator) + 10mg Samidorphan tablets taken once daily	57	1	57	11	57
EG007	Part B-Olz + Sam 20mg/ Olz + Sam 20mg	Olanzapine (dose level determined by Investigator) + 20mg samidorphan tablets taken once daily	55	0	55	12	55

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Arthralgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 affected75 at risk EG0010 affected80 at risk EG0021 affected86 at risk EG0030 affected68 at risk EG0040 affected54 at risk EG0050 affected52 at risk EG0060 affected57 at risk EG0070 affected55 at risk
Ischaemic stroke	Nervous system disorders	Non-systematic Assessment	EG0001 affected75 at risk EG0010 affected80 at risk EG0020 affected86 at risk EG003
Schizophrenia	Psychiatric disorders	Non-systematic Assessment	EG0001 affected75 at risk EG0012 affected80 at risk EG0021 affected86 at risk EG003
Suicidal ideation	Psychiatric disorders	Non-systematic Assessment	EG0000 affected75 at risk EG0011 affected80 at risk EG0020 affected86 at risk EG003
Agitation	Psychiatric disorders	Non-systematic Assessment	EG0000 affected75 at risk EG0010 affected80 at risk EG0021 affected86 at risk EG003
Anxiety	Psychiatric disorders	Non-systematic Assessment	EG0000 affected75 at risk EG0010 affected80 at risk EG0021 affected86 at risk EG003
Subcutaneous abscess	Infections and infestations	Non-systematic Assessment	EG0000 affected75 at risk EG0010 affected80 at risk EG0020 affected86 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Weight increased	Investigations	Non-systematic Assessment	EG0009 affected75 at risk EG0018 affected80 at risk EG0029 affected86 at risk EG0036 affected68 at risk EG0043 affected54 at risk EG0056 affected52 at risk EG0062 affected57 at risk EG0073 affected55 at risk
Weight decreased	Investigations	Non-systematic Assessment	EG0000 affected75 at risk EG0010 affected80 at risk EG0020 affected86 at risk EG003
Somnolence	Nervous system disorders	Non-systematic Assessment	EG0003 affected75 at risk EG00110 affected80 at risk EG00211 affected86 at risk EG003
Sedation	Nervous system disorders	Non-systematic Assessment	EG0003 affected75 at risk EG0010 affected80 at risk EG0024 affected86 at risk EG003
Dizziness	Nervous system disorders	Non-systematic Assessment	EG0001 affected75 at risk EG0010 affected80 at risk EG0023 affected86 at risk EG003
Headache	Nervous system disorders	Non-systematic Assessment	EG0004 affected75 at risk EG0013 affected80 at risk EG0021 affected86 at risk EG003
Tremor	Nervous system disorders	Non-systematic Assessment	EG0004 affected75 at risk EG0010 affected80 at risk EG0020 affected86 at risk EG003
Insomnia	Psychiatric disorders	Non-systematic Assessment	EG0004 affected75 at risk EG0012 affected80 at risk EG0022 affected86 at risk EG003
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0004 affected75 at risk EG0015 affected80 at risk EG0024 affected86 at risk EG003
Dry mouth	Gastrointestinal disorders	Non-systematic Assessment	EG0004 affected75 at risk EG0012 affected80 at risk EG0025 affected86 at risk EG003
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0001 affected75 at risk EG0010 affected80 at risk EG0025 affected86 at risk EG003
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG0000 affected75 at risk EG0010 affected80 at risk EG0020 affected86 at risk EG003
Increased appetite	Metabolism and nutrition disorders	Non-systematic Assessment	EG0006 affected75 at risk EG0015 affected80 at risk EG0025 affected86 at risk EG003
Nasopharyngitis	Infections and infestations	Non-systematic Assessment	EG0000 affected75 at risk EG0010 affected80 at risk EG0020 affected86 at risk EG003
Toothache	Gastrointestinal disorders	Non-systematic Assessment	EG0004 affected75 at risk EG0010 affected80 at risk EG0020 affected86 at risk EG003

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders

ID	Term
D001569	Benzodiazepines
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Term
C000606131	3-carboxamido-4-hydroxynaltrexone
D000077152	Olanzapine