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A Study to Evaluate the Effectiveness and Safety of Extended-Release (ER) Paliperidone Compared With Placebo in Delaying the Recurrence of Symptoms in Bipolar I Disorder

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ClinicalTrials.gov Identifier: NCT00490971
Recruitment Status : Completed
First Posted : June 25, 2007
Results First Posted : March 5, 2012
Last Update Posted : April 15, 2015
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 Bipolar Disorder
Interventions Drug: Olanzapine
Drug: Paliperidone ER
Drug: Placebo
Enrollment 768
Recruitment Details  
Pre-assignment Details The double-blind (ie, niether physician nor patient knows the treatment that the patient receives) study has 15-week acute/continuation phase followed by variable-duration maintenance phase (lasting until patient had recurrence or discontinued treatment) to assess effect of paliperidone on maintenance of remission of Bipolar I Disorder
Arm/Group Title Paliperidone Extented Release (ER) Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily. Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily. Maintenance period. Placebo (Paliperidone in the acute and continuation period). Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period) Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Period Title: Acute/Continuation
Started 614 [1] 148 [2] 0 [3] 0 [3] 0 [3]
Completed 308 86 0 [3] 0 [3] 0 [3]
Not Completed 306 62 0 0 0
Reason Not Completed
Adverse Event             62             13             0             0             0
Death             2             0             0             0             0
Lack of Efficacy             106             12             0             0             0
Lost to Follow-up             23             7             0             0             0
Protocol Violation             10             2             0             0             0
Withdrawal by Subject             92             24             0             0             0
Not specified             11             4             0             0             0
[1]
617 participants were assigned to paliperidone, out of which 614 took the study medication.
[2]
149 participants were assigned to paliperidone, out of which 148 took the study medication.
[3]
"0" indicates this group is not relevant to acute and continuation period.
Period Title: Maintenance
Started 0 [1] 0 [1] 147 [2] 149 [3] 83
Completed 0 [1] 0 [1] 96 96 44
Not Completed 0 0 51 53 39
Reason Not Completed
Adverse Event             0             0             4             5             7
Death             0             0             0             2             0
Lost to Follow-up             0             0             5             8             10
Pregnancy             0             0             1             0             0
Protocol Violation             0             0             4             1             1
Withdrawal by Subject             0             0             26             28             18
Not specified             0             0             11             9             3
[1]
"0" indicates this group is not relevant to maintenance period.
[2]
148 participants were assigned to pali/placebo, out of which 147 took the study medication.
[3]
152 participants were assigned to pali/pali, out of which 149 took the study medication.
Arm/Group Title Paliperidone ER Olanzapine Total
Hide Arm/Group Description Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily. Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily. Total of all reporting groups
Overall Number of Baseline Participants 614 148 762
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 614 participants 148 participants 762 participants
<=18 years
7
   1.1%
3
   2.0%
10
   1.3%
Between 18 and 65 years
606
  98.7%
145
  98.0%
751
  98.6%
>=65 years
1
   0.2%
0
   0.0%
1
   0.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 614 participants 148 participants 762 participants
39.7  (11.93) 39.2  (11.49) 39.6  (11.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 614 participants 148 participants 762 participants
Female
310
  50.5%
80
  54.1%
390
  51.2%
Male
304
  49.5%
68
  45.9%
372
  48.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 148 participants 762 participants
Asia 162 36 198
Eastern Europe 129 31 160
European Union 71 19 90
North America 177 41 218
Other 75 21 96
India 69 14 83
Malaysia 7 2 9
China 86 20 106
Russian Federation 51 11 62
Serbia 32 8 40
Ukraine 46 12 58
Bulgaria 27 6 33
Germany 6 3 9
Poland 16 5 21
Romania 22 5 27
Costa Rica 12 4 16
Morocco 6 2 8
Panama 3 1 4
South Africa 26 6 32
Tunisia 10 4 14
Turkey 18 4 22
United States 177 41 218
AgeCategorical  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 614 participants 148 participants 762 participants
18-25 98 25 123
26-50 378 96 474
51-65 138 27 165
>65 0 0 0
<18 0 0 0
1.Primary Outcome
Title Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder
Hide Description Time to first recurrence of any mood symptoms (ie, manic or depressive) associated with bipolar I disorder during the maintenance phase, after maintaining clinical stability during continued treatment with paliperidone ER over a period of 15 weeks. The time period was from occurrence of acute manic or mixed episode to Week 15. This outcome was measured using combination of various scales, hospitalization for any mood symptoms, use of any medicines for an mood episode and clinical events suggestive of recurrent mood episode associated with bipolar I disorder.
Time Frame Date of randomization into the maintenance phase until the first occurrence of recurrence of any symptoms or discontinuation from the study, assessed over a period of 41 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat analysis set (ITT) in maintenance (MA) phase, which included participants who entered the MA phase and took at least 1 dose of study medication.
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description:
Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Overall Number of Participants Analyzed 0 0 144 146 82
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Days
25% Quantile of Time to Recurrence
85.0
(72.0 to 141.0)
140.0
(72.0 to 274.0)
541 [1] 
(386.0 to NA)
Median Time to Recurrence
283.0
(203.0 to 531.0)
558.0
(401.0 to 804.0)
NA [2] 
(NA to NA)
[1]
There were 23% of the subjects in Olan/Olan treatment group who reported recurrence. Hence 25% quantile of time to recurrence was not observed
[2]
There were 23% of the subjects in Olan/Olan treatment group who reported recurrence. Hence median time to recurrence was not observed
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pali/Placebo
Comments Null hypothesis: there is no difference between Pali/Pali and Pali/Placebo in the time to recurrence of any mood symptoms related to bipolar I disorder. An interim analysis was performed when approximately 85% of the required number of recurrences were reported in Pali/Pali and Pali/Placebo treatment groups. A flexible group-sequential approach was adopted. The general family of alpha spending function based on the rho-family with rho=2.5 at overall type I error of 0.025 (1-sided) was employed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments The two treatment groups were compared using a weighted z-statistic based on rho-family of alpha spending function at information fraction of 85.0% at interim analysis analysis (rho=2.5) at 0.025 (1-sided) level. One-sided alpha at final was 0.0195.
Method Weighted Z- test
Comments [Not Specified]
2.Secondary Outcome
Title Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder
Hide Description This was the key secondary efficacy end-point. Pali/Pali and Pali/Placebo were compared with each other with respect to time to recurrence of manic symptoms. The criterias used for this analysis were similar to criterias used for primary analysis.
Time Frame Date of randomization into the maintenance phase until the first occurrence of recurrence of manic symptoms or discontinuation from the study, assessed over a period of 41 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat analysis set in MA phase, which included participants who entered the MA phase and took at least 1 dose of study medication.
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description:
Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Overall Number of Participants Analyzed 0 0 144 146 82
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Days
25% Quantile of Time to Recurrence
194.0
(125.0 to 283.0)
498.0
(294.0 to 813.0)
NA [1] 
(595.0 to NA)
Median Time to Recurrence
550.0
(419.0 to 878)
NA [2] 
(813 to NA)
NA [3] 
(NA to NA)
[1]
There were 11% of the subjects in the Olan/Olan group who reported recurrence of manic symptoms. Hence 25% quartile of time to recurrence was not observed.
[2]
There were 21% of the subjects in the Pali/Pali group who reported recurrence of manic symptoms. Hence median time to recurrence was not observed.
[3]
There were 11% of the subjects in the Olan/Olan group who reported recurrence of manic symptoms. Hence median time to recurrence was not observed.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pali/Placebo
Comments At the time of interim analysis of the primary efficacy endpoint, the proportion of recurrence of manic symptoms was 81.9% of the number of recurrence of manic symptoms at final analysis. A flexible group-sequential approach was adopted. The general family of alpha spending function based on the rho-family with rho=2.5 at overall type I error of 0.025 (1-sided) was employed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The two treatment groups were compared using a weighted z-statistic based on rho-family of alpha spending function at information fraction of 81.9% at interim analysis analysis (rho=2.5) at 0.025 (1-sided) level. One-sided alpha at final was 0.0198.
Method Weighted z-test
Comments [Not Specified]
3.Secondary Outcome
Title Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder
Hide Description Pali/Pali and Pali/Placebo were compared with each other with respect to time to recurrence of depressive symptoms. The criterias used for this analysis were similar to criterias used for primary analysis.
Time Frame Date of randomization into the maintenance phase until the first occurrence of recurrence of depressive symptoms or discontinuation from the study, assessed over a period of 41 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat analysis set in MA period, which included participants who entered the maintenance phase and took at least 1 dose of study medication.
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description:
Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Overall Number of Participants Analyzed 0 0 144 146 82
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Days
503.0 [1] 
(203.0 to NA)
448.0
(170.0 to 750.0)
NA [2] 
(651.0 to NA)
[1]
There were 18% of the participants in the Pali/Placebo group who reported recurrence of depressive symptoms.
[2]
There were 12% of the participants in the Olan/Olan group who reported recurrence of depressive symptoms. Hence the 25% quartile of the time to recurrence of depressive symptoms was not observed.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pali/Placebo, Pali/Pali
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Cox proportional hazards regression was performed with treatment (Pali/Placebo, Pali/Pali) as a factor. The 2 treatment groups were compared by means of a hazard ratio (Pali/Placebo: Pali/Pali)
Method Regression, Cox
Comments The percent of participants who reported recurrence of depressive symptoms was: 18% Pali/Placebo, 24% Pali/Pali.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.53 to 1.46
Estimation Comments Hazard ratio was estimated with Pali/Placebo in the numerator and Pali/Pali in the denominator
4.Other Pre-specified Outcome
Title Young Mania Rating Scale (YMRS): Change From Baseline
Hide Description This is method by which condition of patient suffering with mania is checked. In this scale patient's condition is assessed using 11 items. A severity rating is assigned to each of 11 items based on the how subject feels of his or her condition and the physicians observation of patients behavior. The range of the scale is 0 to 60. A higher score indicates a more severe condition. Change from baseline (Day 105) in the double‑blind maintenance phase to the last postbaseline assessment.
Time Frame From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description:
Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Overall Number of Participants Analyzed 602 145 143 144 81
Mean (Standard Deviation)
Unit of Measure: Scores on the scale
-19.2  (11.23) -19.3  (10.25) 9.0  (11.78) 4.2  (9.33) 1.3  (6.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pali/Placebo, Pali/Pali
Comments Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment group (Pali/Pali, Pali/Placebo) and country as factors with baseline value as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.5
Confidence Interval (2-Sided) 95%
-6.92 to -1.98
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Montgomery-Asberg Depression Rating Scale (MADRS)
Hide Description The MADRS consists of 10 items covering all the important complaints which patient with depression have (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Item is scored from 0 (normal) to 6 (severe). Total score (0 to 60) is calculated by adding the scores of all 10 items. A higher score represents a more severe condition. Negative Change in Score Indicates Improvement.
Time Frame From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description:
Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Overall Number of Participants Analyzed 597 144 143 144 81
Mean (Standard Deviation)
Unit of Measure: Scores on the scale
-2.7  (8.21) -2.7  (7.82) 6.0  (9.16) 6.1  (10.10) 2.5  (7.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pali/Placebo, Pali/Pali
Comments Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.763
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA Model with treatment (Pali/Pali, Pali/Placebo) and country as factors with baseline value as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-1.87 to 2.55
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Global Assessment of Functioning (GAF): Change From Baseline
Hide Description This scale is used when the clinical progress of a subject needs to be assessed in global terms, using a single measure. The GAF scale is rated with respect to psychological, social, and occupational functioning at the time of the assessment only. A higher score indicates a better functioning, with an overall range from 1 to 100. Positive Change in Score Indicates Improvement.
Time Frame From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description:
Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Overall Number of Participants Analyzed 575 137 131 135 77
Mean (Standard Deviation)
Unit of Measure: Scores on the scale
19.6  (17.38) 20.8  (18.26) -15.2  (20.93) -8.9  (17.75) -4.2  (13.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pali/Placebo, Pali/Pali
Comments Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA Model with treatment (Pali/Pali, Pali/Placebo) and country as factors with baseline value as covariate
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.7
Confidence Interval (2-Sided) 95%
1.40 to 10.09
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline
Hide Description The CGI-BP-S rating scale is used to rate the severity of bipolar disorder, including both depressed and manic components, on a 7-point scale ranging from 1 (not ill) to 7 (very severely ill). This scale permits a global evaluation of the subject’s bipolar condition at a given time. Negative Change in Score Indicates Improvement.
Time Frame From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description:
Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
Overall Number of Participants Analyzed 601 145 143 144 81
Median (Full Range)
Unit of Measure: Scores on the scale
-2
(-6 to 2)
-3
(-5 to 2)
2
(-1 to 6)
0
(-2 to 5)
0
(-1 to 4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pali/Placebo, Pali/Pali
Comments Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA Model on ranks with treatment (Pali/Pali, Pali/Placebo) and country as factors with baseline value as covariate
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Hide Arm/Group Description Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily. Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily. Maintenance period. Placebo (Paliperidone in the acute and continuation period). Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period) Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)
All-Cause Mortality
Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   42/614 (6.84%)   10/148 (6.76%)   33/147 (22.45%)   16/149 (10.74%)   8/83 (9.64%) 
Cardiac disorders           
Myocardial infarction * 1  2/614 (0.33%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Eye disorders           
Vision blurred * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Gastrointestinal disorders           
Gastritis * 1  0/614 (0.00%)  1/148 (0.68%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Pancreatitis * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  1/83 (1.20%) 
General disorders           
Death * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Infections and infestations           
Abdominal infection * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Hepatitis viral * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Pneumonia * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Sinusitis * 1  0/614 (0.00%)  1/148 (0.68%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Injury, poisoning and procedural complications           
Chest injury * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  1/83 (1.20%) 
Head injury * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  1/83 (1.20%) 
Multiple fractures * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Post procedural complication * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Investigations           
Blood potassium decreased * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  1/83 (1.20%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Breast cancer stage III * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Nervous system disorders           
Akathisia * 1  2/614 (0.33%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Extrapyramidal disorder * 1  2/614 (0.33%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Hypoxic encephalopathy * 1  0/614 (0.00%)  0/148 (0.00%)  1/147 (0.68%)  0/149 (0.00%)  0/83 (0.00%) 
Neuroleptic malignant syndrome * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Psychomotor hyperactivity * 1  2/614 (0.33%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Psychiatric disorders           
Agitation * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Alcohol abuse * 1  2/614 (0.33%)  1/148 (0.68%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Anger * 1  0/614 (0.00%)  0/148 (0.00%)  1/147 (0.68%)  0/149 (0.00%)  0/83 (0.00%) 
Anxiety * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Bipolar I disorder * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Catatonia * 1  0/614 (0.00%)  1/148 (0.68%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Completed suicide * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Depression * 1  4/614 (0.65%)  1/148 (0.68%)  8/147 (5.44%)  4/149 (2.68%)  1/83 (1.20%) 
Depressive symptom * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Hypomania * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Insomnia * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Major depression * 1  0/614 (0.00%)  0/148 (0.00%)  1/147 (0.68%)  1/149 (0.67%)  0/83 (0.00%) 
Mania * 1  10/614 (1.63%)  6/148 (4.05%)  22/147 (14.97%)  3/149 (2.01%)  4/83 (4.82%) 
Pressure of speech * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Psychotic disorder * 1  0/614 (0.00%)  1/148 (0.68%)  1/147 (0.68%)  0/149 (0.00%)  0/83 (0.00%) 
Self-injurious ideation * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Suicidal behaviour * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Suicidal ideation * 1  6/614 (0.98%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Suicide attempt * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Tachyphrenia * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Skin and subcutaneous tissue disorders           
Leukoplakia * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Surgical and medical procedures           
Breast operation * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Mastectomy * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Nasal operation * 1  0/614 (0.00%)  0/148 (0.00%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Sinus operation * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Vascular disorders           
Hypertension * 1  2/614 (0.33%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
Orthostatic hypotension * 1  1/614 (0.16%)  0/148 (0.00%)  0/147 (0.00%)  0/149 (0.00%)  0/83 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Paliperidone ER Olanzapine Pali/Placebo Pali/Pali Olan/Olan
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   351/614 (57.17%)   79/148 (53.38%)   38/147 (25.85%)   38/149 (25.50%)   26/83 (31.33%) 
Gastrointestinal disorders           
Dry mouth * 1  28/614 (4.56%)  14/148 (9.46%)  2/147 (1.36%)  1/149 (0.67%)  1/83 (1.20%) 
Nausea * 1  33/614 (5.37%)  2/148 (1.35%)  2/147 (1.36%)  1/149 (0.67%)  0/83 (0.00%) 
Investigations           
Weight decreased * 1  7/614 (1.14%)  0/148 (0.00%)  9/147 (6.12%)  4/149 (2.68%)  1/83 (1.20%) 
Weight increased * 1  51/614 (8.31%)  18/148 (12.16%)  10/147 (6.80%)  12/149 (8.05%)  7/83 (8.43%) 
Metabolism and nutrition disorders           
Increased appetite * 1  23/614 (3.75%)  13/148 (8.78%)  0/147 (0.00%)  1/149 (0.67%)  0/83 (0.00%) 
Nervous system disorders           
Akathisia * 1  83/614 (13.52%)  11/148 (7.43%)  1/147 (0.68%)  1/149 (0.67%)  2/83 (2.41%) 
Dizziness * 1  41/614 (6.68%)  4/148 (2.70%)  1/147 (0.68%)  4/149 (2.68%)  0/83 (0.00%) 
Extrapyramidal disorder * 1  54/614 (8.79%)  4/148 (2.70%)  1/147 (0.68%)  2/149 (1.34%)  1/83 (1.20%) 
Headache * 1  78/614 (12.70%)  14/148 (9.46%)  7/147 (4.76%)  4/149 (2.68%)  7/83 (8.43%) 
Sedation * 1  38/614 (6.19%)  25/148 (16.89%)  0/147 (0.00%)  0/149 (0.00%)  2/83 (2.41%) 
Somnolence * 1  76/614 (12.38%)  23/148 (15.54%)  0/147 (0.00%)  5/149 (3.36%)  1/83 (1.20%) 
Tremor * 1  34/614 (5.54%)  4/148 (2.70%)  0/147 (0.00%)  1/149 (0.67%)  3/83 (3.61%) 
Psychiatric disorders           
Insomnia * 1  83/614 (13.52%)  15/148 (10.14%)  14/147 (9.52%)  13/149 (8.72%)  7/83 (8.43%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, 12.1
The study employed a randomized withdrawal design, and as such, was enriched for responders to the study drug. Thus, the long-term efficacy demonstrated cannot be extrapolated to a population of patients without prior exposure to paliperidone ER.
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
Name/Title: Clinical Leader
Organization: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Phone: 609-730-2436
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00490971     History of Changes
Other Study ID Numbers: CR010825
R076477BIM3004 ( Other Identifier: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. )
First Submitted: June 18, 2007
First Posted: June 25, 2007
Results First Submitted: April 26, 2011
Results First Posted: March 5, 2012
Last Update Posted: April 15, 2015