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A Comparative Study of Paliperidone Palmitate and Risperidone Long Acting Injection (LAI) in Participants With Schizophrenia

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ClinicalTrials.gov Identifier: NCT00604279
Recruitment Status : Completed
First Posted : January 30, 2008
Results First Posted : July 10, 2013
Last Update Posted : July 10, 2013
Sponsor:
Information provided by (Responsible Party):
Xian-Janssen Pharmaceutical Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: Paliperidone palmitate (R092670)
Drug: Risperidone
Enrollment 452
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Hide Arm/Group Description Paliperidone palmitate (R092670) suspension for intramuscular (directly into a muscle) injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion. Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
Period Title: Overall Study
Started 229 223
Completed 165 185
Not Completed 64 38
Reason Not Completed
Lack of Efficacy             22             9
Lost to Follow-up             9             14
Pregnancy             2             0
Protocol Violation             3             1
Withdrawal by Subject             16             5
Adverse Event             4             5
Other             8             4
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI) Total
Hide Arm/Group Description Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion. Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64. Total of all reporting groups
Overall Number of Baseline Participants 229 223 452
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 229 participants 223 participants 452 participants
32  (10.75) 31.5  (11.03) 31.7  (10.88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 229 participants 223 participants 452 participants
Female
142
  62.0%
129
  57.8%
271
  60.0%
Male
87
  38.0%
94
  42.2%
181
  40.0%
Age Categorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 229 participants 223 participants 452 participants
18-25 Years 87 92 179
26-50 Years 125 114 239
51-65 Years 17 17 34
>65 Years 0 0 0
<18 Years 0 0 0
1.Primary Outcome
Title Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 92 or Early Withdrawal
Hide Description The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 (absent) to 210 (extreme psychopathology). Higher change scores indicate worsening.
Time Frame Baseline, Day 92 or early withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Analysis Set included participants who received at least 2 injections of study medication had minimum 5 weeks of exposure to study treatment; had baseline and at least 1 post randomization measurement for primary efficacy variable and who did not have major protocol violations.
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Hide Arm/Group Description:
Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion.
Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
Overall Number of Participants Analyzed 205 208
Mean (Standard Deviation)
Unit of Measure: Units on scale
Baseline 82.1  (11.95) 84.4  (12.69)
Change at Day 92 or Early Withdrawal -23.6  (16.28) -26.9  (15.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Risperidone Long Acting Injection (LAI)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The predetermined margin for non-inferiority of paliperidone palmitate was 5.5 points
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments Analysis of covariance (ANCOVA) model with treatment as a factor, and baseline value as a covariate was used.
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -2.3
Confidence Interval 95%
-5.20 to 0.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.48
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Personal and Social Performance (PSP) Score at Day 92 or Early Withdrawal
Hide Description This PSP assesses the degree of a participant’s dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 4, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; <= 30, functioning so poorly as to require intensive supervision.
Time Frame Baseline, Day 92 or early withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Analysis Set. Here "N" (Number of Participants Analyzed) represents number of participants who were evaluable for this measure.
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Hide Arm/Group Description:
Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion.
Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
Overall Number of Participants Analyzed 184 190
Mean (Standard Deviation)
Unit of Measure: Units on scale
Baseline 47.8  (12.42) 45.3  (11.29)
Change at Day 92 or Early Withdrawal 16.8  (14.76) 18.6  (13.92)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Risperidone Long Acting Injection (LAI)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments Analysis of covariance (ANCOVA) model with treatment as a factor, and baseline value as a covariate was used.
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 0.5
Confidence Interval 95%
-2.14 to 3.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.34
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 92 or Early Withdrawal
Hide Description The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher change scores indicate worsening.
Time Frame Baseline, Day 92 or early withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Analysis Set. Here "N" (Number of Participants Analyzed) represents number of participants who were evaluable for this measure.
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Hide Arm/Group Description:
Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion.
Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
Overall Number of Participants Analyzed 204 207
Mean (Standard Deviation)
Unit of Measure: Units on scale
Baseline 4.9  (0.82) 5.0  (0.81)
Change at Day 92 or Early Withdrawal -1.5  (1.24) -1.7  (1.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Risperidone Long Acting Injection (LAI)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments Analysis of covariance (ANCOVA) model with treatment as a factor, and baseline value as a covariate was used.
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -0.1
Confidence Interval 95%
-0.33 to 0.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal
Hide Description The self-administered sleep VAS scale (0-100 millimeter [mm]) rates quality of sleep (QoS) and daytime drowsiness (DD). Participants indicate mark on the scale to represent how well they have slept in the previous 7 days, score ranges from 0 mm (very badly) to 100 mm (very well); and how often they have felt drowsy within the previous 7 days, from 0 mm (not at all) to 100 mm (all the time).
Time Frame Baseline, Day 92 or early withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Analysis Set.
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Hide Arm/Group Description:
Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion.
Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
Overall Number of Participants Analyzed 205 208
Mean (Standard Deviation)
Unit of Measure: millimeter (mm)
QoS, Baseline 64.1  (25.40) 66.6  (24.22)
QoS, Change at Day 92 or Early Withdrawal 8.2  (26.95) 10.0  (26.18)
DD, Baseline 29.9  (25.25) 29.6  (23.50)
DD, Change at Day 92 or Early Withdrawal -4.1  (27.26) -4.9  (24.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Risperidone Long Acting Injection (LAI)
Comments Statistical Analysis for Quality of sleep
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments Analysis of covariance (ANCOVA) model with treatment as a factor, and baseline value as a covariate was used.
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value 3.4
Confidence Interval 95%
-0.67 to 7.50
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Risperidone Long Acting Injection (LAI)
Comments Statistical Analysis for Daytime drowsiness
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments Analysis of covariance (ANCOVA) model with treatment as a factor, and baseline value as a covariate was used.
Method of Estimation Estimation Parameter Least Square Mean Difference
Estimated Value -1.1
Confidence Interval 95%
-5.04 to 2.90
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.02
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Who Responded to PANSS Total Score at Day 92 or Early Withdrawal
Hide Description A responder is defined as a participant who improved from baseline in the PANSS total score by 30 percent or more.
Time Frame Day 92 or early withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Analysis Set.
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Hide Arm/Group Description:
Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion.
Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
Overall Number of Participants Analyzed 205 208
Measure Type: Number
Unit of Measure: Percentage of participants
70.7 78.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Risperidone Long Acting Injection (LAI)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Point estimate of relative risk
Estimated Value 0.9
Confidence Interval 95%
0.81 to 1.01
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Hide Arm/Group Description Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator’s discretion. Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
All-Cause Mortality
Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Affected / at Risk (%) Affected / at Risk (%)
Total   3/229 (1.31%)   8/223 (3.59%) 
Gastrointestinal disorders     
Nausea * 1  0/229 (0.00%)  1/223 (0.45%) 
Vomiting * 1  0/229 (0.00%)  1/223 (0.45%) 
Injury, poisoning and procedural complications     
Lumbar vertebral fracture * 1  0/229 (0.00%)  1/223 (0.45%) 
Overdose * 1  0/229 (0.00%)  1/223 (0.45%) 
Road traffic accident * 1  0/229 (0.00%)  1/223 (0.45%) 
Nervous system disorders     
Cerebral infarction * 1  1/229 (0.44%)  0/223 (0.00%) 
Convulsion * 1  0/229 (0.00%)  1/223 (0.45%) 
Psychiatric disorders     
Completed suicide * 1  0/229 (0.00%)  1/223 (0.45%) 
Psychiatric symptom * 1  1/229 (0.44%)  0/223 (0.00%) 
Schizophrenia * 1  1/229 (0.44%)  0/223 (0.00%) 
Renal and urinary disorders     
Hydronephrosis * 1  0/229 (0.00%)  1/223 (0.45%) 
Nephrolithiasis * 1  0/229 (0.00%)  1/223 (0.45%) 
Social circumstances     
Refusal of treatment by patient * 1  0/229 (0.00%)  1/223 (0.45%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Paliperidone Palmitate Risperidone Long Acting Injection (LAI)
Affected / at Risk (%) Affected / at Risk (%)
Total   115/229 (50.22%)   127/223 (56.95%) 
Gastrointestinal disorders     
Constipation * 1  17/229 (7.42%)  12/223 (5.38%) 
Infections and infestations     
Upper respiratory tract infection * 1  18/229 (7.86%)  13/223 (5.83%) 
Investigations     
Blood prolactin increased * 1  17/229 (7.42%)  12/223 (5.38%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal stiffness * 1  10/229 (4.37%)  16/223 (7.17%) 
Nervous system disorders     
Akathisia * 1  30/229 (13.10%)  44/223 (19.73%) 
Bradykinesia * 1  16/229 (6.99%)  9/223 (4.04%) 
Tremor * 1  24/229 (10.48%)  40/223 (17.94%) 
Psychiatric disorders     
Anxiety * 1  10/229 (4.37%)  13/223 (5.83%) 
Insomnia * 1  41/229 (17.90%)  30/223 (13.45%) 
Restlessness * 1  16/229 (6.99%)  22/223 (9.87%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 12.0
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.
The disclosure restriction on the PI is that the sponsor can review results communications prior to publication and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The paper that incorporates confidential information requires Sponsor’s written consent. PI will withhold publication for up to an additional 60 days to allow for filing of a patent application.
Results Point of Contact
Name/Title: Local Trial Manager
Organization: Xian-Janssen Pharmaceutical Ltd
Phone: 86-10-5821 8213
Responsible Party: Xian-Janssen Pharmaceutical Ltd.
ClinicalTrials.gov Identifier: NCT00604279     History of Changes
Other Study ID Numbers: CR013150
R092670PSY3008
First Submitted: January 17, 2008
First Posted: January 30, 2008
Results First Submitted: February 21, 2013
Results First Posted: July 10, 2013
Last Update Posted: July 10, 2013