An Efficacy and Safety Study of Extended-Release (ER) Paliperidone in Adolescent Participants With Schizophrenia

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01009047
• Collaborator: (none)
• Enrollment: 228
• Locations: 44
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of extended-release (ER) paliperidone compared to aripiprazole (atypical antipsychotic) in symptomatic (having symptoms) adolescent participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations [imagining things], and withdrawal into the self) .

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Paliperidone extended release (ER); Drug: Aripiprazole	Phase 3

Detailed Description

This is a multi-center (conducted in more than 1 center), double-blind (neither physician nor participant knows the name of the assigned drug), randomized (study drug is assigned by chance), active-controlled (paliperidone ER is compared to aripiprazole), parallel-group (a medical research study comparing the response in 2 or more groups of participants receiving different treatments), flexible-dose (the physician has the freedom to give different doses to the participant depending on how they respond to treatment) study designed to determine the efficacy and safety of paliperidone ER in symptomatic adolescents (12 to 17 years of age) with schizophrenia. The total duration of the study will be approximately 29 weeks. The study consists of 3 phases: a Screening phase up to 3 weeks (with a possible overlapping washout period), a Double-blind acute phase of 8 weeks, and a Double-blind maintenance phase of 18 weeks. Participants will be randomly assigned to 1 of the 2 treatment groups (paliperidone ER or aripiprazole flexible oral doses). Dosage will be adjusted at the scheduled visits. Efficacy of the participants will primarily be evaluated through Positive and Negative Syndromes Scale (PANSS). Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 228 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Double-Blind, Active-Controlled, Flexible-Dose, Parallel-Group Study of the Efficacy and Safety of Extended Release Paliperidone for the Treatment of Symptoms of Schizophrenia in Adolescent Subjects, 12 to 17 Years of Age
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paliperidone extended-release (ER) Paliperidone ER will be administered as oral capsule at a dose of 6 milligram (mg) for 1 week and then will be administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Drug: Paliperidone extended release (ER); Paliperidone ER will be administered as oral capsule at a dose of 6 mg for 1 week and then will be administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.
Active Comparator: Aripiprazole Aripiprazole will be administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4, 10 mg Days 5, 6 and 7; and then will be administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.	Drug: Aripiprazole; Aripiprazole will be administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4, 10 mg Days 5, 6 and 7; and then will be administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56 [Baseline and Day 56]

   The PANSS is a 30-item scale with each item rated on a scale of 1 (absent) to 7 (extreme psychopathology), designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.

Secondary Outcome Measures

1. Change From Baseline in PANSS Total Score at Day 182 [Baseline and Day 182]

   The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.

2. Change From Baseline in Marder Factor Negative Symptoms Score at Day 56 and 182 [Baseline, Day 56 and Day 182]

   The PANSS negative subscale based on marder factor assesses 7 negative-symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology).

3. Change From Baseline in Other Marder Factors Scores at Day 56 and 182 [Baseline, Day 56 and 182]

   The subscales based on marder factors are: positive symptoms, disorganised thoughts factor, uncontrolled hostility/excitement factor, and anxiety/depression factor. The symptoms are rated on a 7-point scale, with a range of 8 to 56 for positive symptoms, 7 to 49 for disorganized thoughts and 4 to 28 for Uncontrolled hostility/excitement and anxiety/depression. Higher score indicate worsening.

4. Change From Baseline in Other PANSS Factors and Subscales at Day 56 and 182 [Baseline, Day 56 and 182]

   The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a scale of 1 (absent) to 7 (extreme).

5. Number of Participants With Clinical Stability [Day 56 and 182]

   Clinical stability is defined as a decrease of 20 percent or more from Baseline in PANSS total score and CGI-S score less than or equal to 4 at Days 56 and 182, no hospitalizations due to psychiatric illness and no emergence of clinically significant suicidal or homicidal ideation during the maintenance phase.

6. Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Days 56 and 182 [Baseline, Day 56 and 182]

   The CGI-S rating scale is a 7-point global assessment that measures the Clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.

7. Change From Baseline in Personal and Social Performance (PSP) Scores at Day 56 and 182 [Baseline, Day 56 and Day 182]

   The PSP scale assesses degree of a participants' dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The results of the assessment are converted to a numerical score to rate degree of difficulty (1=absent to 6=very severe) in each of the 4 domains. Based on 4 domains there will be 1 total score (total score ranges from 1 to 100, divided into 10 equal intervals). Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.

8. Number of Participants With PANSS Response [Day 56 and 182]

   The PANSS is a 30-item scale with each item rated on a scale of 1 (absent) to 7 (extreme psychopathology), designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Participants with PANSS response were defined as those who achieved greater than or equal to 20 percent or higher reduction from Baseline in the PANSS total score at Day 56 and 182.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must currently meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for schizophrenia and have experienced symptoms of the illness for at least 1 year, and they should have had at least treatment with 1 antipsychotic before participation in this study

• Participants having a Positive and Negative Syndromes Scale (PANSS) score between 60 and 120 inclusive at Screening

• Female participants must be incapable of pregnancy, or if heterosexually active and capable of pregnancy, have been using an acceptable method of contraception for at least 1 month before study entry and agree to continue use contraception methods for the duration of the study, or if sexually abstinent (not having sexual intercourse) and capable of pregnancy, must agree to continue abstinence or to use an acceptable method of birth control

• Participants must not be a danger to themselves or others, and must have family support available to be maintained as out-patients

• Participants with a weight of equal to or greater than 29 kilogram

Exclusion Criteria:

• Participants with mild (not serious), moderate (medium level of seriousness), or severe (very serious, life threatening) mental retardation

• Participants with a known or suspected history of substance dependence (including alcohol, but excluding nicotine or caffeine) as per the DSM-IV criteria in the 3 months before Screening

• Participants with a history of certain neurological (pertaining to the nervous system) disorders or insulin-dependent diabetes mellitus (disorder in which there is decreased insulin in the body or the body's insulin is not effective, resulting in high blood sugar, increased thirst and urine, and many other side effects)

• Participants who have received a depot injectable antipsychotic within 2 treatment cycles before the Screening visit

• Participants who have received clozapine in 2 months before the Baseline visit (Day 1 of Week 1)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Dothan	Alabama	United States
2		Santa Ana	California	United States
3		Atlanta	Georgia	United States
4		Smyrna	Georgia	United States
5		Lake Charles	Louisiana	United States
6		Shreveport	Louisiana	United States
7		Jaipur		India
8		Kanpur Uttarpradeh		India
9		Lucknow Gpo		India
10		Mangalore		India
11		Varanasi		India
12		Bucharest		Romania
13		Chelyabinsk		Russian Federation
14		Ekaterinburg Na		Russian Federation
15		Krasnodar N/A		Russian Federation
16		Moscow N/A		Russian Federation
17		Moscow Russia		Russian Federation
18		Nizhniy Novgorod		Russian Federation
19		Novosibirsk		Russian Federation
20		Saint Petersburg		Russian Federation
21		Samara		Russian Federation
22		Saratov		Russian Federation
23		Smolensk Region N/A		Russian Federation
24		St Petersburg		Russian Federation
25		St-Petersburg		Russian Federation
26		Tomsk Na		Russian Federation
27		Yaroslavl N/A		Russian Federation
28		Bratislava		Slovakia
29		Badajoz		Spain
30		Esplugues De Llobregat		Spain
31		Madrid		Spain
32		Paterna		Spain
33		Sabadell		Spain
34		Sevilla		Spain
35		Valladolid		Spain
36		Donetsk		Ukraine
37		Glevakha		Ukraine
38		Ivano-Frankivsk		Ukraine
39		Ivano-Frankovsk		Ukraine
40		Kharkiv		Ukraine
41		Kherson		Ukraine
42		Kiev		Ukraine
43		Poltava		Ukraine
44		Simferopol		Ukraine

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01009047
• Other Study ID Numbers: CR016675; R076477PSZ3003
• First Posted: Nov 6, 2009
• Last Update Posted: Jun 21, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Janssen Research & Development, LLC: Schizophrenia; Paliperidone; Aripiprazole
• Additional relevant MeSH terms: Schizophrenia; Aripiprazole; Paliperidone Palmitate

Study Results

Participant Flow

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 milligram (mg) for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Period Title: Overall Study
STARTED	113	115
COMPLETED	85	89
NOT COMPLETED	28	26

Baseline Characteristics

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole	Total
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.	Total of all reporting groups
Overall Participants	112	114	226
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	15.3 (1.46)	15.4 (1.45)	15.3 (1.46)
Sex: Female, Male (Count of Participants)
Female	39 34.8%	38 33.3%	77 34.1%
Male	73 65.2%	76 66.7%	149 65.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56
Description	The PANSS is a 30-item scale with each item rated on a scale of 1 (absent) to 7 (extreme psychopathology), designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.
Time Frame	Baseline and Day 56

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Baseline	89.6 (12.22)	92.0 (12.09)
Change at Day 56	-19.3 (13.80)	-19.8 (14.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.935
	Comments	Analysis of covariance (ANCOVA) model with treatment (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least-squares (LS) mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -3.46 to 3.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.83
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in PANSS Total Score at Day 182
Description	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.
Time Frame	Baseline and Day 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Baseline	89.6 (12.22)	92.0 (12.09)
Change at Day 182	-25.6 (16.88)	-26.8 (18.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.877
	Comments	Analysis of covariance (ANCOVA) model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -4.68 to 4.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.20
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Marder Factor Negative Symptoms Score at Day 56 and 182
Description	The PANSS negative subscale based on marder factor assesses 7 negative-symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology).
Time Frame	Baseline, Day 56 and Day 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Baseline	23.2 (4.92)	23.3 (4.54)
Change at Day 56	-4.3 (4.56)	-4.7 (4.61)
Change at Day 182	-6.0 (5.51)	-6.2 (5.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.341
	Comments	Day 56: Analysis of covariance (ANCOVA) model with treatment (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -0.55 to 1.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.54
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.723
	Comments	Day 182: Analysis of covariance (ANCOVA) model with treatment (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -1.06 to 1.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.66
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Other Marder Factors Scores at Day 56 and 182
Description	The subscales based on marder factors are: positive symptoms, disorganised thoughts factor, uncontrolled hostility/excitement factor, and anxiety/depression factor. The symptoms are rated on a 7-point scale, with a range of 8 to 56 for positive symptoms, 7 to 49 for disorganized thoughts and 4 to 28 for Uncontrolled hostility/excitement and anxiety/depression. Higher score indicate worsening.
Time Frame	Baseline, Day 56 and 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Baseline: Positive symptoms	24.6 (4.08)	24.9 (4.32)
Change at Day 56: Positive symptoms	-6.1 (4.96)	-5.6 (4.83)
Change at Day 182: Positive symptoms	-7.8 (5.82)	-7.8 (6.03)
Baseline: Negative symptoms	23.2 (4.92)	23.3 (4.54)
Change at Day 56: Negative symptoms	-4.3 (4.56)	-4.7 (4.61)
Change at Day 182: Negative symptoms	-6.0 (5.51)	-6.2 (5.84)
Baseline: Disorganized thoughts	21.4 (4.40)	22.1 (3.86)
Change at Day 56: Disorganized thoughts	-4.0 (3.34)	-4.1 (3.40)
Change at Day 182: Disorganized thoughts	-5.5 (4.18)	-5.7 (4.46)
Baseline: Uncontrolled hostility	10.7 (3.19)	11.7 (3.48)
Change at Day 56: Uncontrolled hostility	-2.5 (2.67)	-2.9 (3.05)
Change at Day 182: Uncontrolled hostility	-3.2 (3.11)	-3.8 (3.97)
Baseline: Anxiety/depression	9.7 (3.17)	10.0 (3.26)
Change at Day 56: Anxiety/depression	-2.4 (3.08)	-2.6 (2.81)
Change at Day 182: Anxiety/depression	-3.0 (3.29)	-3.2 (3.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.351
	Comments	Change at Day 56: Positive Symptoms - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.691
	Comments	Change at Day 182:Positive Symptoms - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.965
	Comments	Change at Day 56: Disorganized thoughts - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.766
	Comments	Change at Day 182: Disorganized thoughts - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.984
	Comments	Change at Day 56: Uncontrolled hostility/ excitement - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.985
	Comments	Change at Day 182: Uncontrolled Hositility/ Excitement - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.803
	Comments	Change at Day 56: Anxiety/ depression - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate.
	Method	ANCOVA
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.745
	Comments	Change at Day 182: Anxiety/ depression - ANCOVA model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate.
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Change From Baseline in Other PANSS Factors and Subscales at Day 56 and 182
Description	The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a scale of 1 (absent) to 7 (extreme).
Time Frame	Baseline, Day 56 and 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Baseline: Positive Subscale	21.5 (4.14)	22.5 (4.26)
Change at Day 56: Positive Subscale	-6.4 (4.54)	-6.2 (4.91)
Change at Day 182: Positive Subscale	-8.0 (5.16)	-8.3 (6.09)
Baseline: Negative Subscale	23.8 (4.55)	24.2 (4.32)
Change at Day 56: Negative Subscale	-4.2 (4.25)	4.5 (4.25)
Change at Day 182: Negative Subscale	-5.7 (5.15)	-6.1 (5.47)
Baseline: General Psychopathology	44.3 (7.47)	45.3 (7.01)
Change at Day 56: General Psychopathology	-8.7 (7.35)	-9.1 (7.25)
Change at Day 182: General Psychopathology	-11.9 (9.02)	-12.4 (9.41)

6. Secondary Outcome

Title	Number of Participants With Clinical Stability
Description	Clinical stability is defined as a decrease of 20 percent or more from Baseline in PANSS total score and CGI-S score less than or equal to 4 at Days 56 and 182, no hospitalizations due to psychiatric illness and no emergence of clinically significant suicidal or homicidal ideation during the maintenance phase.
Time Frame	Day 56 and 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Number [Participants]	58 51.8%	68 59.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.296
	Comments	Generalized Cochran- Mantel- Haenszel test for row mean score differences controlling for country was used.
	Method	Cochran-Mantel-Haenszel
	Comments

7. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score at Days 56 and 182
Description	The CGI-S rating scale is a 7-point global assessment that measures the Clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.
Time Frame	Baseline, Day 56 and 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Baseline	4.0	4.0
Change at Day 56	-1.0	-1
Change at Day 182	-1.0	-1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.843
	Comments	Change at Day 56: ANCOVA model on ranks with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value (unranked) as a covariate was used.
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.914
	Comments	Change at Day 182: ANCOVA model on ranks with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value (unranked) as a covariate was used.
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Change From Baseline in Personal and Social Performance (PSP) Scores at Day 56 and 182
Description	The PSP scale assesses degree of a participants' dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The results of the assessment are converted to a numerical score to rate degree of difficulty (1=absent to 6=very severe) in each of the 4 domains. Based on 4 domains there will be 1 total score (total score ranges from 1 to 100, divided into 10 equal intervals). Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.
Time Frame	Baseline, Day 56 and Day 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Baseline	49.8 (10.32)	49.2 (10.21)
Change at Day 56	12.2 (11.72)	12.2 (10.17)
Change at Day 182	17.1 (14.46)	17.1 (14.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.895
	Comments	Change at Day 56: Analysis of covariance (ANCOVA) model with treatment groups(paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -2.34 to 2.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.705
	Comments	Change at Day 182: Analysis of covariance (ANCOVA) model with treatment groups (paliperidone ER, aripiprazole) and country as factors, and baseline value as a covariate was used.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -2.64 to 3.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.66
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants With PANSS Response
Description	The PANSS is a 30-item scale with each item rated on a scale of 1 (absent) to 7 (extreme psychopathology), designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Participants with PANSS response were defined as those who achieved greater than or equal to 20 percent or higher reduction from Baseline in the PANSS total score at Day 56 and 182.
Time Frame	Day 56 and 182

Outcome Measure Data

Analysis Population Description

The ITT population included all randomly assigned participants who received at least 1 dose of double-blind study drug, had both a Baseline measurement and at least 1 Post-Baseline measurement in the double-blind phase. Last observation carried forward (LOCF) method was used.

Arm/Group Title	Paliperidone Extended Release (ER)	Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.	Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
Measure Participants	112	114
Day 56	76 67.9%	87 76.3%
Day 182	86 76.8%	93 81.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.119
	Comments	Day 56: Generalized Cochran-Mantel-Haenszel test for row mean score differences was used.
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Extended Release (ER), Aripiprazole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.444
	Comments	Day 182: Generalized Cochran-Mantel-Haenszel test for row mean score differences was used.
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	Baseline up to Week 26
Adverse Event Reporting Description	The safety population included all randomly assigned participants who received at least 1 dose of double-blind study drug. A total of 113 participants in the paliperidone ER group and 114 participants in the aripiprazole group received at least 1 dose of double-blind study medication and were included in the safety analysis set.
Arm/Group Title	Paliperidone Extended Release (ER)		Aripiprazole
Arm/Group Description	Paliperidone ER administered as oral capsule at a dose of 6 mg for 1 week and then administered at a dose of either 3, 6 or 9 mg up to Week 26, once daily in the morning.		Aripiprazole administered as oral capsule at a dose of 2 mg on Days 1 and 2, 5 mg on Days 3 and 4; 10 mg on Days 5, 6 and 7; and then administered as a dose of either 5 or 10 or 15 mg up to Week 26, once daily in the morning.
All Cause Mortality
	Paliperidone Extended Release (ER)		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Paliperidone Extended Release (ER)		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/113 (6.2%)		7/114 (6.1%)
Infections and infestations
Sinusitis	1/113 (0.9%)		0/114 (0%)
Upper respiratory infection	0/113 (0%)		1/114 (0.9%)
Psychiatric disorders
Agitation	1/113 (0.9%)		1/114 (0.9%)
Anxiety	1/113 (0.9%)		0/114 (0%)
Schizophrenia	1/113 (0.9%)		4/114 (3.5%)
Schizophrenia, paranoid type	1/113 (0.9%)		0/114 (0%)
Suicide attempt	1/113 (0.9%)		0/114 (0%)
Psychotic disorder	1/113 (0.9%)		1/114 (0.9%)
Other (Not Including Serious) Adverse Events
	Paliperidone Extended Release (ER)		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/113 (55.8%)		50/114 (43.9%)
Gastrointestinal disorders
Vomiting	8/113 (7.1%)		1/114 (0.9%)
Nausea	4/113 (3.5%)		7/114 (6.1%)
General disorders
Asthenia	6/113 (5.3%)		1/114 (0.9%)
Investigations
Weight increased	12/113 (10.6%)		7/114 (6.1%)
Metabolism and nutrition disorders
Decreased appetite	2/113 (1.8%)		6/114 (5.3%)
Musculoskeletal and connective tissue disorders
Muscle rigidity	7/113 (6.2%)		3/114 (2.6%)
Nervous system disorders
Headache	12/113 (10.6%)		5/114 (4.4%)
Akathisia	13/113 (11.5%)		9/114 (7.9%)
Somnolence	12/113 (10.6%)		12/114 (10.5%)
Tremor	12/113 (10.6%)		11/114 (9.6%)
Sedation	6/113 (5.3%)		3/114 (2.6%)
Psychiatric disorders
Insomnia	6/113 (5.3%)		9/114 (7.9%)
Schizophrenia	3/113 (2.7%)		10/114 (8.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If an Investigator wishes to publish information from the study, a copy of the manuscript must be provided to the Sponsor for review at least 60 days before submission for publication. If requested by the Sponsor, the Investigator will withhold it up to an additional 60 days to allow for filing of a patent application. The Sponsor will not change or suppress the scientific content. For multi-center study, results may not be published before the primary endpoints of a study have been published.