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: NCT00705783
• Collaborator: (none)
• Enrollment: 843
• Locations: 110
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the trial was to evaluate the efficacy, safety, and tolerability of an intramuscular depot formulation of aripiprazole as maintenance treatment in patients with schizophrenia.

The trial was designed into 4 treatment phases. Phase 1 was designed to allow for a patient to be converted from their current antipsychotic treatment to oral non-generic aripiprazole monotherapy (oral conversion phase from 4 to 6 weeks). During Phase 2, the patient was stabilized on oral non-generic aripiprazole monotherapy (oral stabilization phase from a minimum of 4 weeks to a maximum of 12 weeks). Once the patient was stabilized in Phase 2, they entered Phase 3, the single-blind intramuscular (IM) depot aripiprazole stabilization phase. The goal of the phase was to stabilize the patient on the IM depot aripiprazole formulation for a minimum of 12 weeks to a maximum of 36 weeks. When the patient was stabilized, they were eligible to be randomized into the double-blind IM depot maintenance phase (Phase 4). During Phase 4, the patient was assessed for exacerbation of psychotic symptoms and/or impending relapse for up to 52 weeks.

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

Detailed Description

This was a randomized, double-blind, placebo-controlled study consisting of a screening phase and 4 treatment phases. Eligibility was determined during a screening phase of 2 to 42 days. Patients receiving oral treatment with an antipsychotic other than non-generic aripiprazole entered Phase 1. Patients with a lapse in aripiprazole or other antipsychotic treatment at the time of study entry ("lapse" defined as > 3 consecutive days without medication) entered directly into Phase 2. During Phase 1 (oral conversion), patients were cross-titrated during weekly visits from other antipsychotics to oral non-generic aripiprazole monotherapy over a minimum of 4 weeks and a maximum of 6 weeks. During Phase 2 (a minimum of 4 weeks and a maximum of 12 weeks in duration), patients were assessed bi-weekly and stabilized on an oral dose of aripiprazole ranging from 10 mg to 30 mg daily. After stability criteria were met in Phase 2, patients entered the single-blind aripiprazole intramuscular (IM) depot stabilization phase, Phase 3. In Phase 3, patients were stabilized on aripiprazole IM depot for 12 consecutive weeks. Once the patient met the stability criteria, they were eligible to be randomized into the double-blind phase, Phase 4. Patients were randomized in a 2:1 ratio (aripiprazole IM depot vs placebo IM depot) stratified by region and last aripiprazole IM depot injection dose level in Phase 3. During Phase 4, patients were assessed for impending relapse/exacerbation of psychotic symptoms. If a patient was identified with impending relapse/exacerbation of psychotic symptoms, they were withdrawn from the trial and given the opportunity to enroll into an open-label aripiprazole IM depot trial, 31-08-248. Patients that completed Phase 4 (up to and including Week 52) had the option to enroll into an open-label aripiprazole IM depot trial, 31-08-248 (NCT00731549).

Study Design

• Study Type: Interventional
• Actual Enrollment: 843 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of an Intramuscular Depot Formulation of Aripiprazole as Maintenance Treatment in Patients With Schizophrenia
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole depot Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Drug: Aripiprazole depot; Aripiprazole depot was supplied in 400 mg lyophilized vials. Patients received aripiprazole 300 mg if they were unable to tolerate aripiprazole 400 mg.; Other Names: Abilify
Placebo Comparator: Placebo depot Patients received placebo intramuscularly every 28 days for 52 weeks.	Drug: Placebo depot; Placebo depot was supplied in 400 mg lyophilized vials.

Outcome Measures

Primary Outcome Measures

1. Time to Exacerbation of Psychotic Symptoms/Impending Relapse [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   A patient experienced an exacerbation of psychotic symptoms/impending relapse if they met any of the following 4 criteria. 1) Clinical Global Impression of Improvement score ≥ 5 and either an increase on any of the following Positive and Negative Syndrome Scale (PANSS) items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) to a score > 4 with an increase of ≥ 2 on that item since randomization or an increase on any of the same PANSS items to a score > 4 and an increase of ≥ 4 on the same combined PANSS items since randomization, 2) Hospitalization due to worsening of psychotic symptoms, 3) Clinical Global Impression of Severity of Suicide (CGI-SS) score of 4 or 5 on Part 1 and/or 6 or 7 on Part 2, or 4) Violent behavior resulting in clinically significant self-injury, injury to another person, or property damage.

Secondary Outcome Measures

1. Percentage of Patients Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   This is the key secondary Outcome Measure.

2. Percentage of Responders [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   A patient was considered to be a responder if all of the following criteria were met. 1) Outpatient status, 2) PANSS total score ≤ 80, 3) 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): Conceptual disorganization, suspiciousness, hallucinatory behavior, unusual thought content, and 4) Clinical Global Impression of Severity of Illness (CGI-S) ≤ 4 (moderately ill) and 5) CGI-SS ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2.

3. Percentage of Patients Achieving Remission [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   A patient was considered to have achieved remission if they had a score of ≤ 3 on each of the following PANSS items, maintained for a period of 6 months: Delusions (P1), unusual thought content (G9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerisms/posturing (G5), blunted affect (N1), social withdrawal (N4), and lack of spontaneity (N6).

4. Mean Change From Baseline in the PANSS Total Score [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   The PANSS consists of 3 subscales (Positive Subscale, 7 constructs, scores ranged from 7-49, Negative Subscale, 7 constructs, scores ranged from 7-49, General Psychopathology Subscale, 16 constructs, scores ranged from 16-112) containing a total of 30 symptom constructs. For each symptom construct, severity was 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. The PANSS total score ranged from 30-210 with a higher score indicating more severe symptoms. A negative change score indicates improvement.

5. Mean Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   The severity of illness for each patient was rated using the CGI-S. 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 CGI-S score ranged from 0-7 with a higher score indicating greater illness. A negative change score indicates improvement.

6. Mean Change From Baseline in the PANSS Positive Subscale Score [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   The PANSS Positive Subscale consists of 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). For each symptom construct, severity was 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. Scores on each subscale ranged from 7-49 with a higher score indicating more severe symptoms. A negative change score indicates improvement.

7. Mean Change From Baseline in the PANSS Negative Subscale Score [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   The PANSS Negative Subscale consists of 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive pathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking). For each symptom construct, severity was 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. Scores on each subscale ranged from 7-49 with a higher score indicating more severe symptoms. A negative change score indicates improvement.

8. Mean Clinical Global Impression-Improvement (CGI-I) Score [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   The efficacy of the study medication was rated for each patient using the CGI-I scale. The rater or investigator rated the patient's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the patient's condition at Baseline. Response choices included: 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. The CGI-I score ranged from 0-7 with a higher score indicating less improvement/worsening.

9. Time to Discontinuation [Baseline of the depot maintenance phase to the end of the study (Week 52)]

   Time to discontinuation was defined as the date of randomization to the date of study discontinuation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 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 required by the Institutional Review Board/Institutional Ethics Committee [IRB/IEC]), prior to the initiation of any protocol-required procedures.

• Male and female subjects 18 to 60 years of age, inclusive, at time of informed consent.

• Subjects with a current diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition text revision (DSM-IV-TR) criteria and a history of the illness for at least 3 years prior to screening.

• 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, or 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 2 positive drug screens for cocaine.

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

• Subjects with uncontrolled thyroid function abnormalities.

• Subjects with a history of seizures, neuroleptic malignant syndrome, clinically significant tardive dyskinesia, or other medical condition that would expose them to undue risk or interfere with study assessments.

• Subjects who are involuntary incarcerated.

• Subjects who have used an investigational agent within 30 days of screening or prior participation in a clinical study with aripiprazole IM depot.

• Subjects with clinically significant abnormalities in laboratory test results, vital signs, or ECG results; and subjects hospitalized for more than 30 days in the 90 days prior to Phase 1.

• Subjects who fail to wash-out from prohibited concomitant medications, including the use of CYP2D6 or CYP3A4 inhibitors or CYP3A4 inducers, antipsychotics, antidepressants (including monoamine oxidase inhibitors [MAOI}), and mood stabilizers during screening and/or Phase 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Otsuka Investigational Site	Chandler	Arizona	United States	85226
2	Otsuka Investigational Site	Anaheim	California	United States	92805
3	Otsuka Investigational Site	National City	California	United States	91950
4	Otsuka Investigational Site	Oceanside	California	United States	92056
5	Otsuka Investigational Site	San Diego	California	United States	92123
6	Otsuka Investigational Site	Santa Ana	California	United States	92701
7	Otsuka Investigational Site	Highlands Ranch	Colorado	United States	80130
8	Otsuka Investigational Site	Norwalk	Connecticut	United States	06851
9	Otsuka Investigational Site	Altamonte Springs	Florida	United States	32701
10	Otsuka Investigational Site	Bradenton	Florida	United States	34208
11	Otsuka Investigational Site	Hollywood	Florida	United States	33021
12	Otsuka Investigational Site	Maitland	Florida	United States	32751
13	Otsuka Investigational Site	Miami	Florida	United States	33135
14	Otsuka Investigational Site	North Miami	Florida	United States	33161
15	Otsuka Investigational Site	Orange City	Florida	United States	32763
16	Otsuka Investigational Site	Tampa	Florida	United States	33613
17	Otsuka Investigational Site	Atlanta	Georgia	United States	30328
18	Otsuka Investigational Site	Hoffman Estates	Illinois	United States	60169
19	Otsuka Investigational Site	Munster	Indiana	United States	46321
20	Otsuka Investigational Site	Baton Rouge	Louisiana	United States	70808
21	Otsuka Investigational Site	Baton Rouge	Louisiana	United States	70809
22	Otsuka Investigational Site	Lake Charles	Louisiana	United States	70601
23	Otsuka Investigational Site	New Orleans	Louisiana	United States	70115
24	Otsuka Investigational Site	Columbia	Maryland	United States	21045
25	Otsuka Investigational Site	Flowood	Mississippi	United States	39232
26	Otsuka Investigational Site	St. Louis	Missouri	United States	63118
27	Otsuka Investigational Site	North Platte	Nebraska	United States	69101
28	Otsuka Investigational Site	Albuquerque	New Mexico	United States	87131
29	Otsuka Investigational Site	Buffalo	New York	United States	14215
30	Otsuka Investigational Site	Cedarhurst	New York	United States	11516
31	Otsuka Investigational Site	Elmsford	New York	United States	10523
32	Otsuka Investigational Site	Holliswood	New York	United States	11423
33	Otsuka Investigational Site	Jamaica	New York	United States	11418
34	Otsuka Investigational Site	Staten Island	New York	United States	10305
35	Otsuka Investigational Site	Cleveland	Ohio	United States	44109
36	Otsuka Investigational Site	Oklahoma City	Oklahoma	United States	73103
37	Otsuka Investigational Site	Philadelphia	Pennsylvania	United States	19131
38	Otsuka Investigational Site	Memphis	Tennessee	United States	38119
39	Otsuka Investigational Site	Austin	Texas	United States	78754
40	Otsuka Investigational Site	DeSoto	Texas	United States	75115
41	Otsuka Investigational Site	Bellevue	Washington	United States	98007
42	Otsuka Investigational Site	Bothell	Washington	United States	98011
43	Otsuka Investigational Site	Richland	Washington	United States	99354
44	Otsuka Investigational Site	Ciudad Autónoma de Bs. As.	Buenos Aires	Argentina	C1058AAJ
45	Otsuka Investigational Site	La Plata	Buenos Aires	Argentina	1900
46	Otsuka Investigational Site	Lanús Este	Buenos Aires	Argentina	B1834IBR
47	Otsuka Investigational Site	Pueyrredón	Cordoba	Argentina	X5004ALB
48	Otsuka Investigational Site	Rosario	Santa Fe	Argentina	2000
49	Otsuka Investigational Site	Buenos Aires		Argentina	C1405BOA
50	Otsuka Investigational Site	Buenos Aires		Argentina	C1425AHQ
51	Otsuka Investigational Site	Cordoba		Argentina	X5009BIN
52	Otsuka Investigational Site	Mendoza		Argentina	5500HYF
53	Otsuka Investigational Site	Mendoza		Argentina	5500
54	Otsuka Investigational Site	Lovech		Bulgaria	5500
55	Otsuka Investigational Site	Pleven		Bulgaria	5800
56	Otsuka Investigational Site	Plovdiv		Bulgaria	4002
57	Otsuka Investigational Site	Radnevo		Bulgaria	6260
58	Otsuka Investigational Site	Region of Veliko Tarnovo		Bulgaria	5047
59	Otsuka Investigational Site	Rousse		Bulgaria	7000
60	Otsuka Investigational Site	Sofia		Bulgaria	1113
61	Otsuka Investigational Site	Varna		Bulgaria	9010
62	Otsuka Investigational Site	Ahmedabad	Gujarat	India	380006
63	Otsuka Investigational Site	Bangalore	Karnataka	India	560010
64	Otsuka Investigational Site	Chennai	Tamil Nadu	India	600003
65	Otsuka Investigational Site	Kanpur		India	208005
66	Otsuka Investigational Site	Mangalore		India	575018
67	Otsuka Investigational Site	Pune		India	411004
68	Otsuka Investigational Site	Tirupati		India	517507
69	Otsuka Investigational Site	Cheras	Kuala Lumpur	Malaysia	56000
70	Otsuka Investigational Site	Tanjong Rambutan	Perak	Malaysia	31250
71	Otsuka Investigational Site	Kuala Lumpur	Wilayah Persekutuan	Malaysia	50603
72	Otsuka Investigational Site	Selangor		Malaysia	43000
73	Otsuka Investigational Site	Mexico	DF	Mexico	6700
74	Otsuka Investigational Site	Guadalajara	Jalisco	Mexico	44280
75	Otsuka Investigational Site	Monterrey	Nuevo León	Mexico	64040
76	Otsuka Investigational Site	Culiacan	Sinaloa	Mexico	80020
77	Otsuka Investigational Site	San Luis Potosí		Mexico	78218
78	Otsuka Investigational Site	Bataan	Central Luzon	Philippines	2105
79	Otsuka Investigational Site	Mandaluyong	NCR	Philippines	1553
80	Otsuka Investigational Site	Quezon City	NCR	Philippines	1104
81	Otsuka Investigational Site	Iloilo	Western Visayas	Philippines	5000
82	Otsuka Investigational Site	Cebu City		Philippines	6000
83	Otsuka Investigational Site	Arad		Romania	310022
84	Otsuka Investigational Site	Bucuresti		Romania	041914
85	Otsuka Investigational Site	Cluj-Napoca		Romania	400012
86	Otsuka Investigational Site	Craiova		Romania	200620
87	Otsuka Investigational Site	Oradea		Romania	410154
88	Otsuka Investigational Site	Pitesti		Romania	110069
89	Otsuka Investigational Site	Lipetsk		Russian Federation	399083
90	Otsuka Investigational Site	Moscow		Russian Federation	115409
91	Otsuka Investigational Site	Moscow		Russian Federation	115522
92	Otsuka Investigational Site	Moscow		Russian Federation	127473
93	Otsuka Investigational Site	Nizhny Novgorod		Russian Federation	603107
94	Otsuka Investigational Site	Nizhny Novgorod		Russian Federation	603155
95	Otsuka Investigational Site	Smolensk		Russian Federation	214019
96	Otsuka Investigational Site	St. Petersburg		Russian Federation	188357
97	Otsuka Investigational Site	St. Petersburg		Russian Federation	190121
98	Otsuka Investigational Site	St. Petersburg		Russian Federation	192019
99	Otsuka Investigational Site	Belgrade		Serbia	11000
100	Otsuka Investigational Site	Kragujevac		Serbia	34000
101	Otsuka Investigational Site	Kosice		Slovakia	041 90
102	Otsuka Investigational Site	Liptovský Mikuláš		Slovakia	031 23
103	Otsuka Investigational Site	Presov		Slovakia	081 81
104	Otsuka Investigational Site	Rimavská Sobota		Slovakia	979 12
105	Otsuka Investigational Site	Svidnik		Slovakia	089 01
106	Otsuka Investigational Site	Changhua		Taiwan	500
107	Otsuka Investigational Site	Hualien		Taiwan	981
108	Otsuka Investigational Site	Tainan		Taiwan	704
109	Otsuka Investigational Site	Taipei		Taiwan	110
110	Otsuka Investigational Site	Taipei		Taiwan	112

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

• Study Director: Raymond Sanchez, MD, Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT00705783
• Other Study ID Numbers: 31-07-246
• First Posted: Jun 26, 2008
• Last Update Posted: Jul 19, 2013
• Last Verified: Jun 1, 2013

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

Study Results

Participant Flow

Pre-assignment Detail	There were 4 phases in this study. In phases 1-3 (Conversion Phase, Oral Stabilization Phase, Depot Stabilization Phase), there was a single treatment group. In phase 4 (Depot Maintenance Phase), there were 2 treatment groups. All Outcome Measures were assessed in the Depot Maintenance Phase of the study.

Arm/Group Title	All Patients	Aripiprazole Depot	Placebo Depot
Arm/Group Description	During the Conversion Phase, patients were cross-titrated from other antipsychotics to oral non-generic aripiprazole monotherapy. During the Oral Stabilization Phase, patients were stabilized on an oral dose of aripiprazole ranging from 10 mg to 30 mg daily. During the Depot Stabilization Phase, patients were stabilized on aripiprazole depot.	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Period Title: Conversion Phase
STARTED	633	0	0
Received Study Medication	632	0	0
COMPLETED	500	0	0
NOT COMPLETED	133	0	0
Period Title: Conversion Phase
STARTED	710	0	0
Received Study Medication	709	0	0
COMPLETED	576	0	0
NOT COMPLETED	134	0	0
Period Title: Conversion Phase
STARTED	576	0	0
COMPLETED	403	0	0
NOT COMPLETED	173	0	0
Period Title: Conversion Phase
STARTED	0	269	134
COMPLETED	0	23	3
NOT COMPLETED	0	246	131

Baseline Characteristics

Arm/Group Title	Aripiprazole Depot	Placebo Depot	Total
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.	Total of all reporting groups
Overall Participants	269	134	403
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.1 (11.0)	41.7 (10.5)	40.6 (10.8)
Sex: Female, Male (Count of Participants)
Female	107 39.8%	55 41%	162 40.2%
Male	162 60.2%	79 59%	241 59.8%

Outcome Measures

1. Primary Outcome

Title	Time to Exacerbation of Psychotic Symptoms/Impending Relapse
Description	A patient experienced an exacerbation of psychotic symptoms/impending relapse if they met any of the following 4 criteria. 1) Clinical Global Impression of Improvement score ≥ 5 and either an increase on any of the following Positive and Negative Syndrome Scale (PANSS) items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content) to a score > 4 with an increase of ≥ 2 on that item since randomization or an increase on any of the same PANSS items to a score > 4 and an increase of ≥ 4 on the same combined PANSS items since randomization, 2) Hospitalization due to worsening of psychotic symptoms, 3) Clinical Global Impression of Severity of Suicide (CGI-SS) score of 4 or 5 on Part 1 and/or 6 or 7 on Part 2, or 4) Violent behavior resulting in clinically significant self-injury, injury to another person, or property damage.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	269	134
Median (95% Confidence Interval) [Days]	NA	209

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments	Based on 6-month IR rates of 55% for placebo and 35% for aripiprazole, sample sizes were estimated to achieve 90% power to detect a hazard ratio of 0.54 and to preserve an overall nominal alpha level of 0.05 (2-sided), allowing for 2 interim looks at 50% and 75% of events. Assuming that each subject was followed for 12 months after randomization and allowing for a 25% loss to follow-up, the projected total number of subjects to be randomly assigned to treatment in the trial was 225.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.199
	Confidence Interval	(2-Sided) 95%; 0.125 to 0.317
	Parameter Dispersion	Type: Value:
	Estimation Comments	Aripiprazole depot/placebo depot

2. Secondary Outcome

Title	Percentage of Patients Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria
Description	This is the key secondary Outcome Measure.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	269	134
Number [Percentage of patients]	10.0	39.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The alpha levels for this key secondary Outcome Measure were the same as used for the primary Outcome Measure.
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Percentage of Responders
Description	A patient was considered to be a responder if all of the following criteria were met. 1) Outpatient status, 2) PANSS total score ≤ 80, 3) 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): Conceptual disorganization, suspiciousness, hallucinatory behavior, unusual thought content, and 4) Clinical Global Impression of Severity of Illness (CGI-S) ≤ 4 (moderately ill) and 5) CGI-SS ≤ 2 (mildly suicidal) on Part 1 and ≤ 5 (minimally worsened) on Part 2.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All randomized patients. Two of the 269 patients in the ITT population did not attend the Last Visit at which this Outcome Measure was assessed and were not included in the analysis.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	267	134
Number [Percentage of patients]	87.6	56.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Percentage of Patients Achieving Remission
Description	A patient was considered to have achieved remission if they had a score of ≤ 3 on each of the following PANSS items, maintained for a period of 6 months: Delusions (P1), unusual thought content (G9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerisms/posturing (G5), blunted affect (N1), social withdrawal (N4), and lack of spontaneity (N6).
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients who stayed in Phase 4 for at least 6 months and had values for the specific PANSS items P1, G9, P3, P2,G5, N1, N4, and N6.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	87	31
Number [Percentage of patients]	52.9	38.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1756
	Comments
	Method	Chi-squared
	Comments

5. Secondary Outcome

Title	Mean Change From Baseline in the PANSS Total Score
Description	The PANSS consists of 3 subscales (Positive Subscale, 7 constructs, scores ranged from 7-49, Negative Subscale, 7 constructs, scores ranged from 7-49, General Psychopathology Subscale, 16 constructs, scores ranged from 16-112) containing a total of 30 symptom constructs. For each symptom construct, severity was 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. The PANSS total score ranged from 30-210 with a higher score indicating more severe symptoms. A negative change score indicates improvement.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients who had PANSS total scores at both baseline and at least 1 post-baseline time point in Phase 4. Last observation carried forward was implemented to impute the missing data at post-baseline visits. Baseline was not carried forward in imputing the missing data at post-baseline visits.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	25	4
Least Squares Mean (Standard Error) [Units on a scale]	1.43 (0.756)	11.55 (1.066)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA included treatment as a term and baseline as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.11
	Confidence Interval	(2-Sided) 95%; -12.68 to -7.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Mean Change From Baseline in the Clinical Global Impression - Severity (CGI-S) Score
Description	The severity of illness for each patient was rated using the CGI-S. 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 CGI-S score ranged from 0-7 with a higher score indicating greater illness. A negative change score indicates improvement.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients who had CGI-S scores at both baseline and at least 1 post-baseline time point in Phase 4. Last observation carried forward was implemented to impute the missing data at post-baseline visits. Baseline was not carried forward in imputing the missing data at post-baseline visits.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	266	134
Mean (Standard Error) [Units on a scale]	0.14 (0.051)	0.66 (0.073)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA included treatment as a term and baseline as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -0.70 to -0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline in the PANSS Positive Subscale Score
Description	The PANSS Positive Subscale consists of 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). For each symptom construct, severity was 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. Scores on each subscale ranged from 7-49 with a higher score indicating more severe symptoms. A negative change score indicates improvement.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients who had PANSS sub-scale scores at both baseline and at least 1 post-baseline time point in Phase 4. Last observation carried forward was implemented to impute the missing data at post-baseline visits. Baseline was not carried forward in imputing the missing data at post-baseline visits.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	266	134
Least Squares Mean (Standard Error) [Units on a scale]	0.44 (0.265)	4.25 (0.374)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments	Positive Subscale Score
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA included treatment as a term and baseline as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.82
	Confidence Interval	(2-Sided) 95%; -4.72 to -2.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Mean Change From Baseline in the PANSS Negative Subscale Score
Description	The PANSS Negative Subscale consists of 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive pathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking). For each symptom construct, severity was 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. Scores on each subscale ranged from 7-49 with a higher score indicating more severe symptoms. A negative change score indicates improvement.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients who had PANSS sub-scale scores at both baseline and at least 1 post-baseline time point in Phase 4. Last observation carried forward was implemented to impute the missing data at post-baseline visits. Baseline was not carried forward in imputing the missing data at post-baseline visits.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	266	134
Least Squares Mean (Standard Error) [Units on a scale]	0.19 (0.201)	1.55 (0.284)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments	The ANCOVA included treatment as a term and baseline as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.36
	Confidence Interval	(2-Sided) 95%; -2.04 to -0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Mean Clinical Global Impression-Improvement (CGI-I) Score
Description	The efficacy of the study medication was rated for each patient using the CGI-I scale. The rater or investigator rated the patient's total improvement whether or not it was due entirely to drug treatment. All responses were compared to the patient's condition at Baseline. Response choices included: 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. The CGI-I score ranged from 0-7 with a higher score indicating less improvement/worsening.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients who had CGI-I scores at both baseline and at least 1 post-baseline time point in Phase 4. Last observation carried forward was implemented to impute the missing data at post-baseline visits. Baseline was not carried forward in imputing the missing data at post-baseline visits.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	266	133
Mean (Standard Deviation) [Units on a scale]	3.70 (1.05)	4.53 (1.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

10. Secondary Outcome

Title	Time to Discontinuation
Description	Time to discontinuation was defined as the date of randomization to the date of study discontinuation.
Time Frame	Baseline of the depot maintenance phase to the end of the study (Week 52)

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: All randomized patients.

Arm/Group Title	Aripiprazole Depot	Placebo Depot
Arm/Group Description	Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.	Patients received placebo intramuscularly every 28 days for 52 weeks.
Measure Participants	269	134
Median (95% Confidence Interval) [Days]	NA	162

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Depot, Placebo Depot
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments

Adverse Events

Time Frame	Adverse events were reported from the time of the signing of informed consent until the end of the study (up to 106 weeks).
Adverse Event Reporting Description	Safety population: All subjects who received at least 1 dose of study medication.
Arm/Group Title	Conversion Phase		Oral Stabilization Phase		Depot Stabilization Phase		Aripiprazole Depot - Depot Maintenance Phase		Placebo Depot - Depot Maintenance Phase
Arm/Group Description	During the Conversion Phase, patients were cross-titrated from other antipsychotics to oral non-generic aripiprazole monotherapy.		During the Oral Stabilization Phase, patients were stabilized on an oral dose of aripiprazole ranging from 10 mg to 30 mg daily.		During the IM Depot Stabilization Phase, patients were stabilized on aripiprazole IM depot.		Patients received aripiprazole 300 mg or 400 mg depot intramuscularly every 28 days for 52 weeks.		Patients received placebo intramuscularly every 28 days for 52 weeks.
All Cause Mortality
	Conversion Phase		Oral Stabilization Phase		Depot Stabilization Phase		Aripiprazole Depot - Depot Maintenance Phase		Placebo Depot - Depot Maintenance Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Conversion Phase		Oral Stabilization Phase		Depot Stabilization Phase		Aripiprazole Depot - Depot Maintenance Phase		Placebo Depot - Depot Maintenance Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/632 (2.1%)		10/709 (1.4%)		25/576 (4.3%)		11/269 (4.1%)		9/134 (6.7%)
Blood and lymphatic system disorders
Anaemia	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Cardiac disorders
Acute myocardial infarction	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Cardiac failure congestive	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Coronary artery insufficiency	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Myocardial ischaemia	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Sinus bradycardia	0/632 (0%)		0/709 (0%)		0/576 (0%)		0/269 (0%)		1/134 (0.7%)
Gastrointestinal disorders
Diarrhoea	0/632 (0%)		0/709 (0%)		0/576 (0%)		0/269 (0%)		1/134 (0.7%)
General disorders
Chest pain	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Hepatobiliary disorders
Biliary colic	0/632 (0%)		0/709 (0%)		0/576 (0%)		0/269 (0%)		1/134 (0.7%)
Infections and infestations
Cholecystitis infective	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Gastroenteritis	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Lobar pneumonia	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Injury, poisoning and procedural complications
Rib fracture	1/632 (0.2%)		0/709 (0%)		0/576 (0%)		0/269 (0%)		0/134 (0%)
Wrist fracture	1/632 (0.2%)		1/709 (0.1%)		0/576 (0%)		0/269 (0%)		0/134 (0%)
Femur fracture	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Gun shot wound	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Injury	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Multiple injuries	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Investigations
Blood creatine phosphokinase increased	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Hyperglycaemia	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Pancreatic carcinoma	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Nervous system disorders
Convulsion	1/632 (0.2%)		0/709 (0%)		0/576 (0%)		0/269 (0%)		0/134 (0%)
Syncope	1/632 (0.2%)		0/709 (0%)		0/576 (0%)		0/269 (0%)		0/134 (0%)
Paraesthesia	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Grand mal convulsion	0/632 (0%)		0/709 (0%)		0/576 (0%)		0/269 (0%)		1/134 (0.7%)
Psychiatric disorders
Psychotic disorder	2/632 (0.3%)		1/709 (0.1%)		2/576 (0.3%)		4/269 (1.5%)		4/134 (3%)
Schizophrenia	6/632 (0.9%)		6/709 (0.8%)		9/576 (1.6%)		2/269 (0.7%)		2/134 (1.5%)
Schizophrenia, paranoid type	2/632 (0.3%)		1/709 (0.1%)		2/576 (0.3%)		0/269 (0%)		0/134 (0%)
Suicidal ideation	2/632 (0.3%)		0/709 (0%)		0/576 (0%)		2/269 (0.7%)		0/134 (0%)
Delusion	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Hallucination	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Paranoia	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Psychiatric symptom	0/632 (0%)		1/709 (0.1%)		0/576 (0%)		0/269 (0%)		0/134 (0%)
Schizoaffective disorder	0/632 (0%)		0/709 (0%)		1/576 (0.2%)		0/269 (0%)		0/134 (0%)
Hallucination, auditory	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Suicide attempt	0/632 (0%)		0/709 (0%)		0/576 (0%)		1/269 (0.4%)		0/134 (0%)
Other (Not Including Serious) Adverse Events
	Conversion Phase		Oral Stabilization Phase		Depot Stabilization Phase		Aripiprazole Depot - Depot Maintenance Phase		Placebo Depot - Depot Maintenance Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	113/632 (17.9%)		50/709 (7.1%)		184/576 (31.9%)		103/269 (38.3%)		43/134 (32.1%)
General disorders
Injection site pain	0/632 (0%)		2/709 (0.3%)		34/576 (5.9%)		8/269 (3%)		5/134 (3.7%)
Infections and infestations
Nasopharyngitis	14/632 (2.2%)		6/709 (0.8%)		11/576 (1.9%)		10/269 (3.7%)		7/134 (5.2%)
Investigations
Weight increased	8/632 (1.3%)		16/709 (2.3%)		40/576 (6.9%)		26/269 (9.7%)		13/134 (9.7%)
Nervous system disorders
Headache	45/632 (7.1%)		23/709 (3.2%)		34/576 (5.9%)		16/269 (5.9%)		7/134 (5.2%)
Akathisia	30/632 (4.7%)		33/709 (4.7%)		36/576 (6.3%)		15/269 (5.6%)		8/134 (6%)
Tremor	16/632 (2.5%)		14/709 (2%)		21/576 (3.6%)		16/269 (5.9%)		2/134 (1.5%)
Psychiatric disorders
Insomnia	76/632 (12%)		50/709 (7.1%)		46/576 (8%)		27/269 (10%)		12/134 (9%)
Anxiety	27/632 (4.3%)		29/709 (4.1%)		38/576 (6.6%)		16/269 (5.9%)		10/134 (7.5%)

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.