Text Size

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00490971
First received: June 18, 2007
Last updated: October 27, 2012
Last verified: October 2012
History of Changes
Results First Received: April 26, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Bipolar Disorder
Interventions: Drug: Olanzapine
Drug: Paliperidone ER
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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

Reporting Groups
  Description
Paliperidone Extented Release (ER) Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Olanzapine Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Pali/Placebo Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Pali/Pali Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Olan/Olan Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)

Participant Flow for 2 periods

 Period 1:   Acute/Continuation
    Paliperidone Extented Release (ER)     Olanzapine     Pali/Placebo     Pali/Pali     Olan/Olan  
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  
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 2:   Maintenance
    Paliperidone Extented Release (ER)     Olanzapine     Pali/Placebo     Pali/Pali     Olan/Olan  
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  
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.



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
Paliperidone ER Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Olanzapine Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Total Total of all reporting groups

Baseline Measures
    Paliperidone ER     Olanzapine     Total  
Number of Participants  
[units: participants]
 		  614     148     762  
Age  
[units: participants]
 		     
<=18 years     7     3     10  
Between 18 and 65 years     606     145     751  
>=65 years     1     0     1  
Age  
[units: years]
Mean ± Standard Deviation 		  39.7  ± 11.93     39.2  ± 11.49     39.6  ± 11.84  
Gender  
[units: participants]
 		     
Female     310     80     390  
Male     304     68     372  
Region of Enrollment  
[units: 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  
[units: participants]
 		     
18-25     98     25     123  
26-50     378     96     474  
51-65     138     27     165  
>65     0     0     0  
<18     0     0     0  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Recurrence of Any Mood Symptoms (Manic or Depressive) 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. ]
  Show Outcome Measure 1

2.  Secondary:   Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder   [ 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. ]
  Show Outcome Measure 2

3.  Secondary:   Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder   [ 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. ]
  Show Outcome Measure 3

4.  Other Pre-specified:   Young Mania Rating Scale (YMRS): Change From Baseline   [ 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). ]
  Show Outcome Measure 4

5.  Other Pre-specified:   Montgomery-Asberg Depression Rating Scale (MADRS)   [ 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). ]
  Show Outcome Measure 5

6.  Other Pre-specified:   Global Assessment of Functioning (GAF): Change From Baseline   [ 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 6

Measure Type Other Pre-specified
Measure Title Global Assessment of Functioning (GAF): Change From Baseline
Measure 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).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat

Reporting Groups
  Description
Paliperidone ER Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily.
Olanzapine Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily.
Pali/Placebo Maintenance period. Placebo (Paliperidone in the acute and continuation period).
Pali/Pali Maintenance period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily (Paliperidone in the acute and continuation period)
Olan/Olan Maintenance period. Olanzapine Oral tablet, 5 mg/day to 20 mg/day, Once daily (Olanzapine in the acute and continuation period)

Measured Values
    Paliperidone ER     Olanzapine     Pali/Placebo     Pali/Pali     Olan/Olan  
Number of Participants Analyzed  
[units: participants]
 		  575     137     131     135     77  
Global Assessment of Functioning (GAF): Change From Baseline  
[units: Scores on the scale]
Mean ± Standard Deviation 		  19.6  ± 17.38     20.8  ± 18.26     -15.2  ± 20.93     -8.9  ± 17.75     -4.2  ± 13.98  


Statistical Analysis 1 for Global Assessment of Functioning (GAF): Change From Baseline
Groups [1] Pali/Placebo vs. Pali/Pali
Method [2] ANCOVA
P Value [3] 0.010
Mean Difference (Final Values) [4] 5.7
95% Confidence Interval ( 1.40 to 10.09 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)
[2] Other relevant information, such as adjustments or degrees of freedom:
  ANCOVA Model with treatment (Pali/Pali, Pali/Placebo) and country as factors with baseline value as covariate
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



7.  Other Pre-specified:   Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline   [ 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). ]
  Show Outcome Measure 7


  Serious Adverse Events
  Show Serious Adverse Events


  Other Adverse Events
  Show Other Adverse Events


  More Information
  Hide More Information

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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.  


Results Point of Contact:  
Name/Title: Clinical Leader
Organization: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
phone: 609-730-2436


No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Publications automatically indexed to this study:


Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00490971     History of Changes
Other Study ID Numbers: CR010825, R076477BIM3004
Study First Received: June 18, 2007
Results First Received: April 26, 2011
Last Updated: October 27, 2012
Health Authority: United States: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health