An Efficacy Study of Paliperidone for the Prevention of Relapse in Participants With Schizophrenia

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01662310
• Collaborator: (none)
• Enrollment: 201
• Locations: 15
• Arms: 3
• Duration (Months): 22
• Patients Per Site: 13.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, tolerability and safety of paliperidone extended release (ER) tablets (between 3 to 12 milligram (mg), once a day) in the prevention of relapse in schizophrenia participants.

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

Detailed Description

This is a double-blind (neither physician nor participant knows the name of the assigned drug), randomized (participants are assigned to treatment by a chance), placebo-controlled, and parallel-group study of paliperidone ER tablets. The study will consist of 6 phases: 14 days of screening phase, 8 weeks of open-label run-in phase (participants will be flexibly dosed with paliperidone ER once daily in a dose range of 3 mg to 12 mg), 6 weeks of stabilization phase (participants will continue to receive the fixed dose of paliperidone ER), double-blind (DB) phase of various length (participants will be randomly assigned in a 1:1 ratio to receive either paliperidone ER or placebo and this phase will be completed after 86 relapse events are observed or if the study is positive at the interim analysis), 6 months of open-label extension (participants who experience a relapse event or who remain relapse free for the entire duration of the double-blind phase and participants who are enrolled at the time the study is terminated, will be eligible for this phase. All participants will be treated with paliperidone ER and safety and tolerability information will be collected during this phase) phase and 6 months of follow-up phase (participants who withdraw during the DB phase for any reason other than relapse will be followed for 6 months or until they experience a relapse). Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 201 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Paliperidone Extended Release Tablets for the Prevention of Relapse in Subjects With Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paliperidone: Run-in or Stabilization phase Paliperidone extended-release (ER) oral tablet will be administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose will be increased from milligram per day (3 mg/day) after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.	Drug: Paliperidone; Paliperidone extended-release (ER) oral tablet will be administered at a starting dose of 3 milligram (mg) up to 12 mg once daily for 8 weeks in Run-in or Stabilization phase, and 3-12 mg fixed dose oral tablet will be administered in DB phase. Participants who will enter open-label extension phase will receive paliperidone as 3-12 mg per day.; Other Names: R076477
Experimental: Paliperidone: Double blind (DB) phase Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study. Participants who will experience a relapse event during the DB phase or who will remain relapse free for the entire duration of the DB phase and participants, who will be enrolled at the time the study termination will enter in open label extension phase, wherein paliperidone ER oral tablet will be administered once daily as 3 to 12 mg.	Drug: Paliperidone; Paliperidone extended-release (ER) oral tablet will be administered at a starting dose of 3 milligram (mg) up to 12 mg once daily for 8 weeks in Run-in or Stabilization phase, and 3-12 mg fixed dose oral tablet will be administered in DB phase. Participants who will enter open-label extension phase will receive paliperidone as 3-12 mg per day.; Other Names: R076477
Active Comparator: Placebo: DB phase Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study. Participants who will experience a relapse event during the DB phase or who will remain relapse free for the entire duration of the DB phase and participants, who will be enrolled at the time the study termination will enter in open label extension phase, wherein paliperidone ER oral tablet will be administered once daily as 3 to 12 mg.	Drug: Placebo; Participants who transitioned from run-in or stabilization phase will receive matching placebo to paliperidone ER once daily during DB phase of the study.

Outcome Measures

Primary Outcome Measures

1. Double Blind (DB) Phase: Median Time to Relapse [DB Baseline (Day 1 of Week 15) up to interim analysis data cut-off (24 August 2012) (Approximately 1 year)]

   A relapse is defined as any one of the following: 1. involuntary or voluntary psychiatric hospitalization 2. deliberate self-injury or violent behavior; 3. Suicidal or homicidal ideation and clinically significant aggressive behavior; 4. 25 percent (%) increase in Positive and Negative Syndrome Scale (PANSS) total score for 2 consecutive assessments for participants whose score was greater than 40 at randomization, or a 10-point increase for participants who scored less than or equal to (≤) 40 at randomization; 5. increase for 2 consecutive assessments in PANSS items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, hostility or uncooperativeness) to greater than or equal to (≥) 5 for participants who scored ≤3 at randomization, or to ≥6 for participants with initial score of 4. Independent Data Monitoring Committee performed ongoing safety monitoring during double-blind treatment and conducted the interim analysis after 61 relapse events had taken place.

Secondary Outcome Measures

1. Run-In and Stabilization Phase: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 14 [Baseline and Week 14]

   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. Double Blind (DB) Phase: Change From DB Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at DB Endpoint [DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])]

   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. Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).

3. Run-In and Stabilization Phase: Number of Participants Assessed With Categorical Scores Based on Clinical Global Impression-Severity Scale (CGI-S) [Baseline and Week 14]

   The CGI-S is a 7-point clinician-rated scale to assess severity of participant's current illness state, ranging from (1)Normal, not ill at all, (2)Borderline mentally ill, (3)Mildly ill, (4)Moderately ill, (5)Markedly ill, (6)Severely ill, (7)Among the most severely ill.

4. Double Blind (DB) Phase: Change From DB Baseline in Clinical Global Impression-Severity Scale (CGI-S) Total Score at DB Endpoint [DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])]

   CGI-S is a 7-point clinician-rated scale to assess severity of participant's current illness state, ranging from (1)Normal, not ill at all, (2)Borderline mentally ill, (3)Mildly ill, (4)Moderately ill, (5)Markedly ill, (6)Severely ill, (7)Among the most severely ill. Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).

5. Run-In and Stabilization Phase: Change From Baseline in Personal and Social Performance (PSP) Scale Total Score at Week 14 [Baseline and Week 14]

   The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty). Percentage of participants achieving improvement in PSP score by at least one category was reported.

6. Double Blind (DB) Phase: Change From DB Baseline in Personal and Social Performance (PSP) Scale Total Score at DB Endpoint [DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])]

   The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty). Percentage of participants achieving improvement in PSP score by at least one category was reported. Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).

7. Run-In and Stabilization Phase: Change From Baseline in Sleep Quality Based on Visual Analog Scale (VAS) at Week 14 [Baseline and Week 14]

   Sleep quality was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how well they slept in the previous 7 days (from 0: "very badly" to 100: "very well").

8. Double Blind (DB) Phase: Change From DB Baseline in Sleep Quality Based on Visual Analog Scale (VAS) at DB Endpoint [DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])]

   Sleep quality was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how well they slept in the previous 7 days (from 0: "very badly" to 100: "very well"). Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).

9. Run-In and Stabilization Phase: Change From Baseline in Daytime Drowsiness Based on Visual Analog Scale (VAS) at Week 14 [Baseline and Week 14]

   Daytime drowsiness was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how often they felt drowsy in the previous 7 days (from 0: "very badly" to 100: "very well").

10. Double Blind (DB) Phase: Change From DB Baseline in Daytime Drowsiness Based on Visual Analog Scale (VAS) at DB Endpoint [DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])]

    Daytime drowsiness was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how often they felt drowsy in the previous 7 days (from 0: "very badly" to 100: "very well"). Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).

11. Double Blind (DB) Phase: Median Time to Relapse (Final Analysis) [DB Baseline (Day 1 of Week 15) up to study completion (09 November 2012) (Approximately 1 year)]

    A relapse is defined as any one of the following: 1. involuntary or voluntary psychiatric hospitalization 2. deliberate self-injury or violent behavior; 3. Suicidal or homicidal ideation and clinically significant aggressive behavior; 4. 25 percent (%) increase in Positive and Negative Syndrome Scale (PANSS) total score for 2 consecutive assessments for participants whose score was greater than 40 at randomization, or a 10-point increase for participants who scored less than or equal to (≤) 40 at randomization; 5. increase for 2 consecutive assessments in PANSS items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, hostility or uncooperativeness) to greater than or equal to (≥) 5 for participants who scored ≤3 at randomization, or to ≥6 for participants with initial score of 4. Independent Data Monitoring Committee performed final analysis at the end of double-blind treatment (09 November 2012).

12. Open-label Extension (OLE) Phase: Change From OLE Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at OLE Endpoint [OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint)]

    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. Change at OLE endpoint was calculated as value at OLE endpoint (24 weeks after DB phase (26 April 2013) minus value at OLE Baseline (09 November 2012).

13. Open-label Extension (OLE) Phase: Change From OLE Baseline in Clinical Global Impression-Severity Scale (CGI-S) Total Score at OLE Endpoint [OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint)]

    CGI-S is a 7-point clinician-rated scale to assess severity of participant's current illness state, ranging from (1)Normal, not ill at all, (2)Borderline mentally ill, (3)Mildly ill, (4)Moderately ill, (5)Markedly ill, (6)Severely ill, (7)Among the most severely ill. Change at OLE endpoint was calculated as value at OLE endpoint (24 weeks after DB phase (26 April 2013) minus value at OLE Baseline (09 November 2012).

14. Open-label Extension (OLE) Phase: Change From OLE Baseline in Personal and Social Performance (PSP) Scale Total Score at OLE Endpoint [OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint)]

    The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty). Percentage of participants achieving improvement in PSP score by at least one category was reported. Change at OLE endpoint was calculated as value at OLE endpoint (24 weeks after DB phase (26 April 2013) minus value at OLE Baseline (09 November 2012).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have a diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)

• Have experienced an acute episode, with a Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 inclusive, at Screening and Baseline

• Women must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), practicing a highly effective method of birth control, if sexually active

• Men must be using a highly effective method of birth control and must not donate sperm during the study and for 3 months after receiving the last dose of study drug

• Be willing and capable to complete the questionnaires and able to take oral medications independently

Exclusion Criteria:

• Has drug dependence diagnosis according to DSM-IV (excluding nicotine and caffeine dependence) within 6 months before screening

• Participants with Crohn's disease and hepatic or renal diseases

• Has had relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular dysfunction), renal, hepatic, endocrine, or immunologic diseases

• Has had history of neuroleptic malignant syndrome (the disorder caused by antipsychotic drugs with symptoms of fever, muscle rigidity and delirium)

• Has had known or suspected Stevens Johnson Syndrome (an immune disease with symptoms of fever, sore throat, ulcers and conjunctivitis) after exposure to phenytoin, carbamazepine, barbiturates, or lamotrigine

• Had been treated with clozapine for treatment refractory or treatment resistant schizophrenia

• Has significant risk of suicide or homicidal behavior, or significant risk of deliberate self harm or harm to others

• Has taken isocarboxazid, phenelzine, selegiline and tranylcypromine within 4 weeks before screening

• Has received electroconvulsive therapy within 60 days before screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Baoding		China
2		Beijing		China
3		Changsha		China
4		Chengdu		China
5		Guangzhou		China
6		Harbin		China
7		Kunming		China
8		Nanjing		China
9		Shanghai		China
10		Taiyuan		China
11		Tianjin		China
12		Wuhan		China
13		Xi'An		China
14		Xian		China
15		Xinxiang		China

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: NCT01662310
• Other Study ID Numbers: CR100427; R076477-SCH-3041
• First Posted: Aug 10, 2012
• Last Update Posted: Sep 29, 2014
• Last Verified: Sep 1, 2014

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

Study Results

Participant Flow

Arm/Group Title	Paliperidone: Run-in or Stabilization Phase	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase	Paliperidone DB/Paliperidone Open-label (OL) Extension Phase	Placebo DB/Paliperidone OL Extension Phase
Arm/Group Description	Paliperidone extended-release (ER) oral tablet was administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose was increased from 3 milligram per day (mg/day) after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.	Participants who transitioned from run-in or stabilization phase received paliperidone at a starting dose of 3 mg up to 12 mg, fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo once daily during DB phase of the study.	Participants who transitioned from paliperidone treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.	Participants who transitioned from placebo treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.
Period Title: Run-In or Stabilization Phase
STARTED	201	0	0	0	0
COMPLETED	136	0	0	0	0
NOT COMPLETED	65	0	0	0	0
Period Title: Run-In or Stabilization Phase
STARTED	0	65	71	0	0
Treated	0	64	71	0	0
COMPLETED	0	50	66	0	0
NOT COMPLETED	0	15	5	0	0
Period Title: Run-In or Stabilization Phase
STARTED	0	0	0	47	59
COMPLETED	0	0	0	36	49
NOT COMPLETED	0	0	0	11	10

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	All the participants who were enrolled.
Overall Participants	201
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.3 (10.52)
Sex: Female, Male (Count of Participants)
Female	110 54.7%
Male	91 45.3%

Outcome Measures

1. Primary Outcome

Title	Double Blind (DB) Phase: Median Time to Relapse
Description	A relapse is defined as any one of the following: 1. involuntary or voluntary psychiatric hospitalization 2. deliberate self-injury or violent behavior; 3. Suicidal or homicidal ideation and clinically significant aggressive behavior; 4. 25 percent (%) increase in Positive and Negative Syndrome Scale (PANSS) total score for 2 consecutive assessments for participants whose score was greater than 40 at randomization, or a 10-point increase for participants who scored less than or equal to (≤) 40 at randomization; 5. increase for 2 consecutive assessments in PANSS items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, hostility or uncooperativeness) to greater than or equal to (≥) 5 for participants who scored ≤3 at randomization, or to ≥6 for participants with initial score of 4. Independent Data Monitoring Committee performed ongoing safety monitoring during double-blind treatment and conducted the interim analysis after 61 relapse events had taken place.
Time Frame	DB Baseline (Day 1 of Week 15) up to interim analysis data cut-off (24 August 2012) (Approximately 1 year)

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat DB analysis set included all the participants who were randomized into the DB phase and who received at least one dose of DB study medication up to interim analysis cut-off date (24-Aug-2012). "N" (number of participants analyzed) signifies the participants evaluable for this measure.

Arm/Group Title	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase
Arm/Group Description	Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study.
Measure Participants	59	65
Median (95% Confidence Interval) [Days]	NA	49.0

2. Secondary Outcome

Title	Run-In and Stabilization Phase: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 14
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 Week 14

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (RI/ST) analysis set included all the participants who received at least one dose of study medication in run-in phase or stabilization phase. "n" signifies those participants who were evaluated for this measure at the specified time point. Last observation carried forward (LOCF) method was used to impute missing values.

Arm/Group Title	Paliperidone: Run-in or Stabilization Phase
Arm/Group Description	Paliperidone extended-release (ER) oral tablet was administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose was increased from 3 mg/day after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.
Measure Participants	201
Baseline (n=201)	89.5 (12.48)
Change at Week 14 (n=200)	-30.8 (18.55)

3. Secondary Outcome

Title	Double Blind (DB) Phase: Change From DB Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at DB Endpoint
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. Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).
Time Frame	DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat DB analysis set included all the participants who were randomized into the DB phase and who received at least one dose of DB study medication. LOCF method was used to impute missing values.

Arm/Group Title	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase
Arm/Group Description	Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study.
Measure Participants	64	71
Baseline	53.4 (9.71)	51.5 (9.50)
Change at DB endpoint	2.0 (12.67)	16.9 (16.16)

4. Secondary Outcome

Title	Run-In and Stabilization Phase: Number of Participants Assessed With Categorical Scores Based on Clinical Global Impression-Severity Scale (CGI-S)
Description	The CGI-S is a 7-point clinician-rated scale to assess severity of participant's current illness state, ranging from (1)Normal, not ill at all, (2)Borderline mentally ill, (3)Mildly ill, (4)Moderately ill, (5)Markedly ill, (6)Severely ill, (7)Among the most severely ill.
Time Frame	Baseline and Week 14

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (RI/ST) analysis set included all the participants who received at least one dose of study medication in run-in phase or stabilization phase. "n" signifies those participants who were evaluated for this measure at the specified time point.

Arm/Group Title	Paliperidone: Run-in or Stabilization Phase
Arm/Group Description	Paliperidone extended-release (ER) oral tablet was administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose was increased from 3 mg/day after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.
Measure Participants	201
Not ill: Baseline (n=201)	0 (12.48) 0%
Not ill: Week 14 (n= 135)	2 (18.49) 1%
Very Mild: Baseline (n= 201)	0 0%
Very Mild: Week 14 (n= 135)	37 18.4%
Mild: Baseline (n= 201)	3 1.5%
Mild: Week 14 (n= 135)	65 32.3%
Moderate: Baseline (n= 201)	41 20.4%
Moderate: Week 14 (n= 135)	27 13.4%
Marked: Baseline (n= 201)	91 45.3%
Marked: Week 14 (n= 135)	4 2%
Severe: Baseline (n= 201)	66 32.8%
Severe: Week 14 (n= 135)	0 0%
Extremely Severe: Baseline (n= 201)	0 0%
Extremely Severe: Week 14 (n= 135)	0 0%

5. Secondary Outcome

Title	Double Blind (DB) Phase: Change From DB Baseline in Clinical Global Impression-Severity Scale (CGI-S) Total Score at DB Endpoint
Description	CGI-S is a 7-point clinician-rated scale to assess severity of participant's current illness state, ranging from (1)Normal, not ill at all, (2)Borderline mentally ill, (3)Mildly ill, (4)Moderately ill, (5)Markedly ill, (6)Severely ill, (7)Among the most severely ill. Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).
Time Frame	DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat DB analysis set included all the participants who were randomized into the DB phase and who received at least one dose of DB study medication.

Arm/Group Title	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase
Arm/Group Description	Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study.
Measure Participants	64	71
Baseline	3.0 (0.88)	2.9 (0.70)
Change at DB endpoint	0.1 (0.91)	1.1 (1.11)

6. Secondary Outcome

Title	Run-In and Stabilization Phase: Change From Baseline in Personal and Social Performance (PSP) Scale Total Score at Week 14
Description	The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty). Percentage of participants achieving improvement in PSP score by at least one category was reported.
Time Frame	Baseline and Week 14

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (RI/ST) analysis set included all the participants who received at least one dose of study medication in run-in phase or stabilization phase. "n" signifies those participants who were evaluated for this measure at the specified time point. LOCF method was used to impute missing values.

Arm/Group Title	Paliperidone: Run-in or Stabilization Phase
Arm/Group Description	Paliperidone extended-release (ER) oral tablet was administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose was increased from 3 mg/day after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.
Measure Participants	201
Baseline (n=201)	43.6 (13.96)
Change at Week 14 (n=200)	20.9 (17.55)

7. Secondary Outcome

Title	Double Blind (DB) Phase: Change From DB Baseline in Personal and Social Performance (PSP) Scale Total Score at DB Endpoint
Description	The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty). Percentage of participants achieving improvement in PSP score by at least one category was reported. Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).
Time Frame	DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat DB analysis set included all the participants who were randomized into the DB phase and who received at least one dose of DB study medication.

Arm/Group Title	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase
Arm/Group Description	Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study.
Measure Participants	64	71
Baseline	69.3 (11.17)	69.9 (9.37)
Change at DB Endpoint	-2.9 (12.87)	-10.7 (14.99)

8. Secondary Outcome

Title	Run-In and Stabilization Phase: Change From Baseline in Sleep Quality Based on Visual Analog Scale (VAS) at Week 14
Description	Sleep quality was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how well they slept in the previous 7 days (from 0: "very badly" to 100: "very well").
Time Frame	Baseline and Week 14

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (RI/ST) analysis set included all the participants who received at least one dose of study medication in run-in phase or stabilization phase. "n" signifies those participants who were evaluated for this measure at the specified time point. LOCF method was used to impute missing values.

Arm/Group Title	Paliperidone: Run-in or Stabilization Phase
Arm/Group Description	Paliperidone extended-release (ER) oral tablet was administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose was increased from 3 mg/day after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.
Measure Participants	201
Baseline (n=201)	63.4 (24.60)
Change at Week 14 (n=192)	12.1 (29.13)

9. Secondary Outcome

Title	Double Blind (DB) Phase: Change From DB Baseline in Sleep Quality Based on Visual Analog Scale (VAS) at DB Endpoint
Description	Sleep quality was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how well they slept in the previous 7 days (from 0: "very badly" to 100: "very well"). Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).
Time Frame	DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat DB analysis set included all the participants who were randomized into the DB phase and who received at least one dose of DB study medication. "n" signifies those participants who were evaluated for this measure at the specified time point.

Arm/Group Title	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase
Arm/Group Description	Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study.
Measure Participants	64	71
Baseline (n= 64, 71)	77.5 (20.45)	81.9 (14.82)
Change at DB Endpoint (n= 60, 69)	-3.8 (20.02)	-22.4 (27.88)

10. Secondary Outcome

Title	Run-In and Stabilization Phase: Change From Baseline in Daytime Drowsiness Based on Visual Analog Scale (VAS) at Week 14
Description	Daytime drowsiness was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how often they felt drowsy in the previous 7 days (from 0: "very badly" to 100: "very well").
Time Frame	Baseline and Week 14

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (RI/ST) analysis set included all the participants who received at least one dose of study medication in run-in phase or stabilization phase. "n" signifies those participants who were evaluated for this measure at the specified time point. LOCF method was used to impute missing values.

Arm/Group Title	Paliperidone: Run-in or Stabilization Phase
Arm/Group Description	Paliperidone extended-release (ER) oral tablet was administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose was increased from 3 mg/day after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.
Measure Participants	201
Baseline (n=201)	32.8 (27.03)
Change at Week 14 (n=192)	-7.3 (33.73)

11. Secondary Outcome

Title	Double Blind (DB) Phase: Change From DB Baseline in Daytime Drowsiness Based on Visual Analog Scale (VAS) at DB Endpoint
Description	Daytime drowsiness was assessed by an 11-point visual analog scale that rates how well participants slept. Participants indicated on the scale (from 0 to 100 millimeter) how often they felt drowsy in the previous 7 days (from 0: "very badly" to 100: "very well"). Change at DB endpoint was calculated as value at interim analysis data cut-off (09 November 2012) minus value at DB Baseline (Day 1 of week 15).
Time Frame	DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year])

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat DB analysis set included all the participants who were randomized into the DB phase and who received at least one dose of DB study medication. "n" signifies those participants who were evaluated for this measure at the specified time point.

Arm/Group Title	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase
Arm/Group Description	Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study.
Measure Participants	64	71
Baseline (n= 64, 71)	22.9 (24.24)	24.4 (22.93)
Change at DB Endpoint (n= 60, 69)	3.1 (23.18)	1.2 (28.50)

12. Secondary Outcome

Title	Double Blind (DB) Phase: Median Time to Relapse (Final Analysis)
Description	A relapse is defined as any one of the following: 1. involuntary or voluntary psychiatric hospitalization 2. deliberate self-injury or violent behavior; 3. Suicidal or homicidal ideation and clinically significant aggressive behavior; 4. 25 percent (%) increase in Positive and Negative Syndrome Scale (PANSS) total score for 2 consecutive assessments for participants whose score was greater than 40 at randomization, or a 10-point increase for participants who scored less than or equal to (≤) 40 at randomization; 5. increase for 2 consecutive assessments in PANSS items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, hostility or uncooperativeness) to greater than or equal to (≥) 5 for participants who scored ≤3 at randomization, or to ≥6 for participants with initial score of 4. Independent Data Monitoring Committee performed final analysis at the end of double-blind treatment (09 November 2012).
Time Frame	DB Baseline (Day 1 of Week 15) up to study completion (09 November 2012) (Approximately 1 year)

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat DB analysis set included all the participants who were randomized into the DB phase and who received at least one dose of DB study medication up to final analysis cut-off date (09-Nov-2012).

Arm/Group Title	Paliperidone: Double Blind (DB) Phase	Placebo: DB Phase
Arm/Group Description	Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.	Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study.
Measure Participants	64	71
Median (95% Confidence Interval) [Days]	NA	52.0

13. Secondary Outcome

Title	Open-label Extension (OLE) Phase: Change From OLE Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at OLE Endpoint
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. Change at OLE endpoint was calculated as value at OLE endpoint (24 weeks after DB phase (26 April 2013) minus value at OLE Baseline (09 November 2012).
Time Frame	OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint)

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) OLE analysis set included all participants who received at least one dose of OLE medication as recorded on the electronic case report form (eCRF). LOCF method was used to impute missing values. "N" (number of participants analyzed) signifies the participants evaluable for this measure.

Arm/Group Title	Paliperidone DB/Paliperidone Open-label (OL) Extension Phase	Placebo DB/Paliperidone OL Extension Phase
Arm/Group Description	Participants who transitioned from paliperidone treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.	Participants who transitioned from placebo treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.
Measure Participants	46	59
Baseline	56.5 (14.86)	67.2 (14.67)
Change at OLE endpoint	-3.9 (11.30)	-15.4 (12.41)

14. Secondary Outcome

Title	Open-label Extension (OLE) Phase: Change From OLE Baseline in Clinical Global Impression-Severity Scale (CGI-S) Total Score at OLE Endpoint
Description	CGI-S is a 7-point clinician-rated scale to assess severity of participant's current illness state, ranging from (1)Normal, not ill at all, (2)Borderline mentally ill, (3)Mildly ill, (4)Moderately ill, (5)Markedly ill, (6)Severely ill, (7)Among the most severely ill. Change at OLE endpoint was calculated as value at OLE endpoint (24 weeks after DB phase (26 April 2013) minus value at OLE Baseline (09 November 2012).
Time Frame	OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint)

Outcome Measure Data

Analysis Population Description

The ITT OLE analysis set included all participants who received at least one dose of OLE medication as recorded on the electronic case report form (eCRF). LOCF method was used to impute missing values. "N" (number of participants analyzed) signifies the participants evaluable for this measure.

Arm/Group Title	Paliperidone DB/Paliperidone Open-label (OL) Extension Phase	Placebo DB/Paliperidone OL Extension Phase
Arm/Group Description	Participants who transitioned from paliperidone treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.	Participants who transitioned from placebo treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.
Measure Participants	46	59
Baseline	3.1 (1.02)	3.9 (0.98)
Change at OLE endpoint	-0.2 (0.78)	-0.9 (0.97)

15. Secondary Outcome

Title	Open-label Extension (OLE) Phase: Change From OLE Baseline in Personal and Social Performance (PSP) Scale Total Score at OLE Endpoint
Description	The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty). Percentage of participants achieving improvement in PSP score by at least one category was reported. Change at OLE endpoint was calculated as value at OLE endpoint (24 weeks after DB phase (26 April 2013) minus value at OLE Baseline (09 November 2012).
Time Frame	OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint)

Outcome Measure Data

Analysis Population Description

The ITT OLE analysis set included all participants who received at least one dose of OLE medication as recorded on the electronic case report form (eCRF). LOCF method was used to impute missing values. "N" (number of participants analyzed) signifies the participants evaluable for this measure.

Arm/Group Title	Paliperidone DB/Paliperidone Open-label (OL) Extension Phase	Placebo DB/Paliperidone OL Extension Phase
Arm/Group Description	Participants who transitioned from paliperidone treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.	Participants who transitioned from placebo treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.
Measure Participants	46	59
Baseline	66.8 (15.68)	60.6 (15.63)
Change at OLE endpoint	10.88 (3.1)	10.7 (14.01)

Adverse Events

Adverse Event Reporting Description	Safety analysis set included all the participants who were randomized into the double-blind phase and received at least 1 dose of double-blind medication.
Arm/Group Title	Paliperidone: Run-in or Stabilization Phase		Paliperidone: Double Blind (DB) Phase		Placebo: DB Phase		Paliperidone DB/Paliperidone Open-label (OL) Extension Phase		Placebo DB/Paliperidone OL Extension Phase
Arm/Group Description	Paliperidone extended-release (ER) oral tablet was administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose was increased from 3 mg/day after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.		Participants who transitioned from run-in or stabilization phase received paliperidone at a starting dose of 3 mg up to 12 mg, fixed dose of paliperidone ER oral tablet once daily during DB phase of the study.		Participants who transitioned from run-in or stabilization phase received matching placebo once daily during DB phase of the study.		Participants who transitioned from paliperidone treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.		Participants who transitioned from placebo treatment group in DB phase (that is participants who experienced a relapse event during the DB phase or who remained relapse free for the entire duration of the double-blind phase and participants, who were enrolled at the time the study was terminated), entered open label extension phase, wherein paliperidone ER oral tablet was administered once daily as 3 to 12 mg.
All Cause Mortality
	Paliperidone: Run-in or Stabilization Phase		Paliperidone: Double Blind (DB) Phase		Placebo: DB Phase		Paliperidone DB/Paliperidone Open-label (OL) Extension Phase		Placebo DB/Paliperidone OL Extension 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
	Paliperidone: Run-in or Stabilization Phase		Paliperidone: Double Blind (DB) Phase		Placebo: DB Phase		Paliperidone DB/Paliperidone Open-label (OL) Extension Phase		Placebo DB/Paliperidone OL Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/201 (1%)		2/64 (3.1%)		8/71 (11.3%)		2/47 (4.3%)		0/59 (0%)
Psychiatric disorders
Aggression	0/201 (0%)		0/64 (0%)		1/71 (1.4%)		0/47 (0%)		0/59 (0%)
Completed Suicide	0/201 (0%)		0/64 (0%)		1/71 (1.4%)		1/47 (2.1%)		0/59 (0%)
Hallucination, Auditory	0/201 (0%)		0/64 (0%)		1/71 (1.4%)		0/47 (0%)		0/59 (0%)
Psychotic Disorder	1/201 (0.5%)		0/64 (0%)		0/71 (0%)		0/47 (0%)		0/59 (0%)
Schizophrenia	1/201 (0.5%)		1/64 (1.6%)		5/71 (7%)		1/47 (2.1%)		0/59 (0%)
Suicide Attempt	0/201 (0%)		1/64 (1.6%)		0/71 (0%)		0/47 (0%)		0/59 (0%)
Other (Not Including Serious) Adverse Events
	Paliperidone: Run-in or Stabilization Phase		Paliperidone: Double Blind (DB) Phase		Placebo: DB Phase		Paliperidone DB/Paliperidone Open-label (OL) Extension Phase		Placebo DB/Paliperidone OL Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	141/201 (70.1%)		12/64 (18.8%)		12/71 (16.9%)		6/47 (12.8%)		14/59 (23.7%)
Cardiac disorders
Tachycardia	12/201 (6%)		0/64 (0%)		1/71 (1.4%)		0/47 (0%)		0/59 (0%)
Ear and labyrinth disorders
Vertigo	19/201 (9.5%)		1/64 (1.6%)		1/71 (1.4%)		0/47 (0%)		0/59 (0%)
Eye disorders
Vision Blurred	13/201 (6.5%)		1/64 (1.6%)		0/71 (0%)		0/47 (0%)		0/59 (0%)
Gastrointestinal disorders
Constipation	19/201 (9.5%)		1/64 (1.6%)		0/71 (0%)		2/47 (4.3%)		2/59 (3.4%)
Nausea	12/201 (6%)		2/64 (3.1%)		1/71 (1.4%)		0/47 (0%)		0/59 (0%)
Infections and infestations
Nasopharyngitis	17/201 (8.5%)		0/64 (0%)		2/71 (2.8%)		1/47 (2.1%)		3/59 (5.1%)
Upper Respiratory Tract Infection	12/201 (6%)		1/64 (1.6%)		1/71 (1.4%)		1/47 (2.1%)		1/59 (1.7%)
Investigations
Weight Increased	13/201 (6.5%)		1/64 (1.6%)		1/71 (1.4%)		0/47 (0%)		2/59 (3.4%)
Nervous system disorders
Akathisia	52/201 (25.9%)		3/64 (4.7%)		0/71 (0%)		1/47 (2.1%)		3/59 (5.1%)
Dyskinesia	11/201 (5.5%)		0/64 (0%)		1/71 (1.4%)		0/47 (0%)		0/59 (0%)
Dystonia	11/201 (5.5%)		0/64 (0%)		0/71 (0%)		0/47 (0%)		1/59 (1.7%)
Headache	11/201 (5.5%)		1/64 (1.6%)		0/71 (0%)		1/47 (2.1%)		1/59 (1.7%)
Hypertonia	14/201 (7%)		0/64 (0%)		0/71 (0%)		0/47 (0%)		0/59 (0%)
Somnolence	19/201 (9.5%)		0/64 (0%)		0/71 (0%)		1/47 (2.1%)		3/59 (5.1%)
Tremor	24/201 (11.9%)		2/64 (3.1%)		0/71 (0%)		0/47 (0%)		0/59 (0%)
Psychiatric disorders
Insomnia	21/201 (10.4%)		1/64 (1.6%)		6/71 (8.5%)		1/47 (2.1%)		1/59 (1.7%)
Restlessness	12/201 (6%)		1/64 (1.6%)		0/71 (0%)		0/47 (0%)		2/59 (3.4%)

Limitations/Caveats

Independent Data Monitoring Committee (IDMC) conducted an interim analysis after 61st relapse in double-blind (DB) phase and DB phase completed on 09-Nov-2012 based on positive results of interim analysis.

More Information

Certain Agreements

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

If an Investigator wishes to publish information from study, a copy of the manuscript must be provided to the Sponsor for review at least 60 days before submission for publication or presentation. If requested by the Sponsor, investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application. Investigators will not publish data derived from individual site until Sponsor confirms there will be no multi-center study publication.