ASPIRE: Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00731549
• Collaborator: Covance (Industry)
• Enrollment: 1,081
• Locations: 214
• Arm: 1
• Duration (Months): 59
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the overall effectiveness of aripiprazole intramuscular (IM) depot as maintenance treatment in patients with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Aripiprazole IM Depot	Phase 3

Detailed Description

This will be an open-label, uncontrolled study which will enroll subjects from Phase 4 of Study 31-07-246 and Phase 3 of Study 31- 07-247 and new subjects not participating in Studies 246/247. The treatment history of subjects prior to enrollment in the open-label study will vary according to the design of the pivotal double-blind study (i.e., 31-07-246 or 31-07-247).

This open-label study will be comprised of phases similar to the pivotal double-blind studies (i.e., Studies 246/247): a screening phase (if applicable), a conversion phase (Phase 1, if applicable), an oral stabilization phase (Phase 2), and an IM depot open-label maintenance phase (Phase 3). Phase 3 will be a 52-week treatment period with a 26-week follow-up period.

During Phase 3 (the open-label maintenance phase) oral aripiprazole rescue medication will be allowed for subjects who do not meet stability criteria or meet the criteria for impending relapse/exacerbation of psychotic symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1081 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52-week, Multicenter, Open-label Study to Evaluate the Effectiveness of Aripiprazole Intramuscular Depot as Maintenance Treatment in Patients With Schizophrenia
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Active Treatment of aripiprazole IM depot (300mg or 400mg)	Drug: Aripiprazole IM Depot; 300mg or 400mg; Other Names: Oral Aripiprazole

Outcome Measures

Primary Outcome Measures

1. Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit). [Baseline to Week 52/Last visit]

   "Stable" was defined as meeting all of the following criteria: Outpatient status; Positive and negative syndrome scale (PANSS) total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at endpoint (last visit) is described here.

Secondary Outcome Measures

1. Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. [Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48,52, and Last visit (upto 4 weeks ± 3 days after completion or withdrawal)]

   "Impending relapse criteria" was defined as meeting all the following criteria: 1) Clinical Global Impression of Improvement (CGI-I) ≥ 5 (minimally worse), AND an increase to score of >4 and absolute increase of ≥ 2 on the individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content); or an increase to score >4 and absolute increase of ≥ 4 on the combined 4 PANSS items on any of these PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) OR 2) Hospitalization due to worsening of psychotic symptoms, but excluding hospitalization for psychosocial reasons, OR 3) CGI-SS score of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2, OR 4) Violent behavior resulting in clinically relevant self-injury, injury to another person, or property damage.

2. Percentage of Participants Achieving Remission. [Overall remission from Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48 and 52]

   Remission is defined as a score of ≤ 3 on each of the following specific PANSS items, maintained for a period of six months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, social withdrawal, and lack of spontaneity.

3. Percentage of Participants Stable at Baseline and Remaining Stable at Week 28. [Baseline to Week 28]

   "Stable" was defined as meeting all of the following criteria: Outpatient status; PANSS total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at Week 28 is described here.

4. Percentage of Participants With Time to First Exacerbation of Psychotic Symptoms/Impending Relapse. [Baseline to Week 52]

   Participants who first time meet relapse criteria were considered as having an event at date of exacerbation of psychotic symptoms/impending relapse. Time to first event was calculated as the earliest date of meeting one of relapse criteria. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.

5. Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score. [Baseline, Weeks 12, 24, 52 and last visit]

   PANSS total score (range 30-210) is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS scale. PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.

6. Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score. [Baseline, Weeks 12, 24, 52 and last visit]

   To assess CGI-S, the rater or physician will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices include: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

7. Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales. [Baseline, Weeks 12, 24, 52 and last visit]

   PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. Positive subscale consists of 7 positive symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. Negative subscale consists of 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive pathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking). The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.

8. Mean Clinical Global Impression of Improvement (CGI-I) Score. [Weeks 2, 4, 12, 24, 52 and last visit]

   To assess CGI-I the rater or physician will rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses will be compared to the participants condition at baseline. Response choices include: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

9. Percentage of Participants Who Discontinued Due to All Causes. [Baseline to Week 52]

   Participants who discontinued due to any cause were noted. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as require by IRB/IEC), prior to the initiation of any protocol-required procedures.

• Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.

• Subjects who complete Studies 246/247 or who withdrew from the double-blind maintenance phase of either study (Phase 4 of Study 246 or Phase 3 of Study 247), or new subjects not participating in Studies 246/247.

• Subjects who, in the investigator's judgment, require chronic treatment with an

antipsychotic medication.

• Subjects able to understand the nature of the study and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, IM depot injection, discontinuation of prohibited concomitant medications, who can read and understand the written word in order to complete patient-reported outcomes measures, and who can be reliably rated on assessment scales.

Exclusion Criteria:

• Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder.

• Subjects with schizophrenia that are considered resistant/refractory to antipsychotic treatment by history or response only to clozapine.

• Subjects with a significant risk of violent behavior or a significant risk of committing suicide based on history or investigator's judgment.

• Subjects who currently meet DSM-IV-TR criteria for substance dependence; including alcohol and benzodiazepines, but excluding caffeine and nicotine, or two positive drug screens for cocaine.

• Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.

• Subjects with a history of hypersensitivity to antipsychotic agents.

• Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Chandler	Arizona	United States	85226
2		Anaheim	California	United States	92804
3		Cerritos	California	United States	90703
4		Chino	California	United States	91710
5		Escondido	California	United States	92025
6		Garden Grove	California	United States	92845
7		Glendale	California	United States	91204
8		Glendale	California	United States	91206
9		Imperial	California	United States	92251
10		La Habra	California	United States	90631
11		Los Angeles	California	United States	90024
12		National City	California	United States	91950
13		Oceanside	California	United States	92056
14		Orange	California	United States	92868
15		Pasadena	California	United States	91106
16		Pico Rivera	California	United States	90660
17		San Bernardino	California	United States	92408
18		San Diego	California	United States	92102
19		San Diego	California	United States	92103
20	Study Site	San Diego	California	United States	92123
21		San Diego	California	United States	92123
22		Sherman Oaks	California	United States	91403
23		Torrance	California	United States	90502
24		Highlands Ranch	Colorado	United States	80130
25		Norwalk	Connecticut	United States	06851
26		Washington	District of Columbia	United States	20016
27		Bradenton	Florida	United States	34208
28		Coral Springs	Florida	United States	33065
29		Doral	Florida	United States	33166
30		Gainesville	Florida	United States	32606
31		Hollywood	Florida	United States	33021
32		Kissimmee	Florida	United States	34741
33		Maitland	Florida	United States	32751
34		Miami	Florida	United States	33135
35		Orange City	Florida	United States	32763
36		Orlando	Florida	United States	32839
37		Plantation	Florida	United States	33317
38		Tampa	Florida	United States	33613
39		Atlanta	Georgia	United States	30328
40		Chicago	Illinois	United States	60612
41		Chicago	Illinois	United States	60640
42		Hoffman Estates	Illinois	United States	60169
43		Oak Brook	Illinois	United States	60523
44		Indianapolis	Indiana	United States	46222
45		Baton Rouge	Louisiana	United States	70808
46		Baton Rouge	Louisiana	United States	70809
47		Lake Charles	Louisiana	United States	70629
48		New Orleans	Louisiana	United States	70115
49		Shreveport	Louisiana	United States	71101
50		Columbia	Maryland	United States	21045
51		Flowood	Mississippi	United States	39232
52		Kansas City	Missouri	United States	64108
53		St. Louis	Missouri	United States	63109
54		St. Louis	Missouri	United States	63118
55		North Platte	Nebraska	United States	69101
56		Albuquerque	New Mexico	United States	87131
57		Buffalo	New York	United States	14213
58		Buffalo	New York	United States	14215
59		Cedarhurst	New York	United States	11516
60		Holliswood	New York	United States	11423
61		Jamaica	New York	United States	11418
62		New York	New York	United States	10003
63		New York	New York	United States	10027
64		Rochester	New York	United States	14615
65		Hickory	North Carolina	United States	28601
66		Winston-Salem	North Carolina	United States	27104
67		Canton	Ohio	United States	44718
68		Cincinnati	Ohio	United States	45219
69		Cleveland	Ohio	United States	44109
70		Garfield Heights	Ohio	United States	44125
71		Middleburg Heights	Ohio	United States	44130
72		Toledo	Ohio	United States	43609
73		Oklahoma City	Oklahoma	United States	73103
74		Oklahoma City	Oklahoma	United States	73112
75		Oklahoma City	Oklahoma	United States	73139
76		Allentown	Pennsylvania	United States	18104
77		Jenkintown	Pennsylvania	United States	19046
78		Media	Pennsylvania	United States	19063
79		Philadelphia	Pennsylvania	United States	19131
80		Philadelphia	Pennsylvania	United States	19139
81		Pittsburgh	Pennsylvania	United States	15213
82		Sellersville	Pennsylvania	United States	18960
83		Charleston	South Carolina	United States	29401
84		Charleston	South Carolina	United States	29407
85		Charleston	South Carolina	United States	29425
86		Johnson City	Tennessee	United States	37614-1707
87		Memphis	Tennessee	United States	38119
88		Nashville	Tennessee	United States	37212
89		Austin	Texas	United States	78731
90		Austin	Texas	United States	78754
91		DeSoto	Texas	United States	75115
92		Richmond	Virginia	United States	23230
93		Bellevue	Washington	United States	98007
94		Bothell	Washington	United States	98011
95		Spokane	Washington	United States	99204
96		Milwaukee	Wisconsin	United States	53226
97		Buenos Aires		Argentina	C1058AAJ
98		Buenos Aires		Argentina	C1405BOA
99		Buenos Aires		Argentina	C1425AHQ
100		Cordoba, Cordoba		Argentina	X5009BIN
101		La Plata, Buenos Aires		Argentina
102		Mendoza		Argentina	5500HYF
103		Dandenong	Victoria	Australia	3175
104		Epping	Victoria	Australia	3076
105		Frankston	Victoria	Australia	3199
106		Fremantle	Western Australia	Australia	6959
107		Glenside, SA		Australia	5063
108		Melbourne		Australia	VIC 3004
109		Innsbruck		Austria	A-6020
110		Brugge		Belgium	8200
111		Bourgas		Bulgaria	8000
112		Lovech		Bulgaria	5500
113		Pazardjik		Bulgaria	4400
114		Pleven		Bulgaria	5800
115		Plovdiv		Bulgaria	4002
116		Radnevo		Bulgaria	6260
117		Rousse		Bulgaria	7003
118		Sofia		Bulgaria	1113
119		Sofia		Bulgaria	1431
120		Sofia		Bulgaria	1632
121		Varna		Bulgaria	9001
122		Veliko Tarnovo		Bulgaria	5007
123		San Bernardo, Santiago		Chile	8780000
124		Santiago		Chile	7500710
125		Santiago		Chile	7510186
126		Santiago		Chile	7580307
127		Santiago		Chile	8330838
128		Santiago		Chile	8900085
129		Santiago		Chile
130		Zagreb		Croatia	10 090
131		Zagreb		Croatia	10000
132		Jamejala		Estonia	71024
133		Tallinn		Estonia	10614
134		Tallinn		Estonia	10617
135		Tartu		Estonia	50406
136		Helsinki		Finland	00250
137		Elancourt		France	78990
138		Rennes		France	35703
139		St. Nazaire		France	44606
140		Baja		Hungary	6500
141		Balassagyarmat		Hungary	2660
142		Cegléd		Hungary	2700
143		Gyor		Hungary	9023
144		Ahmedabad	Gujarat	India	380006
145		Bangalore	Karnataka	India	560010
146		Chennai	Tamil Nadu	India	600003
147		Kanpur		India	208005
148		Mangalore		India	575018
149		Pune		India	411004
150		Tirupati		India	517507
151		Busan		Korea, Republic of	614-735
152		Deajeon		Korea, Republic of	301-721
153		Gwangju		Korea, Republic of	501-757
154		Joong-gu, Incheon		Korea, Republic of	400-700
155		Seoul		Korea, Republic of	110-744
156		Seoul		Korea, Republic of	137-701
157		Seoul		Korea, Republic of	150-950
158		Tanjong Rambutan	Perak	Malaysia	31250
159		Kuala Lumpur	Wilayah Persekutuan	Malaysia	50603
160		Kuala Lumpur	Wilayah Persekutuan	Malaysia	56000
161		Selangor		Malaysia	43000
162		Mexico	DF	Mexico	6700
163		Guadalajara	Jalisco	Mexico	44280
164		Monterrey	Nuevo León	Mexico	64040
165		Culiacan	Sinaloa	Mexico	80020
166		San Luis Potosí		Mexico	78218
167		Aalesund		Norway	6018
168		Klepp stasjon		Norway	4353
169		Bataan	Central Luzon	Philippines	2105
170		Mandaluyong	NCR	Philippines	1553
171		Quezon City	NCR	Philippines	1104
172		Iloilo	Western Visayas	Philippines	5000
173		Belchatow		Poland	97-400
174		Bialystok		Poland	15-879
175		Bydgoszcz		Poland	85096
176		Choroszcz		Poland	16-070
177		Kraków		Poland	31-501
178		Leszno		Poland	64-100
179		Pruszkow		Poland	05-802
180		Sosnowiec		Poland	41-200
181		Wroclaw		Poland	50-227
182		San Juan		Puerto Rico	00918
183		Arad		Romania	310022
184		Bucuresti		Romania	041914
185		Cluj-Napoca		Romania	400012
186		Craiova		Romania	200620
187		Oradea		Romania	410154
188		Pitesti		Romania	110069
189		Lipetsk		Russian Federation	398007
190		Moscow		Russian Federation	115522
191		Moscow		Russian Federation	127083
192		Nizhny Novgorod		Russian Federation	603152
193		Nizhny Novgorod		Russian Federation	603155
194		Smolensk		Russian Federation	214019
195		St. Petersburg		Russian Federation	188357
196		St. Petersburg		Russian Federation	190121
197		St. Petersburg		Russian Federation	192019
198		Belgrade		Serbia	11000
199		Kragujevac		Serbia	34000
200		Kosice		Slovakia	041 90
201		Liptovsky Mikulas		Slovakia	3101
202		Presov		Slovakia	8001
203		Rimavska Sobota		Slovakia	97901
204		Svidnik		Slovakia	089 01
205		Pretoria	Gauteng	South Africa	0001
206		Cape Town	Western Province	South Africa	7530
207		Barcelona		Spain	08036
208		Barcelona		Spain	08907
209		Barcelona		Spain	8005
210		Tainan		Taiwan	704
211		Taipei		Taiwan	11086
212		Muang	Chiangmai	Thailand	50100
213		Muang	Chiangmai	Thailand	50200
214		Bangkok		Thailand	10330

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.
• Covance

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT00731549
• Other Study ID Numbers: 31-08-248
• First Posted: Aug 11, 2008
• Last Update Posted: Nov 26, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Aripiprazole; IM Depot; Schizophrenia; Intramuscular
• Additional relevant MeSH terms: Schizophrenia; Aripiprazole

Study Results

Participant Flow

Recruitment Details	This open label Phase 3 study enrolled participants from the maintenance phase of study NCT00705783 (31-07-246) and study NCT00706654 (31-07-247) and new participants. Participants received aripiprazole intramuscular (IM) depot as maintenance treatment.
Pre-assignment Detail	Study comprised of screening phase (applicable if enrolled late/new participants/received antipsychotic treatment other than aripiprazole), conversion phase (Phase 1, to convert from other antipsychotics to aripiprazole), oral stabilization phase (Phase 2-aripiprazole 10-30 mg), and open-label IM phase (Phase 3-aripiprazole 400 mg IM depot).

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Period Title: Overall Study
STARTED	1081
COMPLETED	858
NOT COMPLETED	223

Baseline Characteristics

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Overall Participants	1081
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.2 (10.6)
Sex: Female, Male (Count of Participants)
Female	439 40.6%
Male	642 59.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Stable Participants at Baseline Who Remained Stable at Endpoint (Last Visit).
Description	"Stable" was defined as meeting all of the following criteria: Outpatient status; Positive and negative syndrome scale (PANSS) total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at endpoint (last visit) is described here.
Time Frame	Baseline to Week 52/Last visit

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of stable participants at baseline who were evaluated at the specified trial week.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Baseline (N=1075)	100 9.3%
Week 2 (N=1023)	99.02 9.2%
Week 4 (N=1045)	99.14 9.2%
Week 8 (N=1009)	98.51 9.1%
Week 12 (N=988)	97.47 9%
Week 16 (N=951)	98.42 9.1%
Week 20 (N=919)	98.15 9.1%
Week 24 (N=880)	99.20 9.2%
Week 28 (N=854)	98.95 9.2%
Week 32 (N=838)	99.16 9.2%
Week 36 (N=814)	99.26 9.2%
Week 40 (N=807)	99.50 9.2%
Week 44 (N=784)	99.11 9.2%
Week 48 (N=751)	99.20 9.2%
Week 52 (N=671)	98.96 9.2%
Last visit (N=1072)	94.96 8.8%

2. Secondary Outcome

Title	Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria.
Description	"Impending relapse criteria" was defined as meeting all the following criteria: 1) Clinical Global Impression of Improvement (CGI-I) ≥ 5 (minimally worse), AND an increase to score of >4 and absolute increase of ≥ 2 on the individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content); or an increase to score >4 and absolute increase of ≥ 4 on the combined 4 PANSS items on any of these PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) OR 2) Hospitalization due to worsening of psychotic symptoms, but excluding hospitalization for psychosocial reasons, OR 3) CGI-SS score of 4 (severely suicidal) or 5 (attempted suicide) on Part 1 and/or 6 (much worse) or 7 (very much worse) on Part 2, OR 4) Violent behavior resulting in clinically relevant self-injury, injury to another person, or property damage.
Time Frame	Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48,52, and Last visit (upto 4 weeks ± 3 days after completion or withdrawal)

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of participants evaluated at the specified trial week.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Week 2 (N=1028)	0.49 0%
Week 4 (N=1049)	0.48 0%
Week 8 (N=1011)	0.79 0.1%
Week 12 (N=988)	1.52 0.1%
Week 16 (N=948)	0.84 0.1%
Week 20 (N=920)	1.09 0.1%
Week 24 (N=883)	0.45 0%
Week 28 (N=857)	0.58 0.1%
Week 32 (N=838)	0.36 0%
Week 36 (N=814)	0.25 0%
Week 40 (N=808)	0.25 0%
Week 44 (N=783)	0.26 0%
Week 48 (N=750)	0.27 0%
Week 52 (N=668)	0.30 0%
Last visit (N=1079)	4.17 0.4%
Overall (N=1079)	8.25 0.8%

3. Secondary Outcome

Title	Percentage of Participants Achieving Remission.
Description	Remission is defined as a score of ≤ 3 on each of the following specific PANSS items, maintained for a period of six months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/posturing, blunted affect, social withdrawal, and lack of spontaneity.
Time Frame	Overall remission from Weeks 2,4,8,12,16,20,24,28,32,36,40,44,48 and 52

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of participants evaluated at the specified trial week.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Number [Percentage of participants]	51.7 4.8%

4. Secondary Outcome

Title	Percentage of Participants Stable at Baseline and Remaining Stable at Week 28.
Description	"Stable" was defined as meeting all of the following criteria: Outpatient status; PANSS total score ≤ 80; Lack of specific psychotic symptoms on the PANSS as measured by a score of ≤ 4 on each of the following items (possible scores of 1 to 7 for each item): 1) conceptual disorganization 2) suspiciousness 3) hallucinatory behavior 4) unusual thought content; Clinical Global Impression of Severity (CGI-S) ≤ 4 (moderately ill); and Clinical Global Impression for Severity of Suicidality (CGI-SS) ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2. The percentage of stable participants at baseline who remain stable at Week 28 is described here.
Time Frame	Baseline to Week 28

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. N defines number of stable participants at baseline who were evaluated at the specified trial week.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Baseline (N=1075)	100 9.3%
Week 28 (N=854)	98.95 9.2%

5. Secondary Outcome

Title	Percentage of Participants With Time to First Exacerbation of Psychotic Symptoms/Impending Relapse.
Description	Participants who first time meet relapse criteria were considered as having an event at date of exacerbation of psychotic symptoms/impending relapse. Time to first event was calculated as the earliest date of meeting one of relapse criteria. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed had available assessments for evaluation of exacerbation of psychotic symptoms/impending relapse.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1079
Number [Percentage of participants]	8.2 0.8%

6. Secondary Outcome

Title	Mean Change From Baseline to Endpoint (Last Visit) in Positive and Negative Syndrome Scale (PANSS) Total Score.
Description	PANSS total score (range 30-210) is the sum of the rating scores for 7 positive scale items, 7 negative scale items and 16 general psychopathology scale items from the PANSS scale. PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.
Time Frame	Baseline, Weeks 12, 24, 52 and last visit

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Week 12 (N=987)	-1.69 (6.21)
Week 24 (N=882)	-2.55 (7.08)
Week 52 (N=669)	-3.55 (7.75)
Last visit (N=1078)	-1.72 (10.21)

7. Secondary Outcome

Title	Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score.
Description	To assess CGI-S, the rater or physician will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices include: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
Time Frame	Baseline, Weeks 12, 24, 52 and last visit

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Week 12 (N=987)	-0.11 (0.52)
Week 24 (N=883)	-0.17 (0.53)
Week 52 (N=668)	-0.24 (0.56)
Last visit (N=1079)	-0.14 (0.70)

8. Secondary Outcome

Title	Mean Change From Baseline to Endpoint in PANSS Positive and Negative Subscales.
Description	PANSS positive subscale score (range 7-49) is the sum of the rating scores for the 7 positive scale items from the PANSS scale. Positive subscale consists of 7 positive symptom constructs: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). PANSS negative subscale score (range 7-49) is the sum of the rating scores for the 7 negative scale items from the PANSS scale. Negative subscale consists of 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive pathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking). The severity of each scale is rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms.
Time Frame	Baseline, Weeks 12, 24, 52 and last visit

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Week 12 positive subscale score (N=987)	-0.42 (2.11)
Week 24 positive subscale score (N=882)	-0.68 (2.26)
Week 52 positive subscale score (N=669)	-1.04 (2.53)
Last visit positive subscale score (N=1078)	-0.49 (3.38)
Week 12 negative subscale score (N=987)	-0.40 (2.40)
Week 24 negative subscale score (N=882)	-0.53 (2.52)
Week 52 negative subscale score (N=669)	-0.80 (2.94)
Last visit negative subscale score (N=1078)	-0.46 (3.19)

9. Secondary Outcome

Title	Mean Clinical Global Impression of Improvement (CGI-I) Score.
Description	To assess CGI-I the rater or physician will rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses will be compared to the participants condition at baseline. Response choices include: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Time Frame	Weeks 2, 4, 12, 24, 52 and last visit

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included. Number of participants analyzed with baseline or at least one postbaseline assessment are included here.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Baseline (N=1081)	3.48 (0.82)
Week 2 (N=1026)	3.52 (0.85)
Week 4 (N=1049)	3.49 (0.86)
Week 12 (N=987)	3.42 (0.92)
Week 24 (N=882)	3.33 (0.98)
Week 52 (N=669)	3.25 (0.99)
Last visit (N=1079)	3.35 (1.10)

10. Secondary Outcome

Title	Percentage of Participants Who Discontinued Due to All Causes.
Description	Participants who discontinued due to any cause were noted. Limited concurrent treatment with oral aripiprazole was permitted as rescue therapy.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who entered Phase 3 and have at least one post-baseline efficacy evaluation in Phase 3 are included.

Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
Measure Participants	1081
Number [Percentage of participants]	20.6 1.9%

Adverse Events

Time Frame	Phase 3 Week 1 to Week 52/Early termination.
Adverse Event Reporting Description	All participants who had received at least one dose of aripiprazole IM depot were included in safety analysis.
Arm/Group Title	Aripiprazole 400/300 mg IM Depot
Arm/Group Description	Participants received open-label aripiprazole 400/300 mg IM depot into gluteal muscle every 4 weeks for a maximum of 52 weeks. Flexible dosing with apipiprazole 300 mg and 400 mg is permitted in order to maximize retention of participants. Partipants also received supplemental oral aripiprazole (10 mg to 20 mg daily) for the first two weeks to maintain therapeutic plasma concentrations.
All Cause Mortality
	Aripiprazole 400/300 mg IM Depot
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aripiprazole 400/300 mg IM Depot
	Affected / at Risk (%)	# Events
Total	95/1081 (8.8%)
Blood and lymphatic system disorders
Anaemia	1/1081 (0.1%)
Cardiac disorders
Atrial fibrillation	1/1081 (0.1%)
Cardiac arrest	1/1081 (0.1%)
Cardiac failure	1/1081 (0.1%)
Cardiac failure acute	1/1081 (0.1%)
Cardio-respiratory arrest	1/1081 (0.1%)
Myocardial infarction	2/1081 (0.2%)
Eye disorders
Open angle glaucoma	1/1081 (0.1%)
Uveitis	1/1081 (0.1%)
Gastrointestinal disorders
Dyspepsia	1/1081 (0.1%)
Oesophageal varices haemorrhage	1/1081 (0.1%)
Pancreatitis acute	1/1081 (0.1%)
Stomach mass	1/1081 (0.1%)
General disorders
Facial pain	1/1081 (0.1%)
Sudden death	1/1081 (0.1%)
Hepatobiliary disorders
Bile duct stone	1/1081 (0.1%)
Cholelithiasis	2/1081 (0.2%)
Infections and infestations
Bronchitis	2/1081 (0.2%)
Cellulitis	2/1081 (0.2%)
Gangrene	1/1081 (0.1%)
Genital candidiasis	1/1081 (0.1%)
Hepatitis viral	1/1081 (0.1%)
Influenza	1/1081 (0.1%)
Pilonidal cyst	1/1081 (0.1%)
Pneumonia	4/1081 (0.4%)
Respiratory tract infection	1/1081 (0.1%)
Syphilis	1/1081 (0.1%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/1081 (0.1%)
Concussion	1/1081 (0.1%)
Hand fracture	1/1081 (0.1%)
Intentional overdose	2/1081 (0.2%)
Multiple injuries	1/1081 (0.1%)
Investigations
Liver function test abnormal	1/1081 (0.1%)
Metabolism and nutrition disorders
Dehydration	2/1081 (0.2%)
Hypoglycaemia	1/1081 (0.1%)
Hypovolaemia	1/1081 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/1081 (0.1%)
Breast cancer recurrent	1/1081 (0.1%)
Haemangioma of liver	1/1081 (0.1%)
Non-small cell lung cancer metastatic	1/1081 (0.1%)
Rectal cancer metastatic	1/1081 (0.1%)
Tongue neoplasm	1/1081 (0.1%)
Nervous system disorders
Convulsion	1/1081 (0.1%)
Loss of consciousness	1/1081 (0.1%)
Ruptured cerebral aneurysm	1/1081 (0.1%)
Tremor	1/1081 (0.1%)
Psychiatric disorders
Adjustment disorder	1/1081 (0.1%)
Anxiety	1/1081 (0.1%)
Depression	1/1081 (0.1%)
Hallucination	1/1081 (0.1%)
Hallucination, auditory	2/1081 (0.2%)
Homicidal ideation	1/1081 (0.1%)
Psychotic disorder	15/1081 (1.4%)
Schizoaffective disorder	1/1081 (0.1%)
Schizophrenia	21/1081 (1.9%)
Schizophrenia, paranoid type	5/1081 (0.5%)
Suicidal ideation	2/1081 (0.2%)
Suicide attempt	3/1081 (0.3%)
Reproductive system and breast disorders
Menorrhagia	1/1081 (0.1%)
Ovarian cyst	1/1081 (0.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/1081 (0.1%)
Asthma	1/1081 (0.1%)
Chronic obstructive pulmonary disease	2/1081 (0.2%)
Pneumothorax	1/1081 (0.1%)
Vascular disorders
Arteriosclerosis	1/1081 (0.1%)
Hypertension	1/1081 (0.1%)
Hypotension	1/1081 (0.1%)
Other (Not Including Serious) Adverse Events
	Aripiprazole 400/300 mg IM Depot
	Affected / at Risk (%)	# Events
Total	254/1081 (23.5%)
Infections and infestations
Nasopharyngitis	76/1081 (7%)
Nervous system disorders
Headache	82/1081 (7.6%)
Psychiatric disorders
Anxiety	73/1081 (6.8%)
Insomnia	71/1081 (6.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.