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A Study to Evaluate Effectiveness and Safety of ER OROS Paliperidone in Patients With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00396565
Recruitment Status : Completed
First Posted : November 7, 2006
Results First Posted : July 3, 2012
Last Update Posted : April 29, 2014
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: ER OROS paliperidone
Drug: Placebo
Drug: Olanzapine
Enrollment 394
Recruitment Details  
Pre-assignment Details Informed Consent was obtained from 394 patients. The actual number of patients randomized in the study was 321. 2 subjects discontinued before treatment. 319 subjects were treated and analyzed for safety. 318 subjects were analyzed for baseline characteristics and efficacy.
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks Two placebo tablets once daily for 6 weeks Four olanzapine 2.5 mg tablets once daily for 6 weeks
Period Title: Overall Study
Started 136 138 47
Completed 88 47 30
Not Completed 48 91 17
Reason Not Completed
Physician Decision             3             1             2
Adverse Event             5             13             3
Withdrawal by Subject             8             13             1
Lack of Efficacy             32             64             11
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine Total
Hide Arm/Group Description Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks Two placebo tablets once daily for 6 weeks Four olanzapine 2.5 mg tablets once daily for 6 weeks Total of all reporting groups
Overall Number of Baseline Participants 134 138 46 318
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 134 participants 138 participants 46 participants 318 participants
44.0  (14.7) 46.2  (15.1) 46.2  (13.2) 45.3  (14.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 134 participants 138 participants 46 participants 318 participants
Female
64
  47.8%
66
  47.8%
27
  58.7%
157
  49.4%
Male
70
  52.2%
72
  52.2%
19
  41.3%
161
  50.6%
Total Positive and Negative Syndrome Scale (PANSS) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 134 participants 138 participants 46 participants 318 participants
92.0  (12.9) 91.0  (11.2) 94.1  (12.6) 91.9  (12.2)
[1]
Measure Description: PANSS is a medical scale that assesses various symptoms of schizophrenia. Symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).
1.Primary Outcome
Title Change From Baseline in the Total Positive and Negative Syndrome Scale (PANSS).
Hide Description PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set excludes subjects who didn’t receive test drug or didn't have post-treatment efficacy data. The Olanzapine (OLZ) group was set as an active drug group to examine clinical position of paliperidone (PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description:
Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks
Two placebo tablets once daily for 6 weeks
Four olanzapine 2.5 mg tablets once daily for 6 weeks
Overall Number of Participants Analyzed 134 138 46
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-9.1  (18.39) 3.8  (18.88) -9.9  (16.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Extended Release (ER) (JNS007ER), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and baseline score as a covariate
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -12.7
Confidence Interval 95%
-17.16 to -8.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.26
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score
Hide Description The PANSS Positive Subscale assesses seven positive-symptoms of schizophrenia. Positive symptoms refer to an excess or distortion 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 and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set excludes subjects who didn’t receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description:
Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks
Two placebo tablets once daily for 6 weeks
Four olanzapine 2.5 mg tablets once daily for 6 weeks
Overall Number of Participants Analyzed 134 138 46
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-2.6  (5.69) 1.6  (5.53) -2.4  (5.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Extended Release (ER) (JNS007ER), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and with baseline score as a covariate.
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -3.8
Confidence Interval 95%
-5.17 to -2.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.68
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score
Hide Description The PANSS Negative Subscale assesses seven 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 and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set excludes subjects who didn’t receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description:
Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks
Two placebo tablets once daily for 6 weeks
Four olanzapine 2.5 mg tablets once daily for 6 weeks
Overall Number of Participants Analyzed 134 138 46
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-2.4  (5.05) 0.0  (5.02) -2.8  (4.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Extended Release (ER) (JNS007ER), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor and with baseline score as a covariate
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -2.5
Confidence Interval 95%
-3.71 to -1.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.60
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score
Hide Description The PANSS General Psychopathology Subscale Score assesses 16 general psychopathology symptoms. The symptoms are rated on a 7-point scale, with a range of 16 (absent) to 112 (extreme psychopathology).
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set excludes subjects who didn’t receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description:
Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks
Two placebo tablets once daily for 6 weeks
Four olanzapine 2.5 mg tablets once daily for 6 weeks
Overall Number of Participants Analyzed 134 138 46
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-4.1  (9.52) 2.2  (10.71) -4.7  (9.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Extended Release (ER) (JNS007ER), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor, and with baseline score as a covariate
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -6.2
Confidence Interval 95%
-8.58 to -3.80
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.21
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Proportion of Responders (≥30% Decrease in Total Positive and Negative Syndrome Scale [PANSS])
Hide Description Responders are subjects with 30% or more reduction from baseline in total PANSS score. PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set excludes subjects who didn’t receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description:
Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks
Two placebo tablets once daily for 6 weeks
Four olanzapine 2.5 mg tablets once daily for 6 weeks
Overall Number of Participants Analyzed 134 138 46
Measure Type: Number
Unit of Measure: Percentage of participants
25.4 9.4 26.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Extended Release (ER) (JNS007ER), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Clinical Global Impression Scale (CGI-S)
Hide Description The CGI-S rating scale is a 7-point global assessment with scores as follows: 1 – Not ill, 2 – Very Mild, 3 – Mild, 4 – Moderate, 5 – Marked, 6 – Severe, and 7 – Extremely Severe.
Time Frame Baseline and 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set excludes subjects who didn’t receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description:
Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks
Two placebo tablets once daily for 6 weeks
Four olanzapine 2.5 mg tablets once daily for 6 weeks
Overall Number of Participants Analyzed 134 138 46
Mean (Standard Error)
Unit of Measure: scores on a scale
-0.4  (0.09) 0.2  (0.09) -0.3  (0.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Extended Release (ER) (JNS007ER), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment as a factor, and baseline score as a covariate
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.6
Confidence Interval 95%
-0.84 to -0.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.13
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Hide Arm/Group Description Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks Two placebo tablets once daily for 6 weeks Four olanzapine 2.5 mg tablets once daily for 6 weeks
All-Cause Mortality
Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/134 (2.99%)   1/138 (0.72%)   2/47 (4.26%) 
Infections and infestations       
pneumonia  1  1/134 (0.75%)  0/138 (0.00%)  0/47 (0.00%) 
Psychiatric disorders       
schizophrenia  1  3/134 (2.24%)  1/138 (0.72%)  1/47 (2.13%) 
mood altered  1  0/134 (0.00%)  0/138 (0.00%)  1/47 (2.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA/J v10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Paliperidone Extended Release (ER) (JNS007ER) Placebo Olanzapine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   109/134 (81.34%)   110/138 (79.71%)   40/47 (85.11%) 
Cardiac disorders       
Tachycardia  1  1/134 (0.75%)  0/138 (0.00%)  3/47 (6.38%) 
Gastrointestinal disorders       
Constipation  1  11/134 (8.21%)  2/138 (1.45%)  5/47 (10.64%) 
General disorders       
Pyrexia  1  5/134 (3.73%)  3/138 (2.17%)  3/47 (6.38%) 
Thirst  1  2/134 (1.49%)  2/138 (1.45%)  5/47 (10.64%) 
Hepatobiliary disorders       
Hepatic function abnormal  1  7/134 (5.22%)  1/138 (0.72%)  1/47 (2.13%) 
Infections and infestations       
Nasopharyngitis  1  14/134 (10.45%)  11/138 (7.97%)  1/47 (2.13%) 
Investigations       
Blood creatine phosphokinase increased  1  9/134 (6.72%)  8/138 (5.80%)  2/47 (4.26%) 
Weight increased  1  8/134 (5.97%)  0/138 (0.00%)  5/47 (10.64%) 
Blood triglycerides increased  1  9/134 (6.72%)  0/138 (0.00%)  3/47 (6.38%) 
Basophil count increased  1  1/134 (0.75%)  8/138 (5.80%)  0/47 (0.00%) 
White blood cell count increased  1  2/134 (1.49%)  1/138 (0.72%)  3/47 (6.38%) 
Gamma-glutamyltransferase increased  1  1/134 (0.75%)  0/138 (0.00%)  3/47 (6.38%) 
Nervous system disorders       
Extrapyramidal disorder  1  10/134 (7.46%)  1/138 (0.72%)  1/47 (2.13%) 
Somnolence  1  3/134 (2.24%)  1/138 (0.72%)  8/47 (17.02%) 
Dizziness  1  1/134 (0.75%)  2/138 (1.45%)  3/47 (6.38%) 
Psychiatric disorders       
schizophrenia  1  22/134 (16.42%)  59/138 (42.75%)  11/47 (23.40%) 
Insomnia  1  15/134 (11.19%)  14/138 (10.14%)  5/47 (10.64%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA/J v10.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Without prior notification to the sponsor, the PI cannnot dislose trial results and related documents of trials to a third party.
Results Point of Contact
Name/Title: Director of Clinical R&D Dept. 3
Organization: Janssen Pharmaceutical K.K.
Phone: 81-3-4411-5652 ext 10118
Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT00396565     History of Changes
Other Study ID Numbers: CR012625
JNS007ER-JPN-S31 ( Other Identifier: Janssen Pharmaceutical K.K., Japan )
First Submitted: November 3, 2006
First Posted: November 7, 2006
Results First Submitted: March 27, 2012
Results First Posted: July 3, 2012
Last Update Posted: April 29, 2014