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Comparison of Paliperidone Palmitate and RISPERDAL CONSTA in Patients With Schizophrenia

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ClinicalTrials.gov Identifier: NCT00589914
Recruitment Status : Completed
First Posted : January 10, 2008
Results First Posted : October 4, 2011
Last Update Posted : June 24, 2014
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: RISPERDAL CONSTA
Drug: Paliperidone palmitate
Enrollment 1221
Recruitment Details This is a 13 week double-blind study to assess safety and efficacy of flexible dose of Paliperidone Palmitate (50, 100 or 150 mg equivalent) in patients aged 18 years or older with schizophrenia.
Pre-assignment Details In this study 1221 patients were enrolled of which 1220 patients were randomized as 1 patient was enrolled twice. Only the first patient number was included in the all randomized patients, safety, and intent to treat analysis sets. Out of 1220 patients 1214 patients received at least 1 dose of study medication.
Arm/Group Title R092670 RISPERDAL CONSTA
Hide Arm/Group Description Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64). Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).
Period Title: Overall Study
Started 606 608
Completed 456 471
Not Completed 150 137
Reason Not Completed
Adverse Event             19             10
Death             2             0
Lack of Efficacy             40             43
Lost to Follow-up             11             18
Pregnancy             1             0
Withdrawal by Subject             55             49
Other             22             17
Arm/Group Title R092670 RISPERDAL CONSTA Total
Hide Arm/Group Description Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64). Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78). Total of all reporting groups
Overall Number of Baseline Participants 606 608 1214
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 606 participants 608 participants 1214 participants
<=18 years
3
   0.5%
2
   0.3%
5
   0.4%
Between 18 and 65 years
596
  98.3%
599
  98.5%
1195
  98.4%
>=65 years
7
   1.2%
7
   1.2%
14
   1.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 606 participants 608 participants 1214 participants
39  (12.13) 38.7  (11.83) 38.9  (11.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 606 participants 608 participants 1214 participants
Female
245
  40.4%
268
  44.1%
513
  42.3%
Male
361
  59.6%
340
  55.9%
701
  57.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 606 participants 608 participants 1214 participants
Austria 3 3 6
Bulgaria 15 14 29
Czech Republic 50 48 98
Estonia 32 34 66
France 7 3 10
Germany 4 4 8
Hungary 31 34 65
India 31 31 62
Lithuania 17 20 37
Poland 24 20 44
Russia 159 159 318
Spain 17 17 34
Ukraine 84 84 168
United States of America 132 137 269
AgeCategorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 606 participants 608 participants 1214 participants
18-25 years 103 92 195
26-50 years 381 397 778
51-65 years 115 113 228
>65 years 7 6 13
<18 years 0 0 0
1.Primary Outcome
Title Change in the Positive and Negative Syndrome Scale (PANSS) Total Score for Schizophrenia
Hide Description The PANSS scale is used to assess the neuropsychiatric symptoms of schizophrenia. The 30-item PANSS scale 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 item rated on a scale of 1 (absent) to 7 (extreme).
Time Frame Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The per-protocol analysis set of patients included those randomized to treatment after IEC/ IRB approval of protocol Amendment INT-4 with both a baseline measurement and at least 1 postrandomization measurement on the primary efficacy variable, a minimum exposure of 36 days to the double-blind treatment regimen, and no major protocol violations.
Arm/Group Title R092670 RISPERDAL CONSTA
Hide Arm/Group Description:
Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).
Overall Number of Participants Analyzed 389 376
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-18.6  (15.45) -17.9  (14.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection R092670, RISPERDAL CONSTA
Comments Null hypothesis: Difference between groups (RISPERDAL CONSTA minus paliperidone palmitate) for the mean change from baseline to endpoint in PANSS total score (LOCF) was less than or equal to -5 (prespecified non-inferiority margin). Sample size: SD of 20 for the change in PANSS total score, a true difference between treatment groups of 0.1 in favor of RISPERDAL CONSTA, 2-sided significance level of 5%, and 80% power. A sample size reestimation was performed when 60% of the data was available.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority margin was 5 points in the change in PANSS total score i.e., lower limit of the 95% CI for difference between groups (RISPERDAL CONSTA minus paliperidone palmitate) had to be greater than -5 to demonstrate non-inferiority.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments No p-value to report.
Method ANCOVA
Comments ANCOVA model with factors treatment, country and baseline score. Weighted approach used to account for interim analysis for sample size re-estimation.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.62 to 2.38
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.02
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Change From Baseline for the CGI-S Score
Hide Description The CGI-S rating scale is used to rate the severity of a patient’s psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). This scale permits a global evaluation of the patient’s condition at a given time. A qualified rater administered the CGI-S.
Time Frame Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)]
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis set of patients included those randomized to treatment after IEC/IRB approval of protocol Amendment INT-4 who received at least 1 injection of double-blind study drug and had at least 1 efficacy measurement during the double-blind treatment period.
Arm/Group Title R092670 RISPERDAL CONSTA
Hide Arm/Group Description:
Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).
Overall Number of Participants Analyzed 453 460
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-0.9  (0.97) -0.9  (0.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection R092670, RISPERDAL CONSTA
Comments The change from baseline was analyzed using an ANCOVA model with factors for treatment and country and baseline score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments No P-values reported.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.07 to 0.17
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.06
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The Change From Baseline in the PSP Score
Hide Description The PSP scale is used to assess the degree of dysfunction a patient exhibits over a 7-day period within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The results of the assessment are converted to a numeric score. A score between 71 and 100 indicates a mild degree of difficulty; a score between 31 and 70 indicates a moderate degree of dysfunction, and a patient with a score of 30 or less has functioning so poor he or she requires intensive supervision.
Time Frame Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis set of patients included those randomized to treatment after IEC/IRB approval of protocol Amendment INT-4 who received at least 1 injection of double-blind study drug and had at least 1 efficacy measurement during the double-blind treatment period.
Arm/Group Title R092670 RISPERDAL CONSTA
Hide Arm/Group Description:
Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64).
Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).
Overall Number of Participants Analyzed 448 452
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
8.5  (11.82) 8.8  (11.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection R092670, RISPERDAL CONSTA
Comments The change from baseline was analyzed using an ANCOVA model with factors for treatment and country and baseline score as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments No P-values reported.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.22 to 1.69
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.74
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title R092670 RISPERDAL CONSTA
Hide Arm/Group Description Double-blind period. Flexible dose of 50, 100 or 150 mg equivalent administered by i.m. injection every 4 weeks up to Week 9 (Day 64). Double-blind period. Flexible dose of 25, 37.5 or 50 mg administered by i.m. injection every 2 weeks up to Week 11 (Day 78).
All-Cause Mortality
R092670 RISPERDAL CONSTA
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
R092670 RISPERDAL CONSTA
Affected / at Risk (%) Affected / at Risk (%)
Total   41/606 (6.77%)   29/608 (4.77%) 
Gastrointestinal disorders     
Constipation * 1  0/606 (0.00%)  1/608 (0.16%) 
Volvulus of small bowel * 1  0/606 (0.00%)  1/608 (0.16%) 
General disorders     
Death * 1  1/606 (0.17%)  0/608 (0.00%) 
Infections and infestations     
Malaria * 1  0/606 (0.00%)  1/608 (0.16%) 
Urinary tract infection * 1  0/606 (0.00%)  1/608 (0.16%) 
Metabolism and nutrition disorders     
Hyperglycaemia * 1  0/606 (0.00%)  1/608 (0.16%) 
Nervous system disorders     
Syncope * 1  0/606 (0.00%)  1/608 (0.16%) 
Psychiatric disorders     
Agitation * 1  2/606 (0.33%)  2/608 (0.33%) 
Alcohol abuse * 1  0/606 (0.00%)  1/608 (0.16%) 
Anxiety * 1  2/606 (0.33%)  0/608 (0.00%) 
Completed suicide * 1  1/606 (0.17%)  0/608 (0.00%) 
Delirium * 1  0/606 (0.00%)  1/608 (0.16%) 
Delusion * 1  1/606 (0.17%)  0/608 (0.00%) 
Depressive symptom * 1  1/606 (0.17%)  0/608 (0.00%) 
Hallucination * 1  1/606 (0.17%)  0/608 (0.00%) 
Hallucination, auditory * 1  1/606 (0.17%)  0/608 (0.00%) 
Hallucination, visual * 1  1/606 (0.17%)  0/608 (0.00%) 
Paranoia * 1  3/606 (0.50%)  1/608 (0.16%) 
Psychotic disorder * 1  13/606 (2.15%)  7/608 (1.15%) 
Schizophrenia * 1  15/606 (2.48%)  13/608 (2.14%) 
Schizophrenia, paranoid type * 1  1/606 (0.17%)  0/608 (0.00%) 
Suicidal ideation * 1  3/606 (0.50%)  0/608 (0.00%) 
Suicide attempt * 1  0/606 (0.00%)  1/608 (0.16%) 
Tension * 1  1/606 (0.17%)  0/608 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism * 1  0/606 (0.00%)  1/608 (0.16%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MEDDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
R092670 RISPERDAL CONSTA
Affected / at Risk (%) Affected / at Risk (%)
Total   147/606 (24.26%)   108/608 (17.76%) 
General disorders     
Injection site pain * 1  31/606 (5.12%)  5/608 (0.82%) 
Nervous system disorders     
Headache * 1  43/606 (7.10%)  44/608 (7.24%) 
Somnolence * 1  34/606 (5.61%)  24/608 (3.95%) 
Psychiatric disorders     
Insomnia * 1  57/606 (9.41%)  41/608 (6.74%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MEDDRA 12.0
Of 1221 patients randomized, one patient was enrolled twice and assigned 2 patient numbers. Only the first patient number is included in the results reported for 1220 randomized patients.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Leader Psychiatry
Organization: Johnson & Johnson Pharmaceutical Research & Development LLC
Phone: 1 609 730-2324
Layout table for additonal information
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00589914     History of Changes
Other Study ID Numbers: CR012289
R092670PSY3006 ( Other Identifier: Unique Protocol Number )
First Submitted: December 21, 2007
First Posted: January 10, 2008
Results First Submitted: August 30, 2011
Results First Posted: October 4, 2011
Last Update Posted: June 24, 2014