A Study of ALKS 3831 in Adults With Schizophrenia (The ENLIGHTEN-2 Study)

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02694328
• Collaborator: (none)
• Enrollment: 561
• Locations: 54
• Arms: 2
• Actual Duration (Months): 32.2
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will evaluate weight gain of ALKS 3831 compared to olanzapine in adult subjects with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: ALKS 3831; Drug: Olanzapine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 561 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study to Evaluate Weight Gain of ALKS 3831 Compared to Olanzapine in Adults With Schizophrenia
• Actual Study Start Date: Mar 2, 2016
• Actual Primary Completion Date: Nov 7, 2018
• Actual Study Completion Date: Nov 7, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALKS 3831 Administered as a coated bilayer tablet	Drug: ALKS 3831; Daily dosing
Active Comparator: Olanzapine Administered as a coated bilayer tablet	Drug: Olanzapine; Daily dosing

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Body Weight at Week 24 [Baseline and Week 24]

2. Percentage of Participants With >/= 10% Weight Gain at Week 24 [Baseline and Week 24]

Secondary Outcome Measures

1. Percentage of Participants With >/= 7% Weight Gain at Week 24 [Baseline and Week 24]

2. Number of Participants Experiencing of Adverse Events (AEs) [24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject has a body mass index (BMI) of 18.0-30.0 kg/m^2, inclusive, at Visit 1 and Visit 2

• Subject meets the DSM-5 criteria for a primary diagnosis of schizophrenia

• Subject is appropriate for outpatient treatment; has no hospitalizations for acute exacerbations of schizophrenia within 6 months before Visit 1

• Subject has maintained a stable body weight (change </= 5%) for at least 3 months prior to Visit 1 based on self-report

• Additional criteria may apply

Exclusion Criteria:

• Subject has any of the following psychiatric conditions per DSM-5 criteria:

• Diagnosis of schizoaffective disorder or bipolar I or II disorder, or current, untreated or unstable major depressive disorder

• Clinically significant cognitive difficulties present within the past 2 years that could interfere with participation in the study

• Drug-induced or toxic psychosis

• Any other psychiatric condition that could interfere with participation in the study

• Subject poses a current suicide risk at Visit 1 or Visit 2 in the opinion of the investigator

• Subject has inflammatory bowel disease or any other gastrointestinal disorder associated with weight loss, anorexia nervosa, or binge eating disorder

• Additional criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alkermes Investigational Site	Little Rock	Arkansas	United States	72211
2	Alkermes Investigational Site	Springdale	Arkansas	United States	72764
3	Alkermes Investigational Site	Anaheim	California	United States	92805
4	Alkermes Investigational Site	Cerritos	California	United States	90703
5	Alkermes Investigational Site	Culver City	California	United States	90230
6	Alkermes Investigational Site	Garden Grove	California	United States	92845
7	Alkermes Investigational Site	Glendale	California	United States	91206
8	Alkermes Investigational Site	Long Beach	California	United States	90822
9	Alkermes Investigational Site	National City	California	United States	91950
10	Alkermes Investigational Site	Oakland	California	United States	94612
11	Alkermes Investigational Site	Oceanside	California	United States	92056
12	Alkermes Investigational Site	Orange	California	United States	92868
13	Alkermes Investigational Site	Pico Rivera	California	United States	90660
14	Alkermes Investigational Site	Redlands	California	United States	92374
15	Alkermes Investigational Site	San Diego	California	United States	92103
16	Alkermes Investigational Site	San Diego	California	United States	92123
17	Alkermes Investigational Site	Temecula	California	United States	92591
18	Alkermes Investigational Site	Torrance	California	United States	90502
19	Alkermes Investigational Site	Washington	District of Columbia	United States	20016
20	Alkermes Investigational Site	Lauderhill	Florida	United States	33319
21	Alkermes Investigational Site	Miami	Florida	United States	33136
22	Alkermes Investigational Site	North Miami	Florida	United States	33161
23	Alkermes Investigational Site	Oakland Park	Florida	United States	33334
24	Alkermes Investigational Site	Tampa	Florida	United States	33609
25	Alkermes Investigational Site	Atlanta	Georgia	United States	30329
26	Alkermes Investigational Site	Augusta	Georgia	United States	30912
27	Alkermes Investigational Site	Decatur	Georgia	United States	30030
28	Alkermes Investigational Site	Chicago	Illinois	United States	60640
29	Alkermes Investigational Site	Grand Rapids	Michigan	United States	49503
30	Alkermes Investigational Site	Flowood	Mississippi	United States	39232
31	Alkermes Investigational Site	Creve Coeur	Missouri	United States	63141
32	Alkermes Investigational Site	O'Fallon	Missouri	United States	63368
33	Alkermes Investigational Site	Saint Louis	Missouri	United States	63128
34	Alkermes Investigational Site	Las Vegas	Nevada	United States	89102
35	Alkermes Investigational Site	Berlin	New Jersey	United States	08009
36	Alkermes Investigational Site	Marlton	New Jersey	United States	08053
37	Alkermes Investigational Site	Brooklyn	New York	United States	11235
38	Alkermes Investigational Site	Jamaica	New York	United States	11432
39	Alkermes Investigational Site	New York	New York	United States	10032
40	Alkermes Investigational Site	New York	New York	United States	10035
41	Alkermes Investigational Site	Rochester	New York	United States	14615
42	Alkermes Investigational Site	Wards Island	New York	United States	10035
43	Alkermes Investigational Site	Canton	Ohio	United States	44718
44	Alkermes Investigational Site	Dayton	Ohio	United States	45417
45	Alkermes Investigational Site	Middleburg Heights	Ohio	United States	44130
46	Alkermes Investigational Site	Allentown	Pennsylvania	United States	18104
47	Alkermes Investigational Site	Austin	Texas	United States	78754
48	Alkermes Investigational Site	Austin	Texas	United States	78759
49	Alkermes Investigational Site	Dallas	Texas	United States	75243
50	Alkermes Investigational Site	DeSoto	Texas	United States	75115
51	Alkermes Investigational Site	Houston	Texas	United States	77030
52	Alkermes Investigational Site	Bellevue	Washington	United States	98007
53	Alkermes Investigational Site	San Juan		Puerto Rico	00918
54	Alkermes Investigational Site	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

• Study Director: Alkermes Medical Director, Alkermes, Inc.

Study Documents (Full-Text)

• Study Protocol - Sep 18, 2018
• Statistical Analysis Plan - Sep 18, 2018

More Information

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT02694328
• Other Study ID Numbers: ALK3831-A303
• First Posted: Feb 29, 2016
• Last Update Posted: Feb 10, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Alkermes, Inc.: Alkermes; ALKS 3831; Samidorphan; Schizophrenia; Olanzapine; Weight
• Additional relevant MeSH terms: Schizophrenia; Olanzapine

Study Results

Participant Flow

Arm/Group Title	Olanzapine	ALKS 3831
Arm/Group Description	Administered as a coated bilayer tablet Olanzapine: Daily dosing	Administered as a coated bilayer tablet ALKS 3831: Daily dosing
Period Title: Overall Study
STARTED	276	274
COMPLETED	176	176
NOT COMPLETED	100	98

Baseline Characteristics

Arm/Group Title	Olanzapine	ALKS 3831	Total
Arm/Group Description	Administered as a coated bilayer tablet Olanzapine: Daily dosing	Administered as a coated bilayer tablet ALKS 3831: Daily dosing	Total of all reporting groups
Overall Participants	276	274	550
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.1 (10.01)	40.3 (9.79)	40.2 (9.90)
Sex: Female, Male (Count of Participants)
Female	69 25%	81 29.6%	150 27.3%
Male	207 75%	193 70.4%	400 72.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	42 15.2%	37 13.5%	79 14.4%
Not Hispanic or Latino	234 84.8%	237 86.5%	471 85.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.7%	2 0.7%	4 0.7%
Asian	4 1.4%	4 1.5%	8 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	1 0.2%
Black or African American	193 69.9%	199 72.6%	392 71.3%
White	65 23.6%	63 23%	128 23.3%
More than one race	8 2.9%	3 1.1%	11 2%
Unknown or Not Reported	4 1.4%	2 0.7%	6 1.1%
Region of Enrollment (participants) [Number]
United States	276 100%	274 100%	550 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Body Weight at Week 24
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) population includes all randomized subjects who received at least 1 dose of study drug and had at least 1 postbaseline weight assessment

Arm/Group Title	Olanzapine	ALKS 3831
Arm/Group Description	Administered as a coated bilayer tablet Olanzapine: Daily dosing	Administered as a coated bilayer tablet ALKS 3831: Daily dosing
Measure Participants	272	266
Least Squares Mean (Standard Error) [Percent change in body weight]	6.59 (0.668)	4.21 (0.681)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALKS 3831
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	P-value was adjusted using the Cui, Hung, and Wang (CHW) method to account for the unblinded interim analysis for sample size re-estimation.
	Method	ANCOVA
	Comments	Missing values at Week 24 were imputed using multiple imputation.
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.38
	Confidence Interval	(2-Sided) 95%; -3.88 to -0.88
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.765
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With >/= 10% Weight Gain at Week 24
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The FAS population included all randomized subjects who received at least 1 dose of study drug and had at least 1 postbaseline weight assessment.

Arm/Group Title	Olanzapine	ALKS 3831
Arm/Group Description	Administered as a coated bilayer tablet Olanzapine: Daily dosing	Administered as a coated bilayer tablet ALKS 3831: Daily dosing
Measure Participants	272	266
Number [Percentage of participants]	29.8 10.8%	17.8 6.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olanzapine, ALKS 3831
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	P-value was adjusted using the CHW method to account for the unblinded interim analysis for sample size re-estimation.
	Method	Regression, Logistic
	Comments	Missing values at Week 24 were imputed using multiple imputation.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-13.7
	Confidence Interval	(2-Sided) 95%; -22.8 to -4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference (RD) of ALKS 3831 vs. Olanzapine

3. Secondary Outcome

Title	Percentage of Participants With >/= 7% Weight Gain at Week 24
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The FAS population included all randomized subjects who received at least 1 dose of study drug and had at least 1 postbaseline weight assessment.

Arm/Group Title	Olanzapine	ALKS 3831
Arm/Group Description	Administered as a coated bilayer tablet Olanzapine: Daily dosing	Administered as a coated bilayer tablet ALKS 3831: Daily dosing
Measure Participants	272	266
Number [Percentage of participants]	42.7 15.5%	27.5 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olanzapine, ALKS 3831
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Regression, Logistic
	Comments	Missing values at Week 24 were imputed using multiple imputation.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-15.9
	Confidence Interval	(2-Sided) 95%; -25.3 to -6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference (RD) ALKS 3831 vs. Olanzapine

4. Secondary Outcome

Title	Number of Participants Experiencing of Adverse Events (AEs)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The Safety Population includes all randomized subjects who received at least 1 dose of study drug.

Arm/Group Title	Olanzapine	ALKS 3831
Arm/Group Description	Administered as a coated bilayer tablet Olanzapine: Daily dosing	Administered as a coated bilayer tablet ALKS 3831: Daily dosing
Measure Participants	276	274
Count of Participants [Participants]	227 82.2%	203 74.1%

Adverse Events

Time Frame	Up to 24 weeks
Arm/Group Title	Olanzapine		ALKS 3831
Arm/Group Description	Administered as a coated bilayer tablet Olanzapine: Daily dosing		Administered as a coated bilayer tablet ALKS 3831: Daily dosing
All Cause Mortality
	Olanzapine		ALKS 3831
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/276 (0%)		0/274 (0%)
Serious Adverse Events
	Olanzapine		ALKS 3831
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/276 (2.5%)		10/274 (3.6%)
Cardiac disorders
Tachycardia	0/276 (0%)	0	1/274 (0.4%)	1
Gastrointestinal disorders
Rectal haemorrhage	0/276 (0%)	0	1/274 (0.4%)	1
Infections and infestations
Gastroenteritis	0/276 (0%)	0	1/274 (0.4%)	1
Influenza	0/276 (0%)	0	1/274 (0.4%)	1
Abdominal wall abscess	1/276 (0.4%)	1	0/274 (0%)	0
Cellulitis staphylococcal	1/276 (0.4%)	1	0/274 (0%)	0
Infectious colitis	1/276 (0.4%)	1	0/274 (0%)	0
Injury, poisoning and procedural complications
Pelvic fracture	0/276 (0%)	0	1/274 (0.4%)	1
Road traffic accident	1/276 (0.4%)	1	0/274 (0%)	0
Nervous system disorders
Sedation	0/276 (0%)	0	1/274 (0.4%)	1
Depressed level of consciousness	1/276 (0.4%)	1	0/274 (0%)	0
Psychiatric disorders
Schizophrenia	3/276 (1.1%)	3	1/274 (0.4%)	1
Substance abuse	0/276 (0%)	0	1/274 (0.4%)	1
Substance-induced psychotic disorder	0/276 (0%)	0	1/274 (0.4%)	1
Suicidal ideation	0/276 (0%)	0	1/274 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/276 (0%)	0	1/274 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Olanzapine		ALKS 3831
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	159/276 (57.6%)		146/274 (53.3%)
Gastrointestinal disorders
Dry mouth	22/276 (8%)	22	35/274 (12.8%)	36
Injury, poisoning and procedural complications
Extra dose administered	17/276 (6.2%)	29	14/274 (5.1%)	18
Investigations
Weight increased	100/276 (36.2%)	102	68/274 (24.8%)	68
Waist circumference increased	22/276 (8%)	22	17/274 (6.2%)	17
Blood creatine phosphokinase increased	12/276 (4.3%)	15	14/274 (5.1%)	16
Metabolism and nutrition disorders
Increased appetite	34/276 (12.3%)	35	30/274 (10.9%)	30
Nervous system disorders
Somnolence	50/276 (18.1%)	57	58/274 (21.2%)	63

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.