A Study of ALKS 3831 in Subjects With Schizophrenia and Alcohol Use Disorder

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02161718
• Collaborator: (none)
• Enrollment: 300
• Locations: 71
• Arms: 2
• Actual Duration (Months): 33.1
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This double-blind, randomized study will evaluate the efficacy, safety and tolerability of ALKS 3831 in subjects with schizophrenia and alcohol use disorder (AUD).

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Alcohol Use Disorder	Drug: Samidorphan + olanzapine (ALKS 3831); Drug: Placebo + olanzapine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Efficacy, Safety and Tolerability Study of ALKS 3831 in Schizophrenia With Alcohol Use Disorder
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: Jan 11, 2017
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Samidorphan + olanzapine (ALKS 3831) Active study drug	Drug: Samidorphan + olanzapine (ALKS 3831); Oral tablet, taken once daily
Placebo Comparator: Placebo + olanzapine	Drug: Placebo + olanzapine; Oral tablet, taken once daily

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Independent Adjudication Committee (IAC) Adjudicated Event of Exacerbation of Disease (EEDS) [Up to 15 months]

   EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC): Hospitalization (includes psychiatric& treatment of alcohol intoxication/withdrawal) >= 25% or >= 15 point increase from randomization in PANSS total score PANSS items score of P1, P2, P3, P6, P7 or G8 that meets 1 of the following: 3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease

Secondary Outcome Measures

1. Number of Events of Exacerbation of Disease (EEDS) [Up to 15 months]

   EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC): Hospitalization(includes psychiatric & treatment of alcohol intoxication/withdrawal) >= 25% or >= 15 point increase from randomization in PANSS total score PANSS items score of P1, P2, P3, P6, P7 or G8 that meets 1 of the following: 3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease

2. Number and Percentage of Subjects With at Least 1 Level Decrease in World Health Organization (WHO) Drinking Risk Level From Baseline to Week 24 of the Double-blind Treatment (Study Week 27) [24 weeks]

   Alcohol consumption per day = (total number of drinks x 14 gram) / (total number of days) WHO criteria for risk of alcohol consumption on a single drinking day: Abstinence- Males: 0 g; Females- 0 g Low Risk- Males: 1-40 g; Females: 1-20 g Medium Risk- Males: 41- 60 g; Females: 21- 40 g High Risk- Males: 61-100 g; Females: 41-60 g Very High Risk- Males: >= 101 g; Females: >= 61 g

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has a BMI between 18.0 and 40.0 kg/m2, inclusive

• Has a diagnosis of schizophrenia

• Has a diagnosis of alcohol use disorder (AUD)

• Has experienced an acute exacerbation of schizophrenia within the past 6 months

• Additional criteria may apply

Exclusion Criteria:

• Is pregnant or breastfeeding

• Had first lifetime psychotic episode less than 1 year before screening or has experienced only a single lifetime psychotic episode

• Has a known or suspected intolerance, allergy, or hypersensitivity to olanzapine

• Has current or pending legal charges with the potential for incarceration

• Has a positive drug screen for opiates

• 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	Culver City	California	United States	90230
5	Alkermes Investigational Site	Garden Grove	California	United States	92845
6	Alkermes Investigational Site	Irvine	California	United States	92617
7	Alkermes Investigational Site	La Jolla	California	United States	92037
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	San Diego	California	United States	92123
14	Alkermes Investigational Site	San Francisco	California	United States	94121
15	Alkermes Investigational Site	Torrance	California	United States	90502
16	Alkermes Investigational Site	Washington	District of Columbia	United States	20016
17	Alkermes Investigational Site	Fort Lauderdale	Florida	United States	33308
18	Alkermes Investigational Site	Leesburg	Florida	United States	34748
19	Alkermes Investigational Site	Maitland	Florida	United States	32751
20	Alkermes Investigational Site	Miami	Florida	United States	33122
21	Alkermes Investigational Site	Miami	Florida	United States	33136
22	Alkermes Investigational Site	North Miami	Florida	United States	33021
23	Alkermes Investigational Site	Oakland Park	Florida	United States	33334
24	Alkermes Investigational Site	Orlando	Florida	United States	32803
25	Alkermes Investigational Site	Tampa	Florida	United States	33613
26	Alkermes Investigational Site	Atlanta	Georgia	United States	30308
27	Alkermes Investigational Site	Augusta	Georgia	United States	30912
28	Alkermes Investigational Site	Decatur	Georgia	United States	30030
29	Alkermes Investigational Site	Chicago	Illinois	United States	60640
30	Alkermes Investigational Site	Hoffman Estates	Illinois	United States	60169
31	Alkermes Investigational Site	Oak Brook	Illinois	United States	60523
32	Alkermes Investigational Site	Shreveport	Louisiana	United States	71101
33	Alkermes Investigational Site	Worcester	Massachusetts	United States	01605
34	Alkermes Investigational Site	Flowood	Mississippi	United States	39232
35	Alkermes Investigational Site	Creve Coeur	Missouri	United States	63141
36	Alkermes Investigational Site	Kansas City	Missouri	United States	64108
37	Alkermes Investigational Site	Saint Louis	Missouri	United States	63118
38	Alkermes Investigational Site	Las Vegas	Nevada	United States	89102
39	Alkermes Investigational Site	Claremont	New Hampshire	United States	03743
40	Alkermes Investigational Site	Nashua	New Hampshire	United States	03060
41	Alkermes Investigational Site	Neptune	New Jersey	United States	07753
42	Alkermes Investigational Site	Cedarhurst	New York	United States	11516
43	Alkermes Investigational Site	Jamaica	New York	United States	11423
44	Alkermes Investigational Site	New York	New York	United States	10021
45	Alkermes Investigational Site	New York	New York	United States	10032
46	Alkermes Investigational Site	New York	New York	United States	10035
47	Alkermes Investigational Site	Rochester	New York	United States	14642
48	Alkermes Investigational Site	Staten Island	New York	United States	10312
49	Alkermes Investigational Site	Dayton	Ohio	United States	45417
50	Alkermes Investigational Site	Oklahoma City	Oklahoma	United States	73112
51	Alkermes Investigational Site	Scranton	Pennsylvania	United States	18503
52	Alkermes Investigational Site	Charleston	South Carolina	United States	29401
53	Alkermes Investigational Site	Charleston	South Carolina	United States	29407
54	Alkermes Investigational Site	Charleston	South Carolina	United States	29425
55	Alkermes Investigational Site	Austin	Texas	United States	78754
56	Alkermes Investigational Site	Dallas	Texas	United States	75214
57	Alkermes Investigational Site	DeSoto	Texas	United States	75115
58	Alkermes Investigational Site	Bellevue	Washington	United States	98007
59	Alkermes Investigational Site	Burgas		Bulgaria	8000
60	Alkermes Investigational Site	Kazanlak		Bulgaria	6100
61	Alkermes Investigational Site	Lovech		Bulgaria	5500
62	Alkermes Investigational Site	Novi Iskar		Bulgaria	1282
63	Alkermes Investigational Site	Sofia		Bulgaria	1606
64	Alkermes Investigational Site	Tserova Koria		Bulgaria	8260
65	Alkermes Investigational Site	Varna		Bulgaria	9002
66	Alkermes Investigational Site	Varna		Bulgaria	9020
67	Alkermes Investigational Site	Vratsa		Bulgaria	3000
68	Alkermes Investigational Site	Belchatow		Poland	97-400
69	Alkermes Investigational Site	Bialystok		Poland	15-464
70	Alkermes Investigational Site	Gdansk		Poland	80-546
71	Alkermes Investigational Site	Lublin		Poland	20-109

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

• Study Director: David McDonnell, MD, Alkermes, Inc.

Study Documents (Full-Text)

• Study Protocol - Mar 1, 2016
• Statistical Analysis Plan - Jan 20, 2017

More Information

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT02161718
• Other Study ID Numbers: ALK3831-401
• First Posted: Jun 12, 2014
• Last Update Posted: Oct 8, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Alkermes, Inc.: Alkermes; Schizophrenia; Alcohol Use Disorder; ALKS 3831
• Additional relevant MeSH terms: Disease; Alcoholism; Schizophrenia; Alcohol Drinking; Olanzapine

Study Results

Participant Flow

Recruitment Details

Subjects were adults with a diagnosis of schizophrenia and Alcohol Use Disorder (AUD). Subjects must also have recently experienced an exacerbation of disease symptoms (eg, hospitalization), but could not exceed a pre-defined level of symptom severity at the time of screening (as measured by assessments like the Positive and Negative Symptom Scale [PANSS] and Clinical Global Impression- Severity [CGI-S]).

Pre-assignment Detail

After screening, subjects began a 4-week open-label olanzapine dosing period followed by a 2- week open-label ALKS 3831 period. Subjects who did not tolerate ALKS 3831 during the second open-label period were discontinued from the study prior to randomization. A total of 300 subjects were enrolled in the study, and 255 completed the open-label olanzapine period. 234 subjects were randomized following the open-label ALKS 3831 period, however, 5 subjects discontinued prior to receiving treatment.

Arm/Group Title	Open-label ALKS 3831	ALKS 3831	Olanzapine + Placebo
Arm/Group Description	Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg)	Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg)	Oral tablet, taken once daily Olanzapine dose level determined by investigator
Period Title: Open-Label ALKS 3831 Period
STARTED	255	0	0
COMPLETED	234	0	0
NOT COMPLETED	21	0	0
Period Title: Open-Label ALKS 3831 Period
STARTED	0	112	117
COMPLETED	0	53	58
NOT COMPLETED	0	59	59

Baseline Characteristics

Arm/Group Title	ALKS 3831	Olanzapine + Placebo	Total
Arm/Group Description	Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg)	Oral tablet, taken once daily Olanzapine dose level determined by investigator	Total of all reporting groups
Overall Participants	112	117	229
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.4 (10.60)	45.1 (10.22)	45.7 (10.40)
Sex: Female, Male (Count of Participants)
Female	23 20.5%	26 22.2%	49 21.4%
Male	89 79.5%	91 77.8%	180 78.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 3.6%	7 6%	11 4.8%
Not Hispanic or Latino	108 96.4%	109 93.2%	217 94.8%
Unknown or Not Reported	0 0%	1 0.9%	1 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 1.8%	1 0.9%	3 1.3%
Native Hawaiian or Other Pacific Islander	2 1.8%	0 0%	2 0.9%
Black or African American	65 58%	57 48.7%	122 53.3%
White	43 38.4%	58 49.6%	101 44.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 0.9%	1 0.4%
Region of Enrollment (participants) [Number]
United States	85 75.9%	76 65%	161 70.3%
Bulgaria	24 21.4%	36 30.8%	60 26.2%
Poland	3 2.7%	5 4.3%	8 3.5%
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	173.4 (9.6)	174.4 (8.4)	173.9 (9.0)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	86.2 (19.7)	86.8 (18.1)	86.5 (18.9)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.6 (5.7)	28.5 (5.4)	28.6 (5.6)
Body Mass Index (BMI) Group (Count of Participants)
Underweight (<18.5)	3 2.7%	0 0%	3 1.3%
Normal (18.5 to <25)	34 30.4%	29 24.8%	63 27.5%
Overweight (25 to <30)	33 29.5%	49 41.9%	82 35.8%
Obese (>= 30)	42 37.5%	39 33.3%	81 35.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Independent Adjudication Committee (IAC) Adjudicated Event of Exacerbation of Disease (EEDS)
Description	EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC): Hospitalization (includes psychiatric& treatment of alcohol intoxication/withdrawal) >= 25% or >= 15 point increase from randomization in PANSS total score PANSS items score of P1, P2, P3, P6, P7 or G8 that meets 1 of the following: 3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease
Time Frame	Up to 15 months

Outcome Measure Data

Analysis Population Description

Efficacy analyses were carried out using the intent to treat (ITT) population, i.e. all randomized subjects who received at least one dose of study drug post-randomization

Arm/Group Title	ALKS 3831	Olanzapine + Placebo
Arm/Group Description	Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg)	Oral tablet, taken once daily Olanzapine dose level determined by investigator
Measure Participants	112	117
Number of Subjects with IAC Adjudicated EEDS	25 22.3%	29 24.8%
Number of Subjects Censored	87 77.7%	88 75.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALKS 3831, Olanzapine + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.746
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.251
	Estimation Comments

2. Secondary Outcome

Title	Number of Events of Exacerbation of Disease (EEDS)
Description	EEDS was defined as any of the following occurring during the double-blind period & was related to worsening of disease symptoms, as confirmed by the Independent Adjudication Committee (IAC): Hospitalization(includes psychiatric & treatment of alcohol intoxication/withdrawal) >= 25% or >= 15 point increase from randomization in PANSS total score PANSS items score of P1, P2, P3, P6, P7 or G8 that meets 1 of the following: 3a. Score >= 5 for subjects at a 2nd ad hoc visit with a score <=3 at randomization 3b. Score >= 6 for subjects at a 2nd ad hoc visit with a score =4 at randomization 4. Engagement in self injury, aggressive behavior, or suicidal/homicidal ideation 5. Initiation of rescue medication, including increase in olanzapine dosage initially prescribed at randomization 6. ER visit 7. Subject withdraws or PI discontinues subject for lack of efficacy, lost to follow-up, or withdrawal by subject 8. Arrest or incarceration related to subject's underlying disease
Time Frame	Up to 15 months

Outcome Measure Data

Analysis Population Description

Efficacy analyses were carried out using the intent to treat (ITT) population, i.e. all randomized subjects who received at least one dose of study drug post-randomization

Arm/Group Title	ALKS 3831	Olanzapine + Placebo
Arm/Group Description	Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg)	Oral tablet, taken once daily Olanzapine dose level determined by investigator
Measure Participants	112	117
Number [Events]	35	49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALKS 3831, Olanzapine + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.372
	Comments
	Method	Andersen-Gill Recurrent-Event Cox Model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.43 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number and Percentage of Subjects With at Least 1 Level Decrease in World Health Organization (WHO) Drinking Risk Level From Baseline to Week 24 of the Double-blind Treatment (Study Week 27)
Description	Alcohol consumption per day = (total number of drinks x 14 gram) / (total number of days) WHO criteria for risk of alcohol consumption on a single drinking day: Abstinence- Males: 0 g; Females- 0 g Low Risk- Males: 1-40 g; Females: 1-20 g Medium Risk- Males: 41- 60 g; Females: 21- 40 g High Risk- Males: 61-100 g; Females: 41-60 g Very High Risk- Males: >= 101 g; Females: >= 61 g
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Efficacy analyses were carried out using subjects from the intent to treat (ITT) population with postbaseline data on drinking habits.

Arm/Group Title	ALKS 3831	Olanzapine + Placebo
Arm/Group Description	Oral tablet, taken once daily ALKS 3831: Olanzapine (dose level determined by investigator) + Samidorphan (10mg)	Oral tablet, taken once daily Olanzapine dose level determined by investigator
Measure Participants	111	116
>= 1 Level Decrease from Baseline	45 40.2%	44 37.6%
< 1 Level Decrease from Baseline	66 58.9%	72 61.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALKS 3831, Olanzapine + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.963
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events are presented for the randomized, double-blind period (9-15 months) as well as the 2 week open-label ALKS 3831 (olanzapine + samidorphan) period for a total timeframe of up to 62 weeks.
Arm/Group Title	Open- Label ALKS 3831		Olanzapine + Placebo		ALKS 3831
Arm/Group Description	A 2-week open-label period; all subjects received olanzapine (dose determined by investigator) + 10 mg samidorphan		All randomized subjects who received at least 1 dose of study drug (olanzapine + placebo) during the double-blind treatment period		All randomized subjects who received at least 1 dose of ALKS 3831 (olanzapine + samidorphan) during the double-blind treatment period.
All Cause Mortality
	Open- Label ALKS 3831		Olanzapine + Placebo		ALKS 3831
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/255 (0%)		1/117 (0.9%)		1/112 (0.9%)
Serious Adverse Events
	Open- Label ALKS 3831		Olanzapine + Placebo		ALKS 3831
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/255 (1.6%)		12/117 (10.3%)		7/112 (6.3%)
Infections and infestations
Parotitis	0/255 (0%)		1/117 (0.9%)		0/112 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	0/255 (0%)		1/117 (0.9%)		0/112 (0%)
Fall	1/255 (0.4%)		0/117 (0%)		0/112 (0%)
Laceration	1/255 (0.4%)		0/117 (0%)		0/112 (0%)
Investigations
Electrocardiogram abnormal	0/255 (0%)		0/117 (0%)		1/112 (0.9%)
Nervous system disorders
Convulsion	1/255 (0.4%)		0/117 (0%)		0/112 (0%)
Dizziness	1/255 (0.4%)		0/117 (0%)		0/112 (0%)
Transient ischaemic attack	0/255 (0%)		0/117 (0%)		1/112 (0.9%)
Psychiatric disorders
Alcoholism	1/255 (0.4%)		0/117 (0%)		0/112 (0%)
Schizophrenia, paranoid type	1/255 (0.4%)		0/117 (0%)		0/112 (0%)
Schizophrenia	0/255 (0%)		4/117 (3.4%)		3/112 (2.7%)
Paranoia	0/255 (0%)		0/117 (0%)		1/112 (0.9%)
Psychotic disorder	0/255 (0%)		0/117 (0%)		1/112 (0.9%)
Aggression	0/255 (0%)		1/117 (0.9%)		0/112 (0%)
Agitation	0/255 (0%)		1/117 (0.9%)		0/112 (0%)
Disturbance in social behavior	0/255 (0%)		2/117 (1.7%)		0/112 (0%)
Suicidal ideation	0/255 (0%)		3/117 (2.6%)		0/112 (0%)
Renal and urinary disorders
Chronic obstructive pulmonary disease	0/255 (0%)		0/117 (0%)		1/112 (0.9%)
Other (Not Including Serious) Adverse Events
	Open- Label ALKS 3831		Olanzapine + Placebo		ALKS 3831
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/255 (0%)		19/117 (16.2%)		26/112 (23.2%)
Infections and infestations
Nasopharyngitis	0/255 (0%)		5/117 (4.3%)		7/112 (6.3%)
Investigations
Weight increased	0/255 (0%)		14/117 (12%)		16/112 (14.3%)
Alanine aminotransferase increased	0/255 (0%)		0/117 (0%)		6/112 (5.4%)

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