A Phase 3, Long-term Safety and Tolerability Study of ALKS 3831 in Adults With Schizophrenia

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02873208
• Collaborator: (none)
• Enrollment: 266
• Locations: 45
• Arm: 1
• Actual Duration (Months): 38.3
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the long-term safety and tolerability of ALKS 3831 in subjects with schizophrenia.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 266 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter Study to Assess the Long Term Safety and Tolerability of ALKS 3831 in Subjects With Schizophrenia
• Actual Study Start Date: Aug 7, 2016
• Actual Primary Completion Date: Oct 17, 2019
• Actual Study Completion Date: Oct 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALKS 3831 Oral tablet, daily dosing	Drug: ALKS 3831; Coated bilayer tablet containing 10 mg, 15 mg or 20 mg olanzapine and 10 mg samidorphan

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Adverse Events [Up to 52 weeks]

   Overall summary of treatment emergent adverse events during the treatment period

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Agrees to use an acceptable method of contraception for the duration of the study

• Subject has completed the 24-week treatment period in the antecedent study, ALK3831-A303, within 7 days

• Additional criteria may apply

Exclusion Criteria:

• Subject is currently taking medications that are contraindicated with olanzapine use or exhibit drug-interaction potential with olanzapine

• Subject has a positive test for drugs of abuse at study entry

• Subject is pregnant, planning to become pregnant, or breastfeeding during the study

• 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	Lemon Grove	California	United States	91945
9	Alkermes Investigational Site	Long Beach	California	United States	90822
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	Hollywood	Florida	United States	33024
20	Alkermes Investigational Site	Lauderhill	Florida	United States	33319
21	Alkermes Investigational Site	North Miami	Florida	United States	33161
22	Alkermes Investigational Site	Atlanta	Georgia	United States	30329
23	Alkermes Investigational Site	Augusta	Georgia	United States	30912
24	Alkermes Investigational Site	Decatur	Georgia	United States	30030
25	Alkermes Investigational Site	Chicago	Illinois	United States	60640
26	Alkermes Investigational Site	Grand Rapids	Michigan	United States	49503
27	Alkermes Investigational Site	Flowood	Mississippi	United States	39232
28	Alkermes Investigational Site	Creve Coeur	Missouri	United States	63141
29	Alkermes Investigational Site	Saint Louis	Missouri	United States	63128
30	Alkermes Investigational Site	Las Vegas	Nevada	United States	89102
31	Alkermes Investigational Site	Berlin	New Jersey	United States	08009
32	Alkermes Investigational Site	Marlton	New Jersey	United States	08053
33	Alkermes Investigational Site	Brooklyn	New York	United States	11235
34	Alkermes Investigational Site	Jamaica	New York	United States	11432
35	Alkermes Investigational Site	Rochester	New York	United States	14615
36	Alkermes Investigational Site	Canton	Ohio	United States	44718
37	Alkermes Investigational Site	Dayton	Ohio	United States	45417
38	Alkermes Investigational Site	Austin	Texas	United States	78754
39	Alkermes Investigational Site	Austin	Texas	United States	78759
40	Alkermes Investigational Site	Dallas	Texas	United States	75243
41	Alkermes Investigational Site	DeSoto	Texas	United States	75115
42	Alkermes Investigational Site	Houston	Texas	United States	77030
43	Alkermes Investigational Site	Bellevue	Washington	United States	98007
44	Alkermes Investigational Site	San Juan		Puerto Rico	00918
45	Alkermes Investigational Site	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

• Principal Investigator: Alkermes Medical Director, Alkermes, Inc.

Study Documents (Full-Text)

• Study Protocol - Apr 26, 2018
• Statistical Analysis Plan - Jun 11, 2019

More Information

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT02873208
• Other Study ID Numbers: ALK3831-A304
• First Posted: Aug 19, 2016
• Last Update Posted: Jul 21, 2021
• Last Verified: Jul 1, 2021

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

Study Results

Participant Flow

Recruitment Details	Subjects that had completed the 24-week treatment period of the antecedent study ALK3831-A303 within seven days prior to enrollment were eligible to be enrolled in the study.
Pre-assignment Detail	One patient was enrolled and not dosed. A total of 265 patients were administered at least one dose of ALKS 3831 and included in the safety population.

Arm/Group Title	ALKS 3831
Arm/Group Description	All subjects assigned to ALKS 3831 ALKS 3831: Coated bilayer tablet containing 10 mg, 15 mg or 20 mg olanzapine and 10 mg samidorphan Oral tablet, daily dosing
Period Title: Overall Study
STARTED	265
COMPLETED	167
NOT COMPLETED	98

Baseline Characteristics

Arm/Group Title	ALKS 3831
Arm/Group Description	All subjects assigned to ALKS 3831 ALKS 3831: Coated bilayer tablet containing 10 mg, 15 mg or 20 mg olanzapine and 10 mg samidorphan Oral tablet, daily dosing
Overall Participants	265
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.7 (9.74)
Sex: Female, Male (Count of Participants)
Female	73 27.5%
Male	192 72.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	40 15.1%
Not Hispanic or Latino	225 84.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 0.8%
Asian	3 1.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	187 70.6%
White	64 24.2%
More than one race	6 2.3%
Unknown or Not Reported	3 1.1%
Height (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	173.24 (8.992)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	80.64 (14.698)
Body Mass Index (BMI) (kg/m²) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m²]	26.76 (3.756)
Body Mass Index (BMI) Group (Count of Participants)
Underweight (<18.5)	1 0.4%
Normal (18.5 to <25)	85 32.1%
Overweight (>=25 to <30)	121 45.7%
Obese (>=30)	58 21.9%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Adverse Events
Description	Overall summary of treatment emergent adverse events during the treatment period
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety population was defined as all subjects who received at least one dose of the study drug

Arm/Group Title	ALKS 3831
Arm/Group Description	All subjects assigned to ALKS 3831 ALKS 3831: Coated bilayer tablet containing 10 mg, 15 mg or 20 mg olanzapine and 10 mg samidorphan Oral tablet, daily dosing
Measure Participants	265
Any Treatment Emergent Adverse Event (TEAE)	161 60.8%
Mild Treatment Emergent Adverse Event (TEAE)	93 35.1%
Moderate Treatment- Emergent Adverse Event (TEAE)	61 23%
Severe Treatment- Emergent Adverse Event (TEAE)	7 2.6%
Treatment- Emergent Adverse Event (TEAE)-Not Related	82 30.9%
Treatment- Emergent Adverse Event (TEAE)-Related	79 29.8%
Adverse Event Leading to Treatment Discontinuation	15 5.7%
Any Serious Adverse Event (SAE)	5 1.9%
Serious Adverse Event (SAE) -Not Related	4 1.5%
Serious Adverse Event (SAE)-Related	1 0.4%
Serious Adverse Event (SAE) leading to Death	0 0%

Adverse Events

Time Frame	52 weeks
Arm/Group Title	ALKS 3831
Arm/Group Description	All subjects assigned to ALKS 3831 in ALKS 3831-A303 and ALKS 3831-A304 ALKS 3831: Coated bilayer tablet containing 10 mg, 15 mg or 20 mg olanzapine and 10 mg samidorphan Oral tablet, daily dosing
All Cause Mortality
	ALKS 3831
	Affected / at Risk (%)	# Events
Total	0/265 (0%)
Serious Adverse Events
	ALKS 3831
	Affected / at Risk (%)	# Events
Total	5/265 (1.9%)
Gastrointestinal disorders
Gastritis alcoholic	1/265 (0.4%)
Psychiatric disorders
Schizophrenia	2/265 (0.8%)
Agitation	1/265 (0.4%)
Psychotic disorder	1/265 (0.4%)
Renal and urinary disorders
Acute kidney injury	1/265 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/265 (0.4%)
Other (Not Including Serious) Adverse Events
	ALKS 3831
	Affected / at Risk (%)	# Events
Total	103/265 (38.9%)
Gastrointestinal disorders
Toothache	7/265 (2.6%)
Nausea	6/265 (2.3%)
Infections and infestations
Upper respiratory tract infection	12/265 (4.5%)
Nasopharyngitis	10/265 (3.8%)
Injury, poisoning and procedural complications
Extra dose administered	21/265 (7.9%)
Investigations
Weight decreased	23/265 (8.7%)
Weight increased	16/265 (6%)
Blood creatine phosphokinase increased	8/265 (3%)
Musculoskeletal and connective tissue disorders
Back pain	9/265 (3.4%)
Nervous system disorders
Headache	18/265 (6.8%)
Vascular disorders
Hypertension	6/265 (2.3%)

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.