ASPIRE: An Open-Label, Multicenter, Rollover, Long-term Study of Aripiprazole Intramuscular Depot in Participants With Schizophrenia

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01129882
• Collaborator: (none)
• Enrollment: 709
• Locations: 157
• Arm: 1
• Actual Duration (Months): 101.4
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of this study was to continue to provide aripiprazole intramuscular (IM) depot treatment (400 milligrams [mg] or 300 mg) to participants with schizophrenia completing the 52-week, open-label safety and tolerability Study 31-08-248. In addition, the secondary objective was to collect additional long-term safety data on aripiprazole IM depot treatment.

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

Detailed Description

This was an open-label study that enrolled participants with schizophrenia who had completed the 52-week, open-label safety and tolerability Study 31-08-248 and continued to provide aripiprazole IM depot treatment.

Participants received this treatment until aripiprazole IM Depot was commercially available in any dosage (including generic formulations) in the country where the study was being conducted or the commercial availability of aripiprazole IM Depot was terminated by the sponsor, or until the study completion date of 06 Dec 2018 was reached.

Eligible participants entered this study at the end of treatment visit (Week 52) of Study 31-08-248. Participants continued to receive aripiprazole IM depot every month (study months were every 4 weeks, which were defined as 28 [-2/+10] days) as a continuation of their previous monthly dose in Study 31-08-248.

Study Design

• Study Type: Interventional
• Actual Enrollment: 709 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Rollover, Long-term Study of Aripiprazole Intramuscular Depot in Patients With Schizophrenia
• Actual Study Start Date: Jun 24, 2010
• Actual Primary Completion Date: Dec 6, 2018
• Actual Study Completion Date: Dec 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole IM depot Active treatment of monthly doses of aripiprazole IM depot (300 mg or 400 mg)	Drug: Aripiprazole; Aripiprazole IM depot - 300 mg or 400 mg

Outcome Measures

Primary Outcome Measures

1. Number Of Participants Reporting Severe Treatment-Emergent Adverse Events (TEAE) [Baseline to Month 97 (+/- 3 days)]

   A TEAE was defined as an AE that started after start of investigational medicinal product (IMP) treatment or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption, or reduction of IMP. A severe AE was one that caused inability to work or perform normal daily activity. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Secondary Outcome Measures

1. Mean Change In Clinical Global Impression-Severity (CGI-S) of Illness Scale Score From Baseline To Last Visit [Baseline, Month 91]

   The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices included: 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 patients. The Last Visit was defined as the last available post-baseline evaluation. A decrease in the CGI-S score indicated disease stability or improvement.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants with a current diagnosis of schizophrenia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, who completed the open-label extension Study 248 (completed Study 248 study completion visit, Week 52).

• Participants who, in the investigator's judgment, may benefit from continued participation in an aripiprazole IM Depot study.

• The baseline visit for Study 270 (which is the Week 52 visit of Study 248) and the first injection for Study 270 must occur within 4 weeks (which was defined as 28 [-2/+10] days) of the last injection in Study 248.

• Participants who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by an Independent Review Board/Independent Ethics Committee (IRB/IEC), prior to the initiation of any protocol-required procedures.

• Participants able to understand the nature of the study and follow protocol requirements and who can read and understand the written word in order to complete patient-reported outcomes measures.

• Outpatient status.

Exclusion Criteria:

• Participants 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.

• Participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

• Participants who currently meet DSM-IV-TR criteria for substance dependence, including alcohol and benzodiazepines, but excluding caffeine and nicotine.

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

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

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

• Electroconvulsive therapy within 180 days prior to entry.

• Any participant who requires or may need any other antipsychotic medications during the course of the study.

• Aripiprazole IM Depot (including generic formulation) is commercially available in the participant's country.

• Other protocol specific inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bellevue	California	United States	98007
2		Garden Grove	California	United States	92845
3		Glendale	California	United States	91204
4		Glendale	California	United States	91206
5		Imperial	California	United States	92251
6		Los Angeles	California	United States	90024
7		National City	California	United States	91950
8		National City	California	United States
9		Orange	California	United States	92868
10		Pasadena	California	United States	91107
11		Pico Rivera	California	United States	90660
12		Pico Rivera	California	United States
13		San Bernardino	California	United States	92408-3304
14		San Diego	California	United States
15		Sherman Oaks	California	United States	91403
16		Norwalk	Connecticut	United States	06851
17		Washington	District of Columbia	United States	20016
18		Washington	District of Columbia	United States
19		Bradenton	Florida	United States
20		Doral	Florida	United States
21		Hialeah	Florida	United States	33016
22		Homestead	Florida	United States	33030
23		Orange City	Florida	United States	32763
24		Tampa	Florida	United States	33613
25		Chicago	Illinois	United States	60612
26		Chicago	Illinois	United States	60640
27		Oak Brook	Illinois	United States	60523
28		Indianapolis	Indiana	United States	46222
29		Shreveport	Louisiana	United States	71101
30		Flowood	Mississippi	United States	39232
31		Saint Louis	Missouri	United States	63109
32		North Platte	Nebraska	United States	69101
33		Buffalo	New York	United States	14215
34		New York	New York	United States	10035
35		Queens	New York	United States
36		Rochester	New York	United States	14615
37		Charlotte	North Carolina	United States	28204
38		Akron	Ohio	United States
39		Canton	Ohio	United States	44718
40		Toledo	Ohio	United States	43609
41		Oklahoma City	Oklahoma	United States	73112
42		Allentown	Pennsylvania	United States	18104
43		Jenkintown	Pennsylvania	United States	19046
44		Sellersville	Pennsylvania	United States	18960
45		Charleston	South Carolina	United States	29401
46		Memphis	Tennessee	United States	38119
47		Austin	Texas	United States	78731
48		Austin	Texas	United States	78754
49		DeSoto	Texas	United States	75115
50		Richmond	Virginia	United States	23230
51		Bothell	Washington	United States	98011
52		Milwaukee	Wisconsin	United States	53226
53		Buenos Aires		Argentina	1900
54		Buenos Aires		Argentina	C1058AAH
55		Buenos Aires		Argentina	C1405BOA
56		Buenos Aires		Argentina	C1425AHQ
57		Mendoza		Argentina	M5500HYF
58		Epping	Victoria	Australia	3076
59		Frankston	Victoria	Australia	3199
60		Fremantle	Western Australia	Australia	6959
61		Bourgas		Bulgaria	8000
62		Lovech		Bulgaria	5500
63		Pazardzhik		Bulgaria	4400
64		Pleven		Bulgaria	5800
65		Plovdiv		Bulgaria	4002
66		Plovdiv		Bulgaria
67		Radnevo		Bulgaria	6260
68		Rousse		Bulgaria	7003
69		Sofia		Bulgaria	1113
70		Sofia		Bulgaria	1431
71		Sofia		Bulgaria	1632
72		Tserova Koria		Bulgaria
73		Varna		Bulgaria	9001
74		Varna		Bulgaria
75		Santiago		Chile	7500710
76		Santiago		Chile	7510186
77		Santiago		Chile	7580307
78		Santiago		Chile	8330838
79		Santiago		Chile	8780000
80		Santiago		Chile	8900085
81		Temuco		Chile	4781151
82		Valdivia		Chile	5090145
83		Zagreb		Croatia	10000
84		Zagreb		Croatia	10090
85		Zagreb		Croatia
86		Tallinn		Estonia	10614
87		Tallinn		Estonia	10617
88		Tartu		Estonia	50417
89		Tartu		Estonia
90		Viljandi		Estonia	71024
91		Helsinki		Finland	250
92		Baja		Hungary	6500
93		Balassagyarmat		Hungary	2660
94		Gyõr		Hungary	9023
95		Ahmedabad	Gujarat	India	380006
96		Mangalore	Karnataka	India	575018
97		Bangalore		India
98		Chennai		India
99		Kanpur		India	208005
100		Pune		India	411004
101		Tirupati		India	517507
102		Daejeon		Korea, Republic of	301-721
103		Gwangju		Korea, Republic of	501-757
104		Incheon		Korea, Republic of	400-711
105		Seoul		Korea, Republic of	110-744
106		Ipoh		Malaysia
107		Kajang		Malaysia
108		Kuala Lumpur		Malaysia	56000
109		Kuala Lumpur		Malaysia	59100
110		Guadalajara	Jalisco	Mexico	44280
111		Monterrey	Nuevo León	Mexico	64040
112		Culiacan	Sinaloa	Mexico	80020
113		Mexico		Mexico	7760
114		San Luis Potosí		Mexico	78218
115		Mandaluyong City	NCR	Philippines	1553
116		Iloilo City	Western Visayas	Philippines	5000
117		Mariveles		Philippines
118		Belchatow		Poland	97-400
119		Bialystok		Poland	15-879
120		Bydgoszcz		Poland	85096
121		Choroszcz		Poland	16-070
122		Krakow		Poland	31-501
123		Leszno		Poland	64-100
124		Sosnowiec		Poland	41-200
125		Wroclaw		Poland	50-227
126		San Juan		Puerto Rico	00918
127		Arad		Romania	310022
128		Bucharest		Romania	41914
129		Cluj-Napoca		Romania	400012
130		Craiova		Romania	200620
131		Oradea		Romania	410163
132		Pitesti		Romania	110069
133		Leningrad		Russian Federation
134		Lipetsk		Russian Federation	398007
135		Moscow		Russian Federation	115522
136		Moscow		Russian Federation	127083
137		Nizhny Novgorod		Russian Federation	603152
138		Nizhny Novgorod		Russian Federation	603155
139		Smolensk		Russian Federation
140		St. Petersburg		Russian Federation	190121
141		St. Petersburg		Russian Federation	192019
142		Belgrade		Serbia	11000
143		Kragujevac		Serbia	34000
144		Bardejov		Slovakia
145		Kosice		Slovakia	041 90
146		Liptovsky Mikulas		Slovakia	3101
147		Prešov		Slovakia
148		Rimavská Sobota		Slovakia
149		Cape Town	Western Province	South Africa	7530
150		Bellville		South Africa	7530
151		Pretoria West		South Africa	1
152		Barcelona		Spain	08006
153		Barcelona		Spain	8036
154		Hospitalet de Llobregat		Spain
155		Tainan		Taiwan	704
156		Taipei City		Taiwan	110
157		Chiang Mai		Thailand

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 12, 2018
• Study Protocol - Jul 8, 2015

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT01129882
• Other Study ID Numbers: 31-10-270
• First Posted: May 25, 2010
• Last Update Posted: Jan 6, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Schizophrenia
• Additional relevant MeSH terms: Schizophrenia; Aripiprazole

Study Results

Participant Flow

Pre-assignment Detail	Participants with a current diagnosis of schizophrenia, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, who completed the open-label extension Study 31-08-248 (NCT00731549) (completed Study 248 Study Completion visit, Week 52).

Arm/Group Title	Aripiprazole IM Depot
Arm/Group Description	Monthly dose of 400 milligrams (mg) or 300 mg aripiprazole intramuscular (IM) depot to adult participants with schizophrenia who completed aripiprazole IM depot treatment in Study 31-08-248.
Period Title: Overall Study
STARTED	709
Received at Least 1 Dose of Study Drug	709
COMPLETED	431
NOT COMPLETED	278

Baseline Characteristics

Arm/Group Title	Aripiprazole IM Depot
Arm/Group Description	Monthly dose of 400 milligrams (mg) or 300 mg aripiprazole intramuscular (IM) depot to adult participants with schizophrenia who completed aripiprazole IM depot treatment in Study 31-08-248.
Overall Participants	709
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	709 100%
>=65 years	0 0%
Age (Years) [Mean (Standard Deviation) ]
Age (years)	41.9 (10.4)
Sex: Female, Male (Count of Participants)
Female	295 41.6%
Male	414 58.4%
Race/Ethnicity, Customized (Count of Participants)
White	464 65.4%
Black or African American	78 11%
American Indian or Alaska Native	1 0.1%
Asian	107 15.1%
Native Hawaiian or Other Pacific Islander	1 0.1%
Other	58 8.2%

Outcome Measures

1. Primary Outcome

Title	Number Of Participants Reporting Severe Treatment-Emergent Adverse Events (TEAE)
Description	A TEAE was defined as an AE that started after start of investigational medicinal product (IMP) treatment or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption, or reduction of IMP. A severe AE was one that caused inability to work or perform normal daily activity. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	Baseline to Month 97 (+/- 3 days)

Outcome Measure Data

Analysis Population Description

The Safety Sample includes all participants who received at least 1 dose of open-label aripiprazole IM depot.

Arm/Group Title	Aripiprazole IM Depot
Arm/Group Description	Monthly dose of 400 milligrams (mg) or 300 mg aripiprazole intramuscular (IM) depot to adult participants with schizophrenia who completed aripiprazole IM depot treatment in Study 31-08-248.
Measure Participants	709
Number [participants]	50 7.1%

2. Secondary Outcome

Title	Mean Change In Clinical Global Impression-Severity (CGI-S) of Illness Scale Score From Baseline To Last Visit
Description	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the rater or investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" Response choices included: 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 patients. The Last Visit was defined as the last available post-baseline evaluation. A decrease in the CGI-S score indicated disease stability or improvement.
Time Frame	Baseline, Month 91

Outcome Measure Data

Analysis Population Description

The Efficacy Sample comprises those participants who entered the trial and had at least 1 post-baseline efficacy evaluation.

Arm/Group Title	Aripiprazole IM Depot
Arm/Group Description	Monthly dose of 400 milligrams (mg) or 300 mg aripiprazole intramuscular (IM) depot to adult participants with schizophrenia who completed aripiprazole IM depot treatment in Study 31-08-248.
Measure Participants	703
Mean (Standard Deviation) [units on a scale]	-0.14 (0.69)

Adverse Events

Time Frame	Baseline to Month 97 (+/- 3 days)
Adverse Event Reporting Description	The Safety Sample comprised all participants who received at least 1 dose of open-label aripiprazole IM depot.
Arm/Group Title	Aripiprazole IM Depot
Arm/Group Description	Monthly dose of 400 milligrams (mg) or 300 mg aripiprazole intramuscular (IM) depot to adult participants with schizophrenia who completed aripiprazole IM depot treatment in Study 31-08-248.
All Cause Mortality
	Aripiprazole IM Depot
	Affected / at Risk (%)	# Events
Total	6/709 (0.8%)
Serious Adverse Events
	Aripiprazole IM Depot
	Affected / at Risk (%)	# Events
Total	62/709 (8.7%)
Blood and lymphatic system disorders
Thrombocytopenia	1/709 (0.1%)	1
Anaemia	1/709 (0.1%)	1
Cardiac disorders
Supraventricular Tachycardia	1/709 (0.1%)	1
Acute Myocardial Infarction	1/709 (0.1%)	1
Arteriospasm Coronary	1/709 (0.1%)	1
Myocardial Ischaemia	1/709 (0.1%)	1
Cardio-Respiratory Arrest	1/709 (0.1%)	1
Congenital, familial and genetic disorders
Vitello-Intestinal Duct Remnant	1/709 (0.1%)	1
General disorders
Death	1/709 (0.1%)	1
Hepatobiliary disorders
Hepatic Failure	1/709 (0.1%)	1
Autoimmune Hepatitis	1/709 (0.1%)	1
Hepatic Cirrhosis	1/709 (0.1%)	1
Infections and infestations
Pneumonia Bacterial	1/709 (0.1%)	1
Pneumonia	3/709 (0.4%)	3
Oesophageal Candidiasis	1/709 (0.1%)	1
Influenza	1/709 (0.1%)	1
Urinary Tract Infection	1/709 (0.1%)	1
Pulmonary Tuberculosis	1/709 (0.1%)	1
Infection	1/709 (0.1%)	1
Erysipelas	1/709 (0.1%)	1
Abscess Jaw	1/709 (0.1%)	1
Abdominal Abscess	1/709 (0.1%)	1
Abdominal Infection	1/709 (0.1%)	1
Dengue Fever	1/709 (0.1%)	1
Bacteraemia	1/709 (0.1%)	1
Cellulitis	1/709 (0.1%)	1
Injury, poisoning and procedural complications
Accidental Overdose	1/709 (0.1%)	1
Gun Shot Wound	1/709 (0.1%)	1
Foot Fracture	1/709 (0.1%)	1
Road Traffic Accident	1/709 (0.1%)	1
Investigations
Hepatic Enzyme Increased	1/709 (0.1%)	1
Metabolism and nutrition disorders
Type 2 Diabetes Mellitus	1/709 (0.1%)	1
Diabetes Mellitus	1/709 (0.1%)	1
Haemosiderosis	1/709 (0.1%)	1
Musculoskeletal and connective tissue disorders
Still's Disease	1/709 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic Carcinoma Metastatic	1/709 (0.1%)	1
Breast Cancer	1/709 (0.1%)	1
Cerebellar Tumour	1/709 (0.1%)	1
Lung Adenocarcinoma	1/709 (0.1%)	1
Metastases to Liver	1/709 (0.1%)	1
Pleomorphic Adenoma	1/709 (0.1%)	1
Nervous system disorders
Presyncope	1/709 (0.1%)	1
Cerebrovascular Accident	1/709 (0.1%)	1
Thrombotic Cerebral Infarction	1/709 (0.1%)	1
Seizure	2/709 (0.3%)	2
Loss of Consciousness	1/709 (0.1%)	1
Psychiatric disorders
Psychotic Disorder	9/709 (1.3%)	9
Suicide Attempt	2/709 (0.3%)	2
Suicidal Behaviour	1/709 (0.1%)	1
Schizophrenia	14/709 (2%)	14
Insomnia	1/709 (0.1%)	1
Aggression	1/709 (0.1%)	1
Delusion	1/709 (0.1%)	1
Acute Stress Disorder	1/709 (0.1%)	1
Suicidal Ideation	1/709 (0.1%)	1
Impulse-Control Disorder	1/709 (0.1%)	1
Renal and urinary disorders
Nephrolithiasis	1/709 (0.1%)	1
Reproductive system and breast disorders
Cystocele	1/709 (0.1%)	1
Metrorrhagia	1/709 (0.1%)	1
Ovarian Cyst	1/709 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	1/709 (0.1%)	1
Pulmonary Hypertension	1/709 (0.1%)	1
Skin and subcutaneous tissue disorders
Skin Ulcer	1/709 (0.1%)	1
Dermatitis Allergic	1/709 (0.1%)	1
Social circumstances
Poor Personal Hygiene	1/709 (0.1%)	1
Vascular disorders
Hypertension	1/709 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Aripiprazole IM Depot
	Affected / at Risk (%)	# Events
Total	515/709 (72.6%)
Gastrointestinal disorders
Diarrhoea	37/709 (5.2%)	37
Infections and infestations
Influenza	48/709 (6.8%)	48
Nasopharyngitis	87/709 (12.3%)	87
Upper Respiratory Tract Infection	54/709 (7.6%)	54
Investigations
Weight Increased	81/709 (11.4%)	81
Musculoskeletal and connective tissue disorders
Back Pain	42/709 (5.9%)	42
Nervous system disorders
Headache	77/709 (10.9%)	77
Psychiatric disorders
Anxiety	44/709 (6.2%)	44
Insomnia	70/709 (9.9%)	70

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.