Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Paliperidone Palmitate 3 Month Formulation for the Treatment of 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: NCT01529515
Recruitment Status : Completed
First Posted : February 9, 2012
Results First Posted : June 18, 2015
Last Update Posted : May 11, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: PP3M 175 mg eq.
Drug: PP3M 263 mg eq.
Drug: PP3M 350 mg eq.
Drug: PP3M 525 mg eq.
Drug: Placebo (20% Intralipid emulsion)
Enrollment 509
Recruitment Details  
Pre-assignment Details A total of 509 participants were enrolled in to the study and 506 participants were entered the Open-label Transition and received at least one dose of study drug (PP1M). 2 participants were enrolled but not received study drug and 1 participant was screen failure.
Arm/Group Title Open-Label Transition Phase: Paliperidone Palmitate 1-Month Open-Label Maintenance Phase: Paliperidone Palmitate 3-Month Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Hide Arm/Group Description Paliperidone palmitate intramuscular (IM) injection was administered at a dose of 150 milligram equivalents (mg eq) on Day 1, 100 mg eq on Day 8, flexible dose (50, 75, 100, or 150 mg eq) on Day 36 and 64, and on Day 92 same dose as on Day 64. Paliperidone palmitate intramuscular (IM) injection was administered at a dose of 3.5-fold multiple of the PP1M dose received on Day 92 during the Transition Phase. Matching placebo [20 percent (%) Intralipid solution] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase.
Period Title: TRANSITION PHASE
Started 506 0 0 0
Completed 379 0 0 0
Not Completed 127 0 0 0
Reason Not Completed
Adverse Event             16             0             0             0
Death             1             0             0             0
Lack of Efficacy             19             0             0             0
Lost to Follow-up             19             0             0             0
Protocol Violation             4             0             0             0
Withdrawal by Subject             51             0             0             0
Failed Maintenance Phase Criteria             8             0             0             0
Other             9             0             0             0
Period Title: MAINTENANCE PHASE
Started 0 379 0 0
Completed 0 305 0 0
Not Completed 0 74 0 0
Reason Not Completed
Adverse Event             0             10             0             0
Lack of Efficacy             0             9             0             0
Lost to Follow-up             0             5             0             0
Protocol Violation             0             12             0             0
Withdrawal by Subject             0             15             0             0
Failed Randomization Criteria             0             13             0             0
Other             0             10             0             0
Period Title: DOUBLE BLIND PHASE
Started 0 0 145 160
Completed 0 0 122 148
Not Completed 0 0 23 12
Reason Not Completed
Adverse Event             0             0             1             0
Lost to Follow-up             0             0             1             3
Pregnancy             0             0             1             0
Withdrawal by Subject             0             0             10             7
Protocol Violation             0             0             1             0
Other             0             0             9             2
Arm/Group Title Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) Total
Hide Arm/Group Description Matching placebo [20 percent (%) Intralipid solution] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase. Total of all reporting groups
Overall Number of Baseline Participants 145 160 305
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 145 participants 160 participants 305 participants
38.5  (11.16) 37.1  (10.87) 37.8  (11.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 145 participants 160 participants 305 participants
Female
35
  24.1%
42
  26.3%
77
  25.2%
Male
110
  75.9%
118
  73.8%
228
  74.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 145 participants 160 participants 305 participants
Colombia 12 13 25
Malaysia 11 12 23
Mexico 10 8 18
Romania 14 13 27
South Korea 4 2 6
Turkey 5 6 11
Ukraine 63 74 137
United States 26 32 58
1.Primary Outcome
Title Time to Relapse During the Double-Blind Phase
Hide Description Time to relapse defined as the time between participant randomization into the double blind Phase and the first documentation of a relapse event. Median time to relapse was estimated by the Kaplan-Meier method.
Time Frame Approximately Week 60
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during the Double-blind Phase and received at least one dose of Double-blind study agent.
Arm/Group Title Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Hide Arm/Group Description:
Matching placebo [20 percent (%) Intralipid solution] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria.
Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase.
Overall Number of Participants Analyzed 145 160
Median (95% Confidence Interval)
Unit of Measure: Days
395.0 [1] 
(274.0 to NA)
NA [2] 
(NA to NA)
[1]
The NA in the context of the upper limit of a 95% Confidence Interval means "infinity".
[2]
Median time to relapse could not be estimated due to insufficient number of relapses observed in this treatment group.
2.Secondary Outcome
Title Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase
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 item is rated 1 (absent) to 7 (extreme). The total score ranging from 30 to 210. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia.
Time Frame Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study agent. Missing data was imputed using LOCF method. Here "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Hide Arm/Group Description:
Matching placebo [20 percent (%) Intralipid solution] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria.
Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase.
Overall Number of Participants Analyzed 142 159
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline 54.3  (9.20) 54.8  (9.96)
Change at Endpoint (Approximately Week 60) 6.7  (14.40) -0.5  (8.36)
3.Secondary Outcome
Title Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase
Hide Description The CGI-S rating scale is used to rate the severity of a participant's overall clinical condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe).
Time Frame Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study agent. Missing data was imputed using LOCF method. Here "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Hide Arm/Group Description:
Matching placebo [20 percent (%) Intralipid solution] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria.
Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase.
Overall Number of Participants Analyzed 142 159
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline 2.8  (0.65) 2.7  (0.68)
Change at Endpoint (Approximately Week 60) 0.4  (0.87) 0.1  (0.60)
4.Secondary Outcome
Title Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase
Hide Description The PSP scale measures personal and social functioning in the domains of: a) Socially useful activities, b) Personal and social relationships, c) Self-care, and d) Disturbing and aggressive behavior. The results of the assessment were converted to a numerical score which ranges from 1 to 100. A score lying between 71 and 100 indicates a mild degree of dysfunction; scores between 31 and 70 indicate varying degrees of difficulty, and a participant with a score of <=30 had functioning so poor that he or she required intensive supervision.
Time Frame Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study agent. Missing data was imputed using LOCF method. Here "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Hide Arm/Group Description:
Matching placebo [20 percent (%) Intralipid solution] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria.
Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase.
Overall Number of Participants Analyzed 142 157
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Baseline 68.5  (8.93) 68.9  (9.34)
Change at Endpoint (Approximately Week 60) -4.2  (9.70) -0.5  (6.63)
Time Frame Up to Week 92
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Open-Label Phase: PP1M + PP3M Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Hide Arm/Group Description PP1M= Paliperidone Palmitate 1 Month and PP3M= Paliperidone Palmitate 3 Month. Open-Label Transition Phase: Paliperidone palmitate intramuscular (IM) injection was administered at a dose of 150 milligram equivalents (mg eq) on Day 1, 100 mg eq on Day 8, flexible dose (50, 75, 100, or 150 mg eq) on Day 36 and 64, and on Day 92 same dose as on Day 64. Open-Label Maintenance Phase: Paliperidone palmitate intramuscular (IM) injection was administered at a dose of 3.5-fold multiple of the PP1M dose received on Day 92 during the Transition Phase. Matching placebo [20 percent (%) Intralipid solution] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase.
All-Cause Mortality
Open-Label Phase: PP1M + PP3M Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Open-Label Phase: PP1M + PP3M Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/506 (6.52%)   15/145 (10.34%)   4/160 (2.50%) 
Gastrointestinal disorders       
Gastritis Erosive * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Megacolon * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Infections and infestations       
Cellulitis * 1  0/506 (0.00%)  1/145 (0.69%)  0/160 (0.00%) 
Pyelonephritis Chronic * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Investigations       
Transaminases Increased * 1  0/506 (0.00%)  1/145 (0.69%)  0/160 (0.00%) 
Metabolism and nutrition disorders       
Diabetes Mellitus * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Diabetic Ketoacidosis * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Nervous system disorders       
Syncope * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Psychiatric disorders       
Anxiety * 1  1/506 (0.20%)  1/145 (0.69%)  0/160 (0.00%) 
Delusion * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Depression * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Hallucination, Auditory * 1  2/506 (0.40%)  0/145 (0.00%)  0/160 (0.00%) 
Hallucination, Visual * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Psychotic Disorder * 1  9/506 (1.78%)  0/145 (0.00%)  0/160 (0.00%) 
Schizophrenia * 1  12/506 (2.37%)  11/145 (7.59%)  1/160 (0.63%) 
Schizophrenia, Paranoid Type * 1  1/506 (0.20%)  0/145 (0.00%)  1/160 (0.63%) 
Substance-Induced Psychotic Disorder * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Suicidal Ideation * 1  2/506 (0.40%)  1/145 (0.69%)  0/160 (0.00%) 
Suicide Attempt * 1  0/506 (0.00%)  0/145 (0.00%)  2/160 (1.25%) 
Renal and urinary disorders       
Calculus Urinary * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Reproductive system and breast disorders       
Benign Prostatic Hyperplasia * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Chronic Obstructive Pulmonary Disease * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
Vascular disorders       
Venous Thrombosis Limb * 1  1/506 (0.20%)  0/145 (0.00%)  0/160 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Open-Label Phase: PP1M + PP3M Double-Blind Phase: Placebo Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   317/506 (62.65%)   77/145 (53.10%)   98/160 (61.25%) 
Gastrointestinal disorders       
Nausea * 1  11/506 (2.17%)  0/145 (0.00%)  2/160 (1.25%) 
General disorders       
Injection Site Pain * 1  44/506 (8.70%)  0/145 (0.00%)  2/160 (1.25%) 
Fatigue * 1  13/506 (2.57%)  0/145 (0.00%)  2/160 (1.25%) 
Injection Site Swelling * 1  11/506 (2.17%)  0/145 (0.00%)  1/160 (0.63%) 
Irritability * 1  6/506 (1.19%)  3/145 (2.07%)  1/160 (0.63%) 
Infections and infestations       
Nasopharyngitis * 1  14/506 (2.77%)  2/145 (1.38%)  9/160 (5.63%) 
Influenza * 1  5/506 (0.99%)  3/145 (2.07%)  3/160 (1.88%) 
Upper Respiratory Tract Infection * 1  9/506 (1.78%)  3/145 (2.07%)  6/160 (3.75%) 
Urinary Tract Infection * 1  2/506 (0.40%)  2/145 (1.38%)  5/160 (3.13%) 
Investigations       
Weight Decreased * 1  8/506 (1.58%)  11/145 (7.59%)  2/160 (1.25%) 
Weight Increased * 1  51/506 (10.08%)  5/145 (3.45%)  14/160 (8.75%) 
Blood Glucose Increased * 1  0/506 (0.00%)  3/145 (2.07%)  3/160 (1.88%) 
Metabolism and nutrition disorders       
Decreased Appetite * 1  0/506 (0.00%)  3/145 (2.07%)  1/160 (0.63%) 
Hyperglycaemia * 1  0/506 (0.00%)  4/145 (2.76%)  0/160 (0.00%) 
Nervous system disorders       
Headache * 1  33/506 (6.52%)  6/145 (4.14%)  14/160 (8.75%) 
Akathisia * 1  17/506 (3.36%)  1/145 (0.69%)  7/160 (4.38%) 
Somnolence * 1  15/506 (2.96%)  0/145 (0.00%)  1/160 (0.63%) 
Tremor * 1  12/506 (2.37%)  0/145 (0.00%)  2/160 (1.25%) 
Psychiatric disorders       
Anxiety * 1  43/506 (8.50%)  15/145 (10.34%)  13/160 (8.13%) 
Insomnia * 1  50/506 (9.88%)  17/145 (11.72%)  11/160 (6.88%) 
Schizophrenia * 1  4/506 (0.79%)  8/145 (5.52%)  1/160 (0.63%) 
Agitation * 1  8/506 (1.58%)  3/145 (2.07%)  2/160 (1.25%) 
Suicidal Ideation * 1  13/506 (2.57%)  3/145 (2.07%)  0/160 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  3/506 (0.59%)  3/145 (2.07%)  5/160 (3.13%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 15.1
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.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. if requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
Name/Title: Director Clinical Research
Organization: Janssen Research & Development, LLC
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01529515     History of Changes
Other Study ID Numbers: CR100717
R092670PSY3012 ( Other Identifier: Janssen Research & Development, LLC )
2011-004676-11 ( EudraCT Number )
U1111-1135-1969 ( Other Identifier: Universal Trial Number )
First Submitted: February 6, 2012
First Posted: February 9, 2012
Results First Submitted: April 7, 2015
Results First Posted: June 18, 2015
Last Update Posted: May 11, 2016