A Study to Evaluate the Efficacy and Safety of ALKS 9072 (Also Known as Aripiprazole Lauroxil, ALKS 9070, or ARISTADA) in Subjects With Schizophrenia

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01469039
• Collaborator: (none)
• Enrollment: 623
• Locations: 84
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The study will determine the efficacy of ALKS 9072 (also known as aripiprazole lauroxil or ALKS 9070) for the treatment of schizophrenia in subjects experiencing an acute exacerbation.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: ALKS 9072; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 623 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of ALKS 9072 in Subjects With Acute Exacerbation of Schizophrenia
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALKS 9072	Drug: ALKS 9072; Intramuscular (IM) injection, 441 mg or 882 mg given monthly
Placebo Comparator: Placebo	Drug: Placebo; Placebo for IM injection, given monthly

Outcome Measures

Primary Outcome Measures

1. The Change From Baseline at Day 85 in Positive and Negative Syndrome Scale (PANSS) Total Score [Data collected from baseline to day 85]

   The PANSS scale contains 30 questions, each containing an answer range of 1-7. A total PANSS score can range from between 30 to 210; a higher score indicates a worse disease condition.

Secondary Outcome Measures

1. Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 [85 Days]

   The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the study. Results indicate participants evaluated at one of the following categories: "1: very much improved"; "2: much improved"; "3: minimally improved"; "4: no change"; "5: minimally worse"; "6: much worse"; or "7: very much worse".

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of schizophrenia according to DSM-IV-TR criteria

• Has been able to achieve outpatient status for more than 3 months in the past year

• Body mass index (BMI) of 18.5 to 40.0 kg/m2 (inclusive)

• Resides in a stable living situation

• Willing and able to be confined to an inpatient study unit for 2 weeks or longer

Exclusion Criteria:

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

• History of treatment resistance

• Known or suspected intolerance of, allergy, or hypersensitivity to aripiprazole, its ingredients, other antipsychotic agent, or INTRALIPID (including peanuts, soy, egg, or glycerol)

• Diagnosis of current substance dependence (including alcohol)

• Pregnant, lactating, or breastfeeding

• Receipt of any antipsychotic medication by IM injection within 60 days before Screening

• Current involuntary hospitalization or incarceration

• Hospitalized for more than 30 days during the 90 days before Screening

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	Cerritos	California	United States	90703
5	Alkermes Investigational Site	Garden Grove	California	United States	92845
6	Alkermes Investigational Site	La Habra	California	United States	90631
7	Alkermes Investigational Site	Oakland	California	United States	94612
8	Alkermes Investigational Site	Oceanside	California	United States	92056
9	Alkermes Investigational Site	Orange	California	United States	92868
10	Alkermes Investigational Site	San Diego	California	United States	92123
11	Alkermes Investigational Site	Washington	District of Columbia	United States	20016
12	Alkermes Investigational Site	Fort Lauderdale	Florida	United States	33308
13	Alkermes Investigational site	Leesburg	Florida	United States	34748
14	Alkermes Investigational Site	Atlanta	Georgia	United States	30308
15	Alkermes Investigational Site	Chicago	Illinois	United States	60640
16	Alkermes Investigational Site	Hoffman Estates	Illinois	United States	60169
17	Alkermes Investigational Site	Overland Park	Kansas	United States	66212
18	Alkermes Investigational Site	Rockville	Maryland	United States	20850
19	Alkermes Investigational Site	Creve Coeur	Missouri	United States	63141
20	Alkermes Investigational Site	Saint Louis	Missouri	United States	63118
21	Alkermes Investigational Site	Philadelphia	Pennsylvania	United States	19139
22	Alkermes Investigational Site	Charleston	South Carolina	United States	29407
23	Alkermes Investigational Site	Austin	Texas	United States	78731
24	Alkermes Investigational Site	Austin	Texas	United States	78754
25	Alkermes Investigational Site	Dallas	Texas	United States	75231
26	Alkermes Investigational Site	Dallas	Texas	United States	75243
27	Alkermes Investigational Site	Burgas		Bulgaria
28	Alkermes Investigational Site	Kazanlak		Bulgaria
29	Alkermes Investigational Site	Novi Iskar		Bulgaria
30	Alkermes Investigational Site	Pazardzhik		Bulgaria
31	Alkermes Investigational Site	Pleven		Bulgaria
32	Alkermes Investigational Site	Plovdiv		Bulgaria
33	Alkermes Investigational Site	Radnevo		Bulgaria
34	Alkermes Investigational Site	Ruse		Bulgaria
35	Alkermes Investigational Site	Sofia		Bulgaria
36	Alkermes Investigational Site	Stara Zagora		Bulgaria
37	Alkermes Investigational Site	Targovishte		Bulgaria
38	Alkermes Investigational Site	Veliko Tarnovo		Bulgaria
39	Alkermes Investigational Site	Vratsa		Bulgaria
40	Alkermes Investigational Site	Jeju-si		Korea, Republic of
41	Alkermes Investigational Site	Jeollanam-do		Korea, Republic of
42	Alkermes Investigational Site	Seoul		Korea, Republic of
43	Alkermes Investigational Site	Cheras		Malaysia
44	Alkermes Investigational Site	Johor Bahru		Malaysia
45	Alkermes Investigational Site	Kuala Lumpur		Malaysia
46	Alkermes Investigational Site	Kuching		Malaysia
47	Alkermes Investigational Site	Mariveles	Bataan	Philippines
48	Alkermes Investigational Site	Cebu City		Philippines
49	Alkermes Investigational Site	Iloilo City		Philippines
50	Alkermes Investigational Site	Mandaluyong City		Philippines
51	Alkermes Investigational Site	Manila		Philippines
52	Alkermes Investigational Site	Pasig City		Philippines
53	Alkermes Investigational Site	Oradea	Bihor	Romania
54	Alkermes Investigational Site	Bucharest		Romania	030455
55	Alkermes Investigational Site	Bucharest		Romania
56	Alkermes Investigational Site	Craiova		Romania
57	Alkermes Investigational Site	Iasi		Romania
58	Alkermes Investigational Site	Targu Mures		Romania
59	Alkermes Investigational Site	Nikol'skoye	Gatchinckiy	Russian Federation
60	Alkermes Investigational Site	Staritsa	Orenburg	Russian Federation
61	Alkermes Investigational Site	Talagi	Primorsky	Russian Federation
62	Alkermes Investigational Site	Khotkovo	Sergievo-Posadskiy	Russian Federation
63	Alkermes Investigational Site	Lipetsk		Russian Federation
64	Alkermes Investigational Site	Moscow		Russian Federation
65	Alkermes Investigational Site	Nizhniy Novgorod		Russian Federation
66	Alkermes Investigational Site	Rostov-on-Don		Russian Federation
67	Alkermes Investigational Site	Samara		Russian Federation
68	Alkermes Investigational Site	Saratov		Russian Federation
69	Alkermes Investigational Site	St. Petersburg		Russian Federation
70	Alkermes Investigational Site	Stavropol		Russian Federation
71	Alkermes Investigational Site	Voronezh		Russian Federation
72	Alkermes Investigational Site	Yaroslavl		Russian Federation
73	Alkermes Investigational Site	Stepanovka	Kherson	Ukraine
74	Alkermes Investigational Site	Chernigiv		Ukraine
75	Alkermes Investigational Site	Donetsk		Ukraine
76	Alkermes Investigational Site	Kharkiv		Ukraine
77	Alkermes Investigational Site	Kyiv		Ukraine
78	Alkermes Investigational Site	Lugansk		Ukraine
79	Alkermes Investigational Site	Lviv		Ukraine
80	Alkermes Investigational Site	Poltava		Ukraine
81	Alkermes Investigational Site	Simferopol		Ukraine
82	Alkermes Investigational Site	Ternopil		Ukraine
83	Alkermes Investigational Site	Uzhgorod		Ukraine
84	Alkermes Investigational Site	Vinnytsya		Ukraine

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Russian clinical trials website
• EU Clinical Trials Register; EudraCT number 2012-003445-15

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT01469039
• Other Study ID Numbers: ALK9072-003
• First Posted: Nov 10, 2011
• Last Update Posted: Jan 30, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Alkermes, Inc.: Alkermes; schizophrenia; ALKS 9072; ALKS 9070; aripiprazole lauroxil
• Additional relevant MeSH terms: Schizophrenia

Study Results

Participant Flow

Recruitment Details	Included subjects with schizophrenia experiencing an acute exacerbation episode.
Pre-assignment Detail	Subjects were admitted to an inpatient study unit. Currently prescribed antipsychotics were discontinued prior to administration of study drug. One randomized subject was discontinued for a protocol violation prior to receiving investigational treatment.

Arm/Group Title	Aripiprazole Lauroxil 441 mg	Aripiprazole Lauroxil 882 mg	Placebo
Arm/Group Description	Intramuscular injection, given monthly	Intramuscular injection, given monthly	Intramuscular injection, given monthly
Period Title: Overall Study
STARTED	207	208	208
COMPLETED	130	135	95
NOT COMPLETED	77	73	113

Baseline Characteristics

Arm/Group Title	Aripiprazole Lauroxil 441 mg	Aripiprazole Lauroxil 882 mg	Placebo	Total
Arm/Group Description	Intramuscular injection, given monthly	Intramuscular injection, given monthly	Intramuscular injection, given monthly	Total of all reporting groups
Overall Participants	207	208	208	623
Age (Count of Participants)
<=18 years	2 1%	0 0%	1 0.5%	3 0.5%
Between 18 and 65 years	205 99%	207 99.5%	206 99%	618 99.2%
>=65 years	0 0%	1 0.5%	1 0.5%	2 0.3%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.9 (10.13)	39.7 (11.06)	39.5 (11.85)	39.7 (11.02)
Sex: Female, Male (Count of Participants)
Female	66 31.9%	65 31.3%	69 33.2%	200 32.1%
Male	141 68.1%	143 68.8%	139 66.8%	423 67.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.5%	1 0.5%	2 0.3%
Asian	24 11.6%	28 13.5%	29 13.9%	81 13%
Native Hawaiian or Other Pacific Islander	1 0.5%	0 0%	0 0%	1 0.2%
Black or African American	83 40.1%	81 38.9%	84 40.4%	248 39.8%
White	99 47.8%	98 47.1%	94 45.2%	291 46.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	103 49.8%	102 49%	102 49%	307 49.3%
Philippines	16 7.7%	21 10.1%	16 7.7%	53 8.5%
Malaysia	7 3.4%	7 3.4%	10 4.8%	24 3.9%
Ukraine	29 14%	29 13.9%	32 15.4%	90 14.4%
Romania	5 2.4%	6 2.9%	6 2.9%	17 2.7%
Bulgaria	23 11.1%	19 9.1%	17 8.2%	59 9.5%
Russian Federation	24 11.6%	24 11.5%	25 12%	73 11.7%

Outcome Measures

1. Primary Outcome

Title	The Change From Baseline at Day 85 in Positive and Negative Syndrome Scale (PANSS) Total Score
Description	The PANSS scale contains 30 questions, each containing an answer range of 1-7. A total PANSS score can range from between 30 to 210; a higher score indicates a worse disease condition.
Time Frame	Data collected from baseline to day 85

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) defined as all randomized subjects who received at least 1 dose of IM study drug and had at least 1 primary efficacy assessment after administration of IM study drug.

Arm/Group Title	Aripiprazole Lauroxil 441 mg	Aripiprazole Lauroxil 882 mg	Placebo
Arm/Group Description	Intramuscular injection, given monthly	Intramuscular injection, given monthly	Intramuscular injection, given monthly
Measure Participants	196	204	196
Least Squares Mean (Standard Error) [units on a scale]	-20.9 (1.39)	-21.8 (1.35)	-9.8 (1.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Lauroxil 441 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Lauroxil 882 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Clinical Global Impression - Improvement (CGI-I) Scores at Day 85
Description	The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the study. Results indicate participants evaluated at one of the following categories: "1: very much improved"; "2: much improved"; "3: minimally improved"; "4: no change"; "5: minimally worse"; "6: much worse"; or "7: very much worse".
Time Frame	85 Days

Outcome Measure Data

Analysis Population Description

FAS, defined as all randomized subjects who received at least 1 IM dose of study drug and had at least 1 primary efficacy assessment after administration of IM study drug.

Arm/Group Title	Aripiprazole Lauroxil 441 mg	Aripiprazole Lauroxil 882 mg	Placebo
Arm/Group Description	Intramuscular injection, given monthly	Intramuscular injection, given monthly	Intramuscular injection, given monthly
Measure Participants	196	204	196
CGI Score: Very much improved	27 13%	25 12%	15 7.2%
CGI Score: Much improved	68 32.9%	81 38.9%	33 15.9%
GCI Score: Minimally improved	45 21.7%	52 25%	43 20.7%
CGI Score: No change	32 15.5%	24 11.5%	42 20.2%
CGI Score: Minimally worse	11 5.3%	16 7.7%	37 17.8%
CGI Score: Much worse	12 5.8%	5 2.4%	23 11.1%
CGI Score: Very much worse	1 0.5%	1 0.5%	3 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Lauroxil 441 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	significant p-value, active vs placebo
	Method	Wilcoxon rank sum test based on LOCF
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Lauroxil 882 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	significant p-value, active vs placebo
	Method	Wilcoxon rank sum test based on LOCF
	Comments

Adverse Events

Time Frame	Adverse events were collected during the 85-day treatment period.
Adverse Event Reporting Description	One randomized subject was discontinued for a protocol violation prior to receiving IM study drug (placebo), and this subject was not included in the safety population. This changes the overall number of subjects in the placebo group to include 207.
Arm/Group Title	Aripiprazole Lauroxil 441 mg		Aripiprazole Lauroxil 882 mg		Placebo
Arm/Group Description	Intramuscular injection, given monthly		Intramuscular injection, given monthly		Intramuscular injection, given monthly
All Cause Mortality
	Aripiprazole Lauroxil 441 mg		Aripiprazole Lauroxil 882 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Aripiprazole Lauroxil 441 mg		Aripiprazole Lauroxil 882 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/207 (1.4%)		4/208 (1.9%)		4/207 (1.9%)
Cardiac disorders
Angina unstable	1/207 (0.5%)	1	0/208 (0%)	0	0/207 (0%)	0
Gastrointestinal disorders
Peritoneal adhesions	1/207 (0.5%)	1	0/208 (0%)	0	0/207 (0%)	0
Infections and infestations
Appendicitis	1/207 (0.5%)	1	0/208 (0%)	0	0/207 (0%)	0
Pneumonia	0/207 (0%)	0	0/208 (0%)	0	1/207 (0.5%)	1
Metabolism and nutrition disorders
Hypoglycaemia	0/207 (0%)	0	1/208 (0.5%)	1	0/207 (0%)	0
Nervous system disorders
Akathisia	0/207 (0%)	0	1/208 (0.5%)	1	0/207 (0%)	0
Psychiatric disorders
Drug Abuse	0/207 (0%)	0	1/208 (0.5%)	1	0/207 (0%)	0
Psychotic disorder	0/207 (0%)	0	0/208 (0%)	0	1/207 (0.5%)	1
Suicide attempt	0/207 (0%)	0	0/208 (0%)	0	1/207 (0.5%)	1
Reproductive system and breast disorders
Cervical dysplasia	0/207 (0%)	0	1/208 (0.5%)	1	0/207 (0%)	0
Social circumstances
Victim of homicide	0/207 (0%)	0	0/208 (0%)	0	1/207 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Aripiprazole Lauroxil 441 mg		Aripiprazole Lauroxil 882 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/207 (31.9%)		68/208 (32.7%)		76/207 (36.7%)
Nervous system disorders
Akathisia	24/207 (11.6%)	26	23/208 (11.1%)	30	9/207 (4.3%)	9
Headache	17/207 (8.2%)	20	18/208 (8.7%)	22	17/207 (8.2%)	20
Psychiatric disorders
Agitation	3/207 (1.4%)	4	3/208 (1.4%)	3	11/207 (5.3%)	11
Anxiety	6/207 (2.9%)	11	11/208 (5.3%)	14	14/207 (6.8%)	16
Insomnia	20/207 (9.7%)	26	25/208 (12%)	27	24/207 (11.6%)	29
Schizophrenia	12/207 (5.8%)	13	5/208 (2.4%)	5	22/207 (10.6%)	22

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.