An Efficacy and Safety Study of One Dosage of Paliperidone Extended Release (ER) in Treating Patients With Schizophrenia

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00524043
• Collaborator: (none)
• Enrollment: 201
• Locations: 20
• Arms: 3
• Duration (Months): 14
• Patients Per Site: 10.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of 1.5 mg/day dose of paliperidone Extended Release (ER) as compared with placebo when used to treat patients with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Paliperidone ER; Drug: Placebo; Drug: Paliperidone ER	Phase 4

Detailed Description

Currently, treatment of acute symptoms in schizophrenia is less than ideal, up to one-third of patients with schizophrenia do not respond to current treatments, and poor drug tolerability can decrease a patient's ability to remain on treatment. Paliperidone ER doses in the range of 3 mg/day to 12 mg/day have been approved for the treatment of patients with schizophrenia. A lower dosage form of paliperidone ER be efficacious and may reduce the risk of certain adverse effects. This study will evaluate the efficacy of 1 fixed (ie, it does not change during the study) dosage of paliperidone ER (1.5 mg/day) compared with placebo. One fixed dosage of paliperidone ER (6.0 mg/day) will be given to some patients as an active (it has already been shown to have efficacy) control. This is a multicenter, double-blind (neither the patient nor the study-site personnel know which treatment the patient is receiving), randomized (patients are assigned to a treatment group by chance), placebo-controlled (some patients will receive placebo and no active drug), parallel-group (patients in all groups follow the same study design) study in adults who were diagnosed with schizophrenia at least 1 year before screening and who are experiencing an acute episode. The study starts with an up-to-5-day screening phase to find out if the patient is eligible for the study. The screening phase includes a 3- to 5-day washout (the medication dosage is tapered down and finally stopped) of any medications that are being taken by a patient but that are not allowed during the study. A 6-week double-blind treatment phase follows and finishes with an end-of-study visit. A post-study visit to collect additional safety data will be scheduled for 1 week after a patient receives his or her last dose of study drug. The length of the entire study is about 8 weeks. Patients who withdraw from the study before completing the double-blind treatment phase will complete the end-of-study visit procedures at the time they withdraw and the post-study visit 1 week after receiving their last dose of study drug. For all patients leaving the study, the investigator will make every effort to see that they receive adequate continuity of care. At baseline (the visit just before a patient takes the first dose of study drug), all patients will be randomly assigned to 1 of the 3 possible treatment groups to receive paliperidone ER 1.5 mg/day, paliperidone ER 6 mg/day, or placebo once daily for 6 weeks. Patients must be voluntary inpatients at the time of randomization, and they must remain in the hospital for a minimum of 8 days. Efficacy will be measured using the following rating scales: the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S), the Personal and Social Performance Scale (PSP), and the Medical Outcomes Study Short Form Health Survey-36 (MOS SF-36). Safety will be evaluated using physical examinations, ECGs, clinical laboratory testing (hematology, serum chemistry, and urinalysis), testings for pregnancy, and monitoring for adverse events including extrapyramidal symptoms (EPS) using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Rating Scale (SAS). The study hypothesis is that Paliperidone ER at 1.5 mg per day will be effective in the treatment of schizophrenia as measured by the change in total PANSS score between baseline and endpoint in comparison with placebo. Oral paliperidone ER 1.5 mg or 6.0 mg tablets or matching oral placebo tablets taken once daily in the morning for 6 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 201 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Fixed Dosage of 1.5 mg/Day of Paliperidone Extended Release (ER) in the Treatment of Subjects With Schizophrenia
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 Paliperidone ER 1.5 mg tablet once daily for 6 weeks	Drug: Paliperidone ER; 1.5 mg tablet once daily for 6 weeks
Active Comparator: 002 Paliperidone ER 6 mg tablet once daily for 6 weeks	Drug: Paliperidone ER; 6 mg tablet once daily for 6 weeks
Placebo Comparator: 003 Placebo Once daily for 6 weeks	Drug: Placebo; Once daily for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in PANSS Total Score at the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment). [Baseline, 6 weeks]

   The Positive and Negative Syndrome Scale (PANSS) is a tool used by psychiatrists to measure the symptoms of psychosis experienced by a patient with schizophrenia. It includes 30 items that produce a total score ranging from a minimum of 30 (indicating least severe symptoms of illness) to a maximum of 120 (indicating most severe symptoms of illness). A negative change in score from baseline to end point indicates improvement in the symptoms of illness.

Secondary Outcome Measures

1. Change From Baseline to the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment) in CGI-S [Baseline, 6 weeks]

   The Clinical Global Impression-Severity (CGI-S) rating scale is used by psychiatrists to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). The scale permits a global evaluation of the patient's condition at a given time.

2. Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in PSP Score [Baseline, 6 weeks]

   The Personal and Social Performance (PSP) scale assesses the degree of difficulty (ranging from i [absent] to vi [very severe]) a patient exhibits over a 1-month period in socially useful activities, personal and social relationships, self care, and disturbing and aggressive behavior. The overall score ranges from 1 to 100. Patients with scores of 71 to 100 have a mild degree of difficulty; patients with scores from 31 to 70 have various degrees of disability; and patients with scores of 30 or less function so poorly as to require intensive supervision.

3. Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Physical Component Summary Scale Score [Baseline, 6 weeks]

   The Medical Outcomes Study Short Form Health Survey-36 (MOS SF-36) is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 subscale scores: the Physical Component Summary and the Mental Component Summary.

4. Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Mental Component Summary Scale Score [Baseline, 6 weeks]

   The MOS SF-36 is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (295.10, 295.20, 295.30, 295.60, 295.90) at least 1 year before screening

• Experiencing an acute episode with a total PANSS score at screening of between 70 and 120

• Are otherwise physically healthy

• Agree to at least 8 days of voluntary hospitalization.

Exclusion Criteria:

• Active comorbid DSM-IV axis I diagnosis other than schizophrenia (nicotine and caffeine dependence are not exclusionary)

• Treatment with antidepressants (unless a subject has been on a stable dosage for at least 3 months before baseline) other than monoamine oxidase inhibitors

• DSM-IV diagnosis of substance dependence within 6 months before screening evaluation (nicotine and caffeine dependence are not exclusionary)

• Any medical condition that could potentially alter the absorption, metabolism, or excretion of the study medication, such as Crohn's disease, liver disease, or renal disease

• Relevant history of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Cerritos	California	United States
2		Torrance	California	United States
3		Washington	District of Columbia	United States
4		Bradenton	Florida	United States
5		Leesburg	Florida	United States
6		Atlanta	Georgia	United States
7		Rockville	Maryland	United States
8		Nutley	New Jersey	United States
9		Cedarhurst	New York	United States
10		Hollis	New York	United States
11		Moore	Oklahoma	United States
12		Austin	Texas	United States
13		Calicut		India
14		Hyderabad		India
15		Mumbai		India
16		Pune		India
17		Varanasi		India
18		Hualien		Taiwan
19		Tainan		Taiwan
20		Taipei		Taiwan

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Study of the Efficacy and Safety of One Dosage of Paliperidone Extended Release (ER) in Treating Patients With Schizophrenia

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00524043
• Other Study ID Numbers: CR013771; R076477SCH4012
• First Posted: Sep 3, 2007
• Last Update Posted: Jun 4, 2014
• Last Verified: May 1, 2014

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Schizophrenia
• Additional relevant MeSH terms: Schizophrenia; Paliperidone Palmitate

Study Results

Participant Flow

Recruitment Details	The study began on 21 September 2007 when the first patient was enrolled and ended on 20 November 2008 when the last patient left the study. The study was performed at medical clinics in the United States, India, and Taiwan.
Pre-assignment Detail	Patients who wished to enter the study were screened and, if necessary, had prohibited medications (such as other antipsychotic drugs) washed out for 3 to 5 days before beginning the study. Eligible patients were excluded prior to beginning the study if, for example, they took a prohibited medication.

Arm/Group Title	Placebo	Paliperidone ER 6 mg	Paliperidone ER 1.5 mg
Arm/Group Description	One oral placebo tablet daily for 6 weeks.	Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.	Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.
Period Title: Overall Study
STARTED	64	70	66
COMPLETED	34	42	35
NOT COMPLETED	30	28	31

Baseline Characteristics

Arm/Group Title	Placebo	Paliperidone ER 6 mg	Paliperidone ER 1.5 mg	Total
Arm/Group Description	One oral placebo tablet daily for 6 weeks.	Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.	Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.	Total of all reporting groups
Overall Participants	64	70	66	200
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	64 100%	70 100%	66 100%	200 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.5 (11.57)	40.3 (12.84)	41.3 (10.96)	39.4 (11.95)
Sex: Female, Male (Count of Participants)
Female	18 28.1%	23 32.9%	16 24.2%	57 28.5%
Male	46 71.9%	47 67.1%	50 75.8%	143 71.5%
Region of Enrollment (participants) [Number]
India	23 35.9%	25 35.7%	24 36.4%	72 36%
Taiwan	7 10.9%	12 17.1%	9 13.6%	28 14%
United States	34 53.1%	33 47.1%	33 50%	100 50%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in PANSS Total Score at the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment).
Description	The Positive and Negative Syndrome Scale (PANSS) is a tool used by psychiatrists to measure the symptoms of psychosis experienced by a patient with schizophrenia. It includes 30 items that produce a total score ranging from a minimum of 30 (indicating least severe symptoms of illness) to a maximum of 120 (indicating most severe symptoms of illness). A negative change in score from baseline to end point indicates improvement in the symptoms of illness.
Time Frame	Baseline, 6 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set included all enrolled patients who received at least 1 dose of paliperidone ER or placebo and had both the baseline and at least 1 postbaseline efficacy assessment.

Arm/Group Title	Placebo	Paliperidone ER 6 mg	Paliperidone ER 1.5 mg
Arm/Group Description	One oral placebo tablet daily for 6 weeks.	Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.	Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.
Measure Participants	63	70	66
Mean (Standard Deviation) [units on a scale]	-11.7 (22.84)	-15.0 (26.02)	-8.9 (25.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paliperidone ER 1.5 mg
	Comments	Sample size estimation was based on the assumption that the difference between the paliperidone ER 1.5 mg dose group and the placebo group in the mean change in PANSS total score from baseline to end point was 11 points with a within-group standard deviation of 20 points. It was calculated that 65 patients were needed per treatment group to detect a statistically significant treatment difference between the paliperidone ER 1.5 mg dose group and the placebo group with a power of 87.5%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.504
	Comments	Based on ANCOVA model with treatment (Placebo, Paliperidone ER 1.5 mg, and Paliperidone ER 6 mg) and country as factors, and baseline value as a covariate. Comparison with placebo was without multiplicity adjustment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.8
	Confidence Interval	() 95%; -5.47 to 11.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.20
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paliperidone ER 6 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.431
	Comments	Based on ANCOVA model with treatment (Placebo, Paliperidone ER 1.5 mg, and Paliperidone ER 6 mg) and country as factors, and baseline value as a covariate. Comparison with placebo was without multiplicity adjustment.
	Method	ANCOVA
	Comments	Paliperidone ER 6 mg was used for assay sensitivity
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.3
	Confidence Interval	() 95%; -11.46 to 4.90
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.15
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment) in CGI-S
Description	The Clinical Global Impression-Severity (CGI-S) rating scale is used by psychiatrists to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). The scale permits a global evaluation of the patient's condition at a given time.
Time Frame	Baseline, 6 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set included all enrolled patients who received at least 1 dose of paliperidone ER or placebo and had both the baseline and at least 1 postbaseline efficacy assessment.

Arm/Group Title	Placebo	Paliperidone ER 6 mg	Paliperidone ER 1.5 mg
Arm/Group Description	One oral placebo tablet daily for 6 weeks.	Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.	Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.
Measure Participants	63	70	66
Median (Full Range) [units on a scale]	-1.0	-0.5	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paliperidone ER 1.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.626
	Comments	Based on ANCOVA model on ranks with treatment (Placebo, Paliperidone ER 1.5 mg, and Paliperidone ER 6 mg) and country as factors, and baseline value as a covariate. Comparison with placebo was without multiplicity adjustment.
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in PSP Score
Description	The Personal and Social Performance (PSP) scale assesses the degree of difficulty (ranging from i [absent] to vi [very severe]) a patient exhibits over a 1-month period in socially useful activities, personal and social relationships, self care, and disturbing and aggressive behavior. The overall score ranges from 1 to 100. Patients with scores of 71 to 100 have a mild degree of difficulty; patients with scores from 31 to 70 have various degrees of disability; and patients with scores of 30 or less function so poorly as to require intensive supervision.
Time Frame	Baseline, 6 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set included all enrolled patients who received at least 1 dose of paliperidone ER or placebo and had both the baseline and at least 1 postbaseline efficacy assessment.

Arm/Group Title	Placebo	Paliperidone ER 6 mg	Paliperidone ER 1.5 mg
Arm/Group Description	One oral placebo tablet daily for 6 weeks.	Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.	Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.
Measure Participants	63	70	66
Mean (Standard Deviation) [units on a scale]	1.6 (17.09)	5.7 (13.39)	2.9 (14.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paliperidone ER 1.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.870
	Comments	Based on ANCOVA model with treatment (placebo, paliperidone ER 1.5 mg, and paliperidone ER 6 mg) and country as factors, and baseline value as a covariate. Comparison with placebo was without multiplicity adjustment.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.4
	Confidence Interval	() 95%; -4.86 to 5.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.69
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Physical Component Summary Scale Score
Description	The Medical Outcomes Study Short Form Health Survey-36 (MOS SF-36) is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 subscale scores: the Physical Component Summary and the Mental Component Summary.
Time Frame	Baseline, 6 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set included all enrolled patients who received at least 1 dose of paliperidone ER or placebo and had both the baseline and at least 1 postbaseline efficacy assessment.

Arm/Group Title	Placebo	Paliperidone ER 6 mg	Paliperidone ER 1.5 mg
Arm/Group Description	One oral placebo tablet daily for 6 weeks.	Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.	Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.
Measure Participants	63	70	66
Mean (Standard Deviation) [units on a scale]	0.4 (6.94)	0.6 (9.45)	-0.2 (9.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paliperidone ER 1.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.126
	Comments	Based on ANCOVA model with treatment (placebo, paliperidone ER 1.5 mg, and paliperidone ER 6 mg) and country as factors and baseline value as a covariate. Comparison with placebo was without multiplicity adjustment.
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Mental Component Summary Scale Score
Description	The MOS SF-36 is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary.
Time Frame	Baseline, 6 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat analysis set included all enrolled patients who received at least 1 dose of paliperidone ER or placebo and had both the baseline and at least 1 postbaseline efficacy assessment.

Arm/Group Title	Placebo	Paliperidone ER 6 mg	Paliperidone ER 1.5 mg
Arm/Group Description	One oral placebo tablet daily for 6 weeks.	Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.	Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.
Measure Participants	63	70	66
Mean (Standard Deviation) [units on a scale]	3.5 (13.14)	6.1 (13.39)	2.1 (11.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Paliperidone ER 1.5 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.691
	Comments	Based on ANCOVA model with treatment (placebo, paliperidone ER 1.5 mg, and paliperidone ER 6 mg) and country as factors and baseline value as a covariate. Comparison with placebo was without multiplicity adjustment.
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Up to 8 weeks, including the screening period (2 to 6 days), the 6-week treatment period, and 1 week follow up. Monitoring for adverse events began after the patient was enrolled and continued until the last study-related procedure was performed.
Adverse Event Reporting Description	There were 65 patients randomly assigned to treatment with placebo, but 1 patient in the Placebo group did not receive any treatment. Thus any adverse events experienced by this subject are not reported here.
Arm/Group Title	Placebo		Paliperidone ER 6 mg		Paliperidone ER 1.5 mg
Arm/Group Description	One oral placebo tablet daily for 6 weeks.		Active comparator. One 6 mg oral tablet daily for 6 weeks. The 6 mg dose of paliperidone ER has been shown to have efficacy in previous studies.		Experimental dose of paliperidone ER. One 1.5 mg oral tablet daily for 6 weeks.
All Cause Mortality
	Placebo		Paliperidone ER 6 mg		Paliperidone ER 1.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Paliperidone ER 6 mg		Paliperidone ER 1.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/64 (10.9%)		5/70 (7.1%)		7/66 (10.6%)
Psychiatric disorders
Psychotic disorder	6/64 (9.4%)	6	2/70 (2.9%)	2	4/66 (6.1%)	4
Schizophrenia	0/64 (0%)	0	2/70 (2.9%)	2	2/66 (3%)	2
Aggression	0/64 (0%)	0	0/70 (0%)	0	1/66 (1.5%)	1
Agitation	0/64 (0%)	0	1/70 (1.4%)	1	0/66 (0%)	0
Anxiety	0/64 (0%)	0	1/70 (1.4%)	1	0/66 (0%)	0
Suicidal ideation	1/64 (1.6%)	1	0/70 (0%)	0	0/66 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Paliperidone ER 6 mg		Paliperidone ER 1.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/64 (32.8%)		29/70 (41.4%)		19/66 (28.8%)
Gastrointestinal disorders
Constipation	4/64 (6.3%)	5	6/70 (8.6%)	9	3/66 (4.5%)	3
Vomiting	0/64 (0%)	0	4/70 (5.7%)	5	1/66 (1.5%)	2
Nervous system disorders
Headache	10/64 (15.6%)	11	8/70 (11.4%)	11	5/66 (7.6%)	7
Tremor	2/64 (3.1%)	2	7/70 (10%)	7	2/66 (3%)	2
Dizziness	1/64 (1.6%)	2	2/70 (2.9%)	2	5/66 (7.6%)	5
Akathisia	1/64 (1.6%)	1	4/70 (5.7%)	4	0/66 (0%)	0
Psychiatric disorders
Insomnia	6/64 (9.4%)	11	7/70 (10%)	10	9/66 (13.6%)	11

Limitations/Caveats

No information from this study about efficacy and safety with treatment beyond 6 weeks. Study not designed to establish efficacy of 6 mg dose relative to 1.5 mg dose. No information on efficacy of paliperidone ER doses between 1.5 and 3 mg.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.