Study to Evaluate the Efficacy of ALKS 3831 on Body Weigh... | NCT03187769

NCT03187769

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
ALKS 3831	Experimental	Coated bilayer tablet	Drug: ALKS 3831
Olanzapine	Active Comparator	Coated bilayer tablet	Drug: Olanzapine

Name	Type	Description	Arm Group Labels	Other Names
ALKS 3831	Drug	Olanzapine + samidorphan, daily oral dosing	ALKS 3831

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Body Weight at Week 12	The efficacy analyses were performed using the Final Analysis Set which is defined as all randomized subjects who received one dose of study drug and had at least 1 primary efficacy assessment after administration of study drug	Baseline and 12 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Subjects With ≥10% Weight Gain at Week 12	Percentage of weight gain is analyzed based on the subject's assessment status (≥10% vs <10%) at Week 12 using a logistic regression model including treatment group, diagnosis (schizophrenia/schizophreniform disorder vs bipolar I disorder), region (US vs non-US), and baseline BMI (<25 vs ≥25) as factors and baseline weight as covariate.	Baseline and 12 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has less than 24 weeks previous treatment with antipsychotics (cumulative; lifetime)
- Subject treated with aripiprazole can receive an additional 1 year of treatment at ≤5 mg/day, and this treatment will not be considered as part of the 24 weeks of previous treatment with antipsychotics
Has less than 4 years elapse since the initial onset of active-phase of symptoms
Has a body mass index (BMI) of <30 kg/m^2
Agrees to use an acceptable method of contraception for the duration of the study and for 30 days after the last dose of study drug
Subject meets the criteria for a primary diagnosis of schizophrenia, schizophreniform disorder, or bipolar I disorder
For bipolar I disorder, must have been experiencing an episode of acute mania within ≤14 days prior to Visit 1
Suitable for outpatient treatment
Additional criteria may apply

Exclusion Criteria:

Poses a current suicide risk
Has a history of poor or inadequate response to treatment with olanzapine
Has previously been treated with long-acting injectable antipsychotic medication within the 2 months prior to screening, or has > 6 months cumulative life use, or has received treatment with electroconvulsive therapy in their lifetime
Has initiated treatment with mood stabilizers (eg lithium, valproate, etc) >2 months prior to Visit 1
Has a positive drug screen for opioids, phencyclidine (PCP), amphetamine/methamphetamine, or cocaine
Has taken opioid agonists (eg, codeine, oxycodone, tramadol, morphine) within the 14 days prior to Visit 1, or has taken opioid antagonists, including naltrexone and naloxone, within 60 days prior to Visit 1
Taking any weight loss agents or hypoglycemic agents
Has a clinically significant or unstable medical illness, condition, or disorder that would be anticipated to potentially compromise subject safety or adversely affect the evaluation of efficacy
Has joined a weight management program or had significant changes in diet or exercise regimen within the past 6 weeks
Has started a smoking cessation program within the past 6 months
Has a history of diabetes
Currently pregnant or breastfeeding or is planning to become pregnant during the study or within 30 days of the last study drug administration
Additional criteria may apply

Contacts/Locations Module

Name	Affiliation	Role
Alkermes Medical Director	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
36946605	Derived	Kahn RS, Kane JM, Correll CU, Arevalo C, Simmons A, Graham C, Yagoda S, Hu B, McDonnell D. Olanzapine/Samidorphan in Young Adults With Schizophrenia, Schizophreniform Disorder, or Bipolar I Disorder Who Are Early in Their Illness: Results of the Randomized, Controlled ENLIGHTEN-Early Study. J Clin Psychiatry. 2023 Mar 22;84(3):22m14674. doi: 10.4088/JCP.22m14674.

IPD Sharing Statement Module

Results Section

Participant Flow Module

ID	Title	Description
FG000	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing
FG001	Olanzapine	Coated bilayer tablet Olanzapine: Daily oral dosing

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document 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 19, 2019	Dec 14, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

The baseline analysis population includes all randomized subjects who received at least 1 dose of study drug

Arm/Group Information

ID	Title	Description
BG000	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing
BG001	Olanzapine	Coated bilayer tablet Olanzapine: Daily oral dosing
BG002	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
	OG0004.91± .597 OG0016.77± .596

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		ANCOVA		.012		Least Squares Mean Difference	-1.87			2-Sided	95	-3.33	-.41					Superiority

Secondary

Percentage of Subjects With ≥10% Weight Gain at Week 12

Percentage of weight gain is analyzed based on the subject's assessment status (≥10% vs <10%) at Week 12 using a logistic regression model including treatment group, diagnosis (schizophrenia/schizophreniform disorder vs bipolar I disorder), region (US vs non-US), and baseline BMI (<25 vs ≥25) as factors and baseline weight as covariate.

Posted

Number

Percentage of participants

Baseline and 12 weeks

ID	Title	Description
OG000	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing
OG001	Olanzapine	Coated bilayer tablet Olanzapine: Daily oral dosing

Units	Counts
Participants	OG000

Secondary

Percentage of Subjects With ≥7% Weight Gain at Week 12

Posted

Number

Percentage of participants

Baseline and 12 weeks

ID	Title	Description
OG000	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing
OG001	Olanzapine	Coated bilayer tablet Olanzapine: Daily oral dosing

Units	Counts
Participants	OG000

Secondary

Number of Participants Experiencing of Adverse Events (AEs)

The safety population included all subjects who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 16 weeks

ID	Title	Description
OG000	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing
OG001	Olanzapine	Coated bilayer tablet Olanzapine: Daily oral dosing

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Waist Circumference at Week 12

Posted

Least Squares Mean

Standard Error

Centimeters

Baseline and Week 12

ID	Title	Description
OG000	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing
OG001	Olanzapine	Coated bilayer tablet Olanzapine: Daily oral dosing

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score Within the ALKS 3831 Group at Week 12

Clinical Global Impression-Severity (CGI-S) Score is a 3-item, clinician-rated scale used to assess global illness severity, overall improvement from the start of treatment, and therapeutic response. It 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."

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline and Week 12

ID	Title	Description
OG000	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing

Units	Counts
Participants	OG000

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	ALKS 3831	Coated bilayer tablet ALKS 3831: Olanzapine + samidorphan, daily oral dosing	1	211	8	211	134	211
EG001	Olanzapine	Coated bilayer tablet Olanzapine: Daily oral dosing	0	215	8	215	136	215

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 24.0	Non-systematic Assessment	EG0001 affected211 at risk EG0012 affected215 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 24.0	Non-systematic Assessment	EG0001 affected211 at risk EG0012 affected215 at risk
Seizure	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 affected211 at risk EG0010 affected215 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 affected211 at risk EG0010 affected215 at risk
Anxiety	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected211 at risk EG0012 affected215 at risk
Varicella	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0001 affected211 at risk EG0010 affected215 at risk
Limb deformity	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 affected211 at risk EG0010 affected215 at risk
Schizophrenia	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 affected211 at risk EG0012 affected215 at risk
Bipolar I Disorder	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected211 at risk EG0011 affected215 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Weight Increased	Investigations	MedDRA 24.0	Non-systematic Assessment	EG00046 affected211 at risk EG00155 affected215 at risk
Somnolence	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG00023 affected211 at risk EG00120 affected215 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24.0	Non-systematic Assessment	EG00016 affected211 at risk EG00114 affected215 at risk
Headache	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG00013 affected211 at risk EG00110 affected215 at risk
Sedation	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG00011 affected211 at risk EG00113 affected215 at risk
Waist Circumference Increased	Investigations	MedDRA 24.0	Non-systematic Assessment	EG00010 affected211 at risk EG00115 affected215 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0009 affected211 at risk EG0015 affected215 at risk
Anxiety	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG0008 affected211 at risk EG00112 affected215 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 24.0	Non-systematic Assessment	EG0008 affected211 at risk EG0015 affected215 at risk
Fatigue	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0008 affected211 at risk EG0014 affected215 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24.0	Non-systematic Assessment	EG0007 affected211 at risk EG0018 affected215 at risk
Dizziness	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 affected211 at risk EG0013 affected215 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 affected211 at risk EG0011 affected215 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 affected211 at risk EG0019 affected215 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 affected211 at risk EG0011 affected215 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 affected211 at risk EG0012 affected215 at risk

ID	Term
D012559	Schizophrenia
D011618	Psychotic Disorders

ID	Term
D000077152	Olanzapine

ParticipantsBG002202

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