A Long-term Safety Study of ALKS 9072 (Also Known as ALKS 9070)

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01626456
• Collaborator: (none)
• Enrollment: 478
• Locations: 82
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the safety and durability of effect of ALKS 9072 (also known as ALKS 9070) during long-term treatment of subjects with stable schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: ALKS 9072, Low; Drug: ALKS 9072, High	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 478 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Extension of Study ALK9072-003 to Assess the Long-term Safety and Durability of Effect of ALKS 9072 in Subjects With Stable Schizophrenia
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALKS 9072, Low	Drug: ALKS 9072, Low; IM injection, given monthly
Experimental: ALKS 9072, High	Drug: ALKS 9072, High; IM injection, given monthly

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Treatment-emergent Adverse Events (TEAEs) [52 weeks]

   This measure includes incidences >5%.

Secondary Outcome Measures

1. Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S) [52 weeks]

   The CGI-S is a 7-point scale that requires the clinician to assess how mentally ill the patient is in a specific point in time. Results indicate participants evaluated at one of the following categories: "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". Results indicate a change in CGI-S score from baseline to Day 365 based on the observed data.

2. Discontinuation From Study Due to Adverse Events (AEs) [52 weeks]

   Number of subjects who discontinued the study due to AE.

3. Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) [52 weeks]

   The C-SSRS is a questionnaire used for suicide assessment. Subjects are asked a series of questions that determine whether or not the patient demonstrates any suicidal ideation or behavior. The C-SSRS was administered to subjects at each study visit.

4. Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests [52 weeks]

   Includes incidence >2% but <5%.

5. Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores [52 weeks]

   This scale consists of symptom constructs (7 positive, 7 negative, 16 general psychopathology), each to be rated on a 7-point Likert-type scale of severity with 1 being absent to 7 being extreme. Minimum scores (best outcome) equals 30 (total scale), 7 (positive/negative subscales), and 16 (general subscale); maximum scores (worst outcome) equals 210 (total scale), 49 (positive/negative subscales), and 112 (general subscale).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

(Subjects who participated in ALK9072-003)

• Completed the ALK9072-003 Day 85 visit

• Continues to require treatment with an antipsychotic medication

(New Subjects)

• On a stable dose of oral antipsychotic medication

• Diagnosis of chronic schizophrenia based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria that is clinically stable

• Has been able to achieve outpatient status for more than 3 months prior to screening

• Body Mass Index (BMI) of 18.5 to 40.0 kg/m2 (inclusive)

• Resides in a stable living situation

Exclusion Criteria:

(Subjects who participated in ALK9072-003)

• Abnormal clinical laboratory, vital sign, or electrocardiogram (ECG) finding during participation in study ALK9072-003 that was clinically relevant and related to study drug

• Missed more than 1 scheduled study visit during participation in study ALK9072-003

• Has a significant or unstable medical condition that would preclude safe completion of the current study

• Subject is pregnant or breastfeeding

• Subject expects to be incarcerated in the next 12 months, or has pending legal action which may impact compliance with study participation or procedures

(New Subjects)

• History of poor or inadequate clinical response to treatment with aripiprazole

• History of treatment resistance

• Diagnosis of current substance dependence (including alcohol)

• Pregnant, lactating, or breastfeeding

• Has received any long-acting intramuscular antipsychotic medication within 60 days prior to screening

• Currently under involuntary hospitalization

• Current or expected incarceration

Additional inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alkermes Investigational Site	Little Rock	Arkansas	United States	72201
2	Alkermes Investigational Site	Little Rock	Arkansas	United States	72211
3	Alkermes Investigational Site	Springdale	Arkansas	United States	72764
4	Alkermes Investigational Site	Garden Grove	California	United States	92845
5	Alkermes Investigational Site	La Habra	California	United States	90631
6	Alkermes Investigational Site	Oakland	California	United States	94612
7	Alkermes Investigational Site	Oceanside	California	United States	92056
8	Alkermes Investigational Site	San Diego	California	United States	92123
9	Alkermes Investigational Site	Washington	District of Columbia	United States	20016
10	Alkermes Investigational Site	Fort Lauderdale	Florida	United States	33308
11	Alkermes Investigational Site	Leesburg	Florida	United States	34748
12	Alkermes Investigational Site	Atlanta	Georgia	United States	30308
13	Alkermes Investigational Site	Chicago	Illinois	United States	60611
14	Alkermes Investigational Site	Chicago	Illinois	United States	60640
15	Alkermes Investigational Site	Hoffman Estates	Illinois	United States	60169
16	Alkermes Investigational Site	Overland Park	Kansas	United States	66212
17	Alkermes Investigational Site	Rockville	Maryland	United States	20850
18	Alkermes Investigational Site	Creve Coeur	Missouri	United States	63141
19	Alkermes Investigational Site	Saint Louis	Missouri	United States	63118
20	Alkermes Investigational Site	Philadelphia	Pennsylvania	United States	19139
21	Alkermes Investigational Site	Charleston	South Carolina	United States	29407
22	Alkermes Investigational Site	Austin	Texas	United States	78731
23	Alkermes Investigational Site	Austin	Texas	United States	78754
24	Alkermes Investigational Site	Dallas	Texas	United States	75231
25	Alkermes Investigational Site	Dallas	Texas	United States	75243
26	Alkermes Investigational Site	Burgas		Bulgaria
27	Alkermes Investigational Site	Kazanlak		Bulgaria
28	Alkermes Investigational Site	Novi Iskar		Bulgaria
29	Alkermes Investigational Site	Pazardzhik		Bulgaria
30	Alkermes Investigational Site	Pleven		Bulgaria
31	Alkermes Investigational Site	Plovdiv		Bulgaria
32	Alkermes Investigational Site	Radnevo		Bulgaria
33	Alkermes Investigational Site	Ruse		Bulgaria
34	Alkermes Investigational Site	Sofia		Bulgaria
35	Alkermes Investigational Site	Stara Zagora		Bulgaria
36	Alkermes Investigational Site	Targovishte		Bulgaria
37	Alkermes Investigational Site	Veliko Tarnovo		Bulgaria
38	Alkermes Investigational Site	Vratsa		Bulgaria
39	Alkermes Investigational Site	Jeju-si		Korea, Republic of
40	Alkermes Investigational Site	Jeollanam-do		Korea, Republic of
41	Alkermes Investigational Site	Seoul		Korea, Republic of
42	Alkermes Investigational Site	Cheras		Malaysia
43	Alkermes Investigational Site	Johor Bahru		Malaysia
44	Alkermes Investigational Site	Kuala Lumpur		Malaysia
45	Alkermes Investigational Site	Kuching		Malaysia
46	Alkermes Investigational Site	Mariveles	Bataan	Philippines
47	Alkermes Investigational Site	Cebu City		Philippines
48	Alkermes Investigational Site	Iloilo City		Philippines
49	Alkermes Investigational Site	Mandaluyong City		Philippines
50	Alkermes Investigational Site	Manila		Philippines
51	Alkermes Investigational Site	Pasig City		Philippines
52	Alkermes Investigational Site	Targu Mures	Mures	Romania
53	Alkermes Investigational Site	Bucharest		Romania
54	Alkermes Investigational Site	Craiova		Romania
55	Alkermes Investigational Site	Iasi		Romania
56	Alkermes Investigational Site	Oradea		Romania
57	Alkermes Investigational Site	Nikol'skoye	Gatchinckiy	Russian Federation
58	Alkermes Investigational Site	Staritsa	Orenburg	Russian Federation
59	Alkermes Investigational Site	Khotkovo		Russian Federation
60	Alkermes Investigational Site	Lipetsk		Russian Federation
61	Alkermes Investigational Site	Moscow		Russian Federation
62	Alkermes Investigational Site	Nizhniy Novgorod		Russian Federation
63	Alkermes Investigational Site	Rostov-on-Don		Russian Federation
64	Alkermes Investigational Site	Samara		Russian Federation
65	Alkermes Investigational Site	Saratov		Russian Federation
66	Alkermes Investigational Site	St. Petersburg		Russian Federation
67	Alkermes Investigational Site	Stavropol		Russian Federation
68	Alkermes Investigational Site	Talagi		Russian Federation
69	Alkermes Investigational Site	Voronezh		Russian Federation
70	Alkermes Investigational Site	Yaroslavl		Russian Federation
71	Alkermes Investigational Site	Stepanovka	Kherson	Ukraine
72	Alkermes Investigational Site	Chernigiv		Ukraine
73	Alkermes Investigational Site	Donetsk		Ukraine
74	Alkermes Investigational Site	Kharkiv		Ukraine
75	Alkermes Investigational Site	Kyiv		Ukraine
76	Alkermes Investigational Site	Lugansk		Ukraine
77	Alkermes Investigational Site	Lviv		Ukraine
78	Alkermes Investigational Site	Poltava		Ukraine
79	Alkermes Investigational Site	Simferopol		Ukraine
80	Alkermes Investigational Site	Ternopil		Ukraine
81	Alkermes Investigational Site	Uzhgorod		Ukraine
82	Alkermes Investigational Site	Vinnytsia		Ukraine

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT01626456
• Other Study ID Numbers: ALK9072-003EXT
• First Posted: Jun 22, 2012
• Last Update Posted: Sep 25, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Schizophrenia

Study Results

Participant Flow

Recruitment Details	Subjects who successfully completed the Day 85 visit in Study ALK9072-003 and continued to meet eligibility criteria were eligible to enroll in this extension study. In addition, adults with chronic stable schizophrenia on a stable oral antipsychotic medication not previously enrolled in Study ALK9072-003 were also eligible to enroll.
Pre-assignment Detail	While there were only 2 treatment groups in this extension study (low dose and high dose), data for several outcome measures is presented by lead-in study groups, and separated into 5 categories: PBO-441 mg, 441-441 mg, PBO-882 mg, 882-882 mg, and de novo.

Arm/Group Title	ALKS 9072, Low	ALKS 9072, High
Arm/Group Description	ALKS 9072, Low: IM injection, given monthly	ALKS 9072, High: IM injection, given monthly
Period Title: Overall Study
STARTED	110	368
COMPLETED	75	251
NOT COMPLETED	35	117

Baseline Characteristics

Arm/Group Title	ALKS 9072, Low	ALKS 9072, High	Total
Arm/Group Description	ALKS 9072, Low: IM injection, given monthly	ALKS 9072, High: IM injection, given monthly	Total of all reporting groups
Overall Participants	110	368	478
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.1 (10.88)	39.8 (11.76)	39.4 (11.57)
Sex: Female, Male (Count of Participants)
Female	45 40.9%	158 42.9%	203 42.5%
Male	65 59.1%	210 57.1%	275 57.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	20 18.2%	59 16%	79 16.5%
Native Hawaiian or Other Pacific Islander	0 0%	2 0.5%	2 0.4%
Black or African American	13 11.8%	79 21.5%	92 19.2%
White	77 70%	228 62%	305 63.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Russian Federation	20 18.2%	60 16.3%	80 16.7%
Romania	3 2.7%	2 0.5%	5 1%
United States	19 17.3%	111 30.2%	130 27.2%
Philippines	17 15.5%	32 8.7%	49 10.3%
Ukraine	29 26.4%	93 25.3%	122 25.5%
Korea, Republic of	0 0%	6 1.6%	6 1.3%
Malaysia	3 2.7%	21 5.7%	24 5%
Bulgaria	19 17.3%	43 11.7%	62 13%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Description	This measure includes incidences >5%.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects who receive at least 1 dose of ALKS 9072 in the current study.

Arm/Group Title	ALKS 9072, Low	ALKS 9072, High
Arm/Group Description	ALKS 9072, Low: IM injection, given monthly	ALKS 9072, High: IM injection, given monthly
Measure Participants	110	368
Number [participants]	51 46.4%	190 51.6%

2. Secondary Outcome

Title	Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S)
Description	The CGI-S is a 7-point scale that requires the clinician to assess how mentally ill the patient is in a specific point in time. Results indicate participants evaluated at one of the following categories: "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". Results indicate a change in CGI-S score from baseline to Day 365 based on the observed data.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set consists of all subjects who received at least 1 dose of ALKS 9072 and had at least 1 postbaseline assessment of PANSS score after administration of ALKS 9072.

Arm/Group Title	PBO-441 mg	441-441 mg	PBO-882 mg	882-882 mg	De Novo
Arm/Group Description	Subjects who received placebo in the base study and low dose in the current study.	Subjects who received low dose in both the base study and the current study.	Subjects who received placebo in the base study and high dose in the current study.	Subjects who received high dose in both the base study and the current study.	Subjects who did not participate in the base study. These subjects received high dose.
Measure Participants	29	80	26	94	233
Mean (Standard Deviation) [units on a scale]	-0.9 (0.68)	-0.5 (0.71)	-0.8 (0.85)	-0.3 (0.61)	-0.2 (0.61)

3. Secondary Outcome

Title	Discontinuation From Study Due to Adverse Events (AEs)
Description	Number of subjects who discontinued the study due to AE.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects who received at least 1 dose of ALKS 9072 in the current study.

Arm/Group Title	ALKS 9072, Low	ALKS 9072, High
Arm/Group Description	ALKS 9072, Low: IM injection, given monthly	ALKS 9072, High: IM injection, given monthly
Measure Participants	110	368
Number [participants]	2 1.8%	27 7.3%

4. Secondary Outcome

Title	Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)
Description	The C-SSRS is a questionnaire used for suicide assessment. Subjects are asked a series of questions that determine whether or not the patient demonstrates any suicidal ideation or behavior. The C-SSRS was administered to subjects at each study visit.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Safety population includes all subjects who received at least 1 dose of ALKS 9072 in the current study.

Arm/Group Title	PBO-440 mg	441-441 mg	PBO-882 mg	882-882 mg	De Novo
Arm/Group Description	Subjects who received placebo in the base study and low dose in the current study	Subjects who received low dose in the base study and in the current study.	Subjects who received placebo in the base study and high dose in the current study.	Subjects who received high dose in the base study and the current study.	Subjects who did not participate in the base study.
Measure Participants	29	81	26	100	242
Any suicidal ideation	0 0%	1 0.3%	1 0.2%	1 NaN	4 NaN
Any suicidal behavior	0 0%	0 0%	0 0%	0 NaN	0 NaN

5. Secondary Outcome

Title	Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests
Description	Includes incidence >2% but <5%.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PBO-441 mg	441-441 mg	PBO-882 mg	882-882 mg	De Novo
Arm/Group Description	Subjects who received placebo in the base study and low dose in the current study.	Subjects who received low dose in both the base study and the current study.	Subjects who received placebo in the base study and high dose in the current study.	Subjects who received high dose in both the base study and the current study.	Subjects who did not participate in the base study. These subjects received high dose.
Measure Participants	29	81	26	100	242
Akathisia	1 0.9%	0 0%	2 0.4%	3 NaN	12 NaN
Tremor	1 0.9%	0 0%	0 0%	4 NaN	7 NaN
Glycosylated haemoglobin increased	0 0%	3 0.8%	0 0%	0 NaN	3 NaN
Hypertension	1 0.9%	0 0%	1 0.2%	3 NaN	4 NaN

6. Secondary Outcome

Title	Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores
Description	This scale consists of symptom constructs (7 positive, 7 negative, 16 general psychopathology), each to be rated on a 7-point Likert-type scale of severity with 1 being absent to 7 being extreme. Minimum scores (best outcome) equals 30 (total scale), 7 (positive/negative subscales), and 16 (general subscale); maximum scores (worst outcome) equals 210 (total scale), 49 (positive/negative subscales), and 112 (general subscale).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set consisted of all subjects who received at least 1 dose of ALKS 9072 and had at least 1 postbaseline assessment of PANSS total score after administration of ALKS 9072.

Arm/Group Title	PBO-441 mg	441-441 mg	PBO-882 mg	882-882 mg	De Novo
Arm/Group Description	Subjects who received placebo in the base study and low dose in the current study.	Subjects who received low dose in both the base study and the current study.	Subjects who received placebo in the base study and high dose in the current study.	Subjects who received high dose in both the base study and the current study.	Subjects who did not participate in the base study. These subjects received high dose.
Measure Participants	29	80	26	94	233
Total Score	-19.1 (15.5)	-10.0 (10.2)	-11.6 (11.7)	-8.3 (8.2)	-5.9 (8.3)
Positive Subscale Score	-5.8 (6.0)	-3.4 (3.4)	-4.1 (4.1)	-2.3 (3.1)	-1.8 (2.8)
Negative Subscale Score	-4.1 (4.2)	-1.5 (3.5)	-1.6 (3.8)	-2.1 (3.0)	-1.2 (3.3)
General Psychopathology Subscale Score	-9.2 (7.6)	-5.1 (5.6)	-5.9 (6.1)	-4.0 (4.7)	-2.9 (4.7)

Adverse Events

Time Frame	Adverse events were collected at every study visit for 1 year (365 days).
Arm/Group Title	ALKS 9072, Low		ALKS 9072, High
Arm/Group Description	ALKS 9072, Low: IM injection, given monthly		ALKS 9072, High: IM injection, given monthly
All Cause Mortality
	ALKS 9072, Low		ALKS 9072, High
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ALKS 9072, Low		ALKS 9072, High
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/110 (0%)		15/368 (4.1%)
Cardiac disorders
Acute myocardial infarction	0/110 (0%)	0	1/368 (0.3%)	1
Cardiac failure congestive	0/110 (0%)	0	1/368 (0.3%)	1
Cardio-respiratory arrest	0/110 (0%)	0	1/368 (0.3%)	1
Metabolism and nutrition disorders
Hyperglycaemia	0/110 (0%)	0	1/368 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/110 (0%)	0	1/368 (0.3%)	1
Nervous system disorders
Cerebrovascular accident	0/110 (0%)	0	1/368 (0.3%)	1
Convulsion	0/110 (0%)	0	1/368 (0.3%)	1
Psychiatric disorders
Schizophrenia	0/110 (0%)	0	2/368 (0.5%)	2
Aggression	0/110 (0%)	0	1/368 (0.3%)	1
Completed suicide	0/110 (0%)	0	1/368 (0.3%)	1
Depressed mood	0/110 (0%)	0	1/368 (0.3%)	1
Drug abuse	0/110 (0%)	0	1/368 (0.3%)	1
Somatoform disorder cardiovascular	0/110 (0%)	0	1/368 (0.3%)	1
Reproductive system and breast disorders
Adenomyosis	0/110 (0%)	0	1/368 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/110 (0%)	0	2/368 (0.5%)	2
Asthma	0/110 (0%)	0	1/368 (0.3%)	1
Pulmonary mass	0/110 (0%)	0	1/368 (0.3%)	1
Other (Not Including Serious) Adverse Events
	ALKS 9072, Low		ALKS 9072, High
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/110 (14.5%)		59/368 (16%)
Investigations
Weight increased	7/110 (6.4%)	8	17/368 (4.6%)	17
Nervous system disorders
Headache	7/110 (6.4%)	10	11/368 (3%)	15
Psychiatric disorders
Insomnia	3/110 (2.7%)	4	37/368 (10.1%)	45

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.