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Prevention of Relapse With Injectable Paliperidone Palmitate Versus Oral Antipsychotics (PROSIPAL)

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ClinicalTrials.gov Identifier: NCT01081769
Recruitment Status : Completed
First Posted : March 5, 2010
Results First Posted : February 18, 2015
Last Update Posted : February 18, 2015
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Schizophrenia
Interventions Drug: paliperidone palmitate injection
Drug: oral antipsychotics
Enrollment 769
Recruitment Details  
Pre-assignment Details After randomization patients enrolled in a 2-week oral treatment phase and were considered part of the whole Intent-to-Treat population (Whole ITT). Five patients did not receive study medication after randomization and were excluded from the whole ITT. Only responders were considered for continuation in the Core treatment phase (Core ITT).
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter Oral antipsychotics daily treatment according to local label for maximally 24 months
Period Title: Whole Intent-to-Treat
Started 376 388
Completed 352 363
Not Completed 24 25
Reason Not Completed
Missing Responder Assessment             10             12
Stopped; non-responder after 2 weeks             6             6
Deviation; non-responder after 2 weeks             6             7
Responder after 2 weeks, but stopped             2             0
Period Title: CORE Intent-To-Treat
Started 352 363
Completed 272 266
Not Completed 80 97
Reason Not Completed
Adverse Event             14             11
Death             1             1
Lack of Efficacy             2             6
Lost to Follow-up             4             5
Pregnancy             1             0
Withdrawal by Subject             52             60
Noncompliance With Study Drug             0             5
Other             0             1
Ineligibility             3             4
Visit Schedule Issues             1             2
Patient Moved             2             2
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics Total
Hide Arm/Group Description 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter Oral antipsychotics daily treatment according to local label for maximally 24 months Total of all reporting groups
Overall Number of Baseline Participants 376 388 764
Hide Baseline Analysis Population Description
Whole Intent-to-Treat population: All randomized patients who received at least 1 dose of study medication during the screening or treatment phase
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 376 participants 388 participants 764 participants
32.5  (10.73) 32.4  (10) 32.5  (10.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 376 participants 388 participants 764 participants
Female
147
  39.1%
171
  44.1%
318
  41.6%
Male
229
  60.9%
217
  55.9%
446
  58.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 376 participants 388 participants 764 participants
AUSTRIA 0 1 1
BELGIUM 7 5 12
BULGARIA 15 15 30
CROATIA 12 12 24
CZECH REPUBLIC 14 21 35
EGYPT 16 14 30
ESTONIA 2 3 5
FRANCE 4 4 8
GERMANY 3 2 5
HUNGARY 15 16 31
ISRAEL 6 5 11
ITALY 10 11 21
JORDAN 15 11 26
KOREA, REPUBLIC OF KOREA 2 4 6
LITHUANIA 13 14 27
POLAND 11 11 22
ROMANIA 13 14 27
RUSSIAN FEDERATION 90 90 180
SLOVAKIA 13 14 27
SOUTH AFRICA 26 24 50
SPAIN 3 4 7
TAIWAN, PROVINCE OF CHINA 4 5 9
TURKEY 11 9 20
UKRAINE 71 79 150
1.Primary Outcome
Title Time to First Relapse Event
Hide Description Number of days from baseline (day 1 of core phase) to relapse as evaluated according the Csernansky criteria. A patient was considered to have relapsed if they met one or more of the following criteria: (1) psychiatric hospitalization; (2) an increase in the level of psychiatric care and an increase of 25 percent (%) from baseline in the Positive And Negative Syndrome Score (PANSS) total score (or an increase of 10 points if the baseline score was 40 or less); (3) deliberate self-injury; (4) suicidal or homicidal ideation that was clinically significant in the investigator’s judgment; (5) violent behavior resulting in clinically significant injury to another person or property damage; (6) substantial clinical deterioration, defined as a change score of 6 (“much worse”) or 7 (“very much worse”) on the Clinical Global Impressions Scale (CGI-C); and/or (7) the required dose of the antipsychotic exceeds the maximum approved dose.
Time Frame from baseline (Day 1 of core phase) up to maximally 24 months.
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Error)
Unit of Measure: days
616  (10.9) 603  (13.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Oral Antipsychotics
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0191
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With a Relapse Event
Hide Description Number of participants with a relapse event with relapses evaluated according the Csernansky criteria. A patient was considered to have relapsed if they met one or more of the following criteria: (1) psychiatric hospitalization; (2) an increase in the level of psychiatric care and an increase of 25% from baseline in the PANSS total score (or an increase of 10 points if the baseline score was 40 or less); (3) deliberate self-injury; (4) suicidal or homicidal ideation that was clinically significant in the investigator’s judgment; (5) violent behavior resulting in clinically significant injury to another person or property damage; (6) substantial clinical deterioration, defined as a change score of 6 (“much worse”) or 7 (“very much worse”) on the Clinical Global Impressions Scale (CGI-C); and/or (7) the required dose of the antipsychotic exceeds the maximum approved dose.
Time Frame from baseline (Day 1 of core phase) up to maximally 24 months
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Measure Type: Number
Unit of Measure: number of participants
No 300 287
Yes 52 76
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paliperidone Palmitate, Oral Antipsychotics
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0323
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Treatment Responders
Hide Description The proportion of patients achieving a treatment response, defined as a ≥30% decrease (i.e., improvement) in Positive and Negative Syndrome Scale (PANSS) total score from baseline to endpoint. The PANSS is a 30-item scale (Range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate increased severity of schizophrenia symptoms.
Time Frame from baseline (day 1 of core phase) up to maximally 24 months
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
75.6
(70.8 to 79.8)
69.4
(64.5 to 73.9)
4.Secondary Outcome
Title Change From Baseline in PANSS Total Score
Hide Description Change from baseline in the PANSS: The PANSS is a 30-item scale (Range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
Time Frame Baseline, day 8, month 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline score 82.5  (12.03) 81.5  (11.70)
change from baseline at Day 8 -4.8  (5.93) -3.7  (7.04)
change from baseline at Month 1 -9.4  (10.91) -8.8  (10.15)
change from baseline at Month 2 -12.2  (12.19) -12.3  (11.34)
change from baseline at Month 3 -14.5  (11.72) -15.0  (11.15)
change from baseline at Month 4 -16.2  (13.03) -16.8  (12.34)
change from baseline at Month 6 -18.5  (13.67) -18.6  (13.09)
change from baseline at Month 9 -19.5  (14.72) -20.1  (14.35)
change from baseline at Month 12 -21.8  (13.32) -21.2  (14.45)
change from baseline at Month 15 -21.7  (14.56) -21.9  (14.18)
change from baseline at Month 18 -23.5  (13.56) -22.8  (14.41)
change from baseline at Month 21 -24.3  (13.60) -23.7  (14.66)
change from baseline at Month 24 -25.5  (14.42) -24.6  (14.16)
change at Endpoint (LOCF) -16.6  (21.42) -14.1  (21.29)
5.Secondary Outcome
Title Change From Baseline in PANSS Subscale Score
Hide Description Change from baseline in positive symptom, negative symptom and general psychopathology subscales of the PANSS scale. The PANSS scale is designed to assess symptoms of schizophrenia by means of the 30-items. The PANSS scale provides subscores for 3 subscales, that is, the positive symptoms subscale (7 items, range 7-49), the negative symptoms subscale (7 items, range 7-49), and the general psychopathology subscale (16 items, range 16-112). Each item of the scale is to be scored on a scale of 1 (absent) to 7 (extreme). Higher scores indicate higher severity of schizophrenia symptoms.
Time Frame Baseline (day 1 of core phase), day 8, month 12, 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Positive Subscale; Baseline score 18.4  (3.97) 18.3  (4.01)
Positive Subscale; change at Day 8 -1.5  (2.11) -1.3  (2.36)
Positive Subscale; change at Month 12 -6.3  (4.10) -6.2  (4.35)
Positive Subscale; change at Month 24 -6.8  (4.39) -6.7  (4.48)
Positive Subscale; change at Endpoint (LOCF) -4.4  (6.61) -3.8  (6.72)
Negative Subscale; Baseline score 22.6  (4.55) 22.3  (4.58)
Negative Subscale; change at Day 8 -1.0  (1.90) -0.8  (2.10)
Negative Subscale; change at Month 12 -4.8  (4.69) -4.7  (4.80)
Negative Subscale; change at Month 24 -6.2  (5.19) -5.9  (4.74)
Negative Subscale; change at Endpoint (LOCF) -4.1  (6.13) -3.7  (5.79)
General Psychopathology; Baseline score 41.4  (6.73) 40.8  (6.59)
General Psychopathology; change at Day 8 -2.3  (3.58) -1.6  (4.01)
General Psychopathology; change at Month 12 -10.7  (7.19) -10.3  (7.64)
General Psychopathology; change at Month 24 -12.5  (7.63) -12.0  (7.82)
General Psychopathology; change at Endpoint (LOCF) -8.1  (10.96) -6.7  (11.12)
6.Secondary Outcome
Title Change From Baseline in PANSS Marder Factor Scores
Hide Description Change from baseline in schizophrenia symptoms were assessed through the following PANSS factor scores as described by Marder: (1) positive symptoms (range 8-56): sum of delusions, hallucinatory behavior, grandiosity, suspiciousness, stereotyped thinking, somatic concern, unusual thought content, lack of judgment and insight; (2) negative symptoms (range 7-49): sum of blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance; (3) disorganized thoughts (range 7-49): sum of conceptual disorganization, difficulty in abstract thinking, mannerisms and posturing, disorientation, poor attention, disturbance of volition, and preoccupation; (4) uncontrolled hostility/excitement (range 4-28): sum of excitement, hostility, uncooperativeness and poor impulse control; (5) anxiety/depression (range 4-28): sum of anxiety, guilt feelings, tension, and depression. Higher scores indicate higher severity of symptoms
Time Frame Baseline (day 1 of core phase), day 8, month 12 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Positive Symptoms Factor Score; Baseline score 22.9  (4.26) 22.5  (4.39)
Positive Symptoms Factor Score; change at Day 8 -1.5  (2.22) -1.3  (2.50)
Positive Symptoms Factor Score; change at Month 12 -6.9  (4.31) -6.9  (4.76)
Positive Symptoms Factor Score; change at Month 24 -7.6  (4.48) -7.8  (4.95)
Positive Symptoms Factor Score; change at Endpoint -5.0  (6.73) -4.7  (6.80)
Negative Symptoms Factor Score; Baseline score 22.0  (4.65) 21.5  (4.95)
Negative Symptoms Factor Score; change at Day 8 -1.0  (1.93) -0.8  (2.25)
Negative Symptoms Factor Score; change at Month 12 -5.1  (4.73) -4.9  (4.88)
Negative Symptoms Factor Score; change at Month 24 -6.5  (5.16) -6.1  (5.05)
Negative Symptoms Factor Score; change at Endpoint -4.3  (6.26) -3.8  (6.08)
Disorganized Thoughts Factor; Baseline score 19.5  (3.54) 19.4  (3.41)
Disorganized Thoughts Factor; change at Day 8 -1.0  (1.61) -0.6  (2.06)
Disorganized Thoughts Factor; change at Month 12 -4.6  (3.42) -4.6  (3.78)
Disorganized Thoughts Factor; change at Month 24 -5.4  (3.90) -5.4  (3.82)
Disorganized Thoughts Factor; change at Endpoint -3.7  (5.03) -3.2  (5.16)
Uncontrolled Hostility/Excitement; Baseline score 8.4  (2.71) 8.3  (2.64)
Uncontrolled Hostility/Excitement; change at Day 8 -0.7  (1.60) -0.4  (1.47)
Uncontrolled Hostility/Excitement; change Month 12 -2.3  (2.57) -2.1  (2.62)
Uncontrolled Hostility/Excitement; change Month 24 -2.7  (2.77) -2.3  (2.73)
Uncontrolled Hostility/Excitement; change Endpoint -1.5  (3.82) -0.8  (3.87)
Anxiety/Depression Factor; Baseline score 9.7  (2.74) 9.8  (2.85)
Anxiety/Depression Factor; change at Day 8 -0.8  (1.57) -0.6  (1.72)
Anxiety/Depression Factor; change at Month 12 -2.8  (2.67) -2.7  (2.56)
Anxiety/Depression Factor; change at Month 24 -3.3  (2.90) -3.0  (2.78)
Anxiety/Depression Factor; change at Endpoint -2.1  (3.51) -1.8  (3.47)
7.Secondary Outcome
Title Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
Hide Description The Clinical Global Impression Severity (CGI-S) rating scale is a 7 point global clinical 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 scores indicate higher impression of illness severity.
Time Frame Baseline (day 1 of core phase), day 8, month 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline score 3.9  (0.37) 3.8  (0.40)
change from baseline at Day 8 -0.1  (0.38) -0.1  (0.43)
change from baseline at Month 1 -0.3  (0.61) -0.3  (0.61)
change from baseline at Month 2 -0.4  (0.70) -0.5  (0.71)
change from baseline at Month 3 -0.6  (0.69) -0.6  (0.69)
change from baseline at Month 4 -0.7  (0.75) -0.8  (0.71)
change from baseline at Month 6 -0.8  (0.78) -0.8  (0.73)
change from baseline at Month 9 -0.9  (0.80) -0.9  (0.78)
change from baseline at Month 12 -1.0  (0.78) -1.0  (0.80)
change from baseline at Month 15 -0.9  (0.82) -1.0  (0.80)
change from baseline at Month 18 -1.0  (0.80) -1.0  (0.78)
change from baseline at Month 21 -1.0  (0.78) -1.1  (0.82)
change from baseline at Month 24 -1.1  (0.79) -1.1  (0.80)
change from baseline at Endpoint (LOCF) -0.7  (1.14) -0.6  (1.12)
8.Secondary Outcome
Title Clinical Global Impression-Change (CGI-C)
Hide Description The Clinical Global Impression-Change (CGI-C) rating scale is used to rate the change in severity of the patient's illness compared to baseline (day 1 of core phase) on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame Month 24 and endpoint
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Measure Type: Number
Unit of Measure: percentage of participants
Month 24; Very Much Improved 22.9 21.7
Month 24; Much Improved 52.9 47.8
Month 24; Minimally Improved 17.0 20.8
Month 24; No change 6.7 7.7
Month 24; Minimally Worse 0.0 1.0
Month 24; Much Worse 0.4 1.0
Month 24; Very Much Worse 0.0 0.0
Endpoint; Very Much Improved 17.1 14.2
Endpoint; Much Improved 40.6 35.8
Endpoint; Minimally Improved 17.4 21.9
Endpoint; No change 10.6 10.8
Endpoint; Minimally Worse 5.1 6.1
Endpoint; Much Worse 9.1 10.6
Endpoint; Very Much Worse 0.0 0.6
9.Secondary Outcome
Title Changes From Baseline in Personal and Social Performance (PSP) Total Score
Hide Description The Personal and Social Performance (PSP) scale assesses 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. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1, absent to 6, very severe) in each of the 4 domains. Based on 4 domains there will be 1 total score. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.
Time Frame baseline (day 1 of core phase), month 1, 3, 6, 9, 12, 15, 18, 21 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline score 55.3  (11.31) 55.3  (11.07)
change from baseline at Month 1 4.9  (7.78) 4.3  (7.65)
change from baseline at Month 3 7.6  (8.91) 7.7  (9.02)
change from baseline at Month 6 9.9  (10.08) 10.8  (10.32)
change from baseline at Month 9 11.4  (11.28) 11.9  (11.03)
change from baseline at Month 12 12.7  (10.78) 12.3  (11.27)
change from baseline at Month 15 12.9  (11.05) 12.9  (10.82)
change from baseline at Month 18 14.0  (11.44) 13.3  (11.44)
change from baseline at Month 21 14.7  (12.3) 14.0  (11.69)
change from baseline at Month 24 15.2  (12.72) 14.6  (11.72)
change from baseline at Endpoint (LOCF) 9.8  (15.41) 8.7  (14.89)
10.Secondary Outcome
Title Change From Baseline in Short Form-36 Health Survey (SF-36)
Hide Description The Short Form-36 Health Survey (SF-36) is a measure of Participant-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Two summary scale scores are computed based on weighted combinations of the 8 subscale scores: the Physical Component Summary and the Mental Component Summary. Each summary scale score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status.
Time Frame baseline (day 1 of core phase), month 6, 12 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Physical Component, Baseline score 50.3  (8.04) 50.6  (7.83)
Physical Component, change at Month 6 1.2  (6.92) 1.3  (6.52)
Physical Component, change at Month 12 1.6  (7.62) 1.2  (7.08)
Physical Component, change at Month 24 2.2  (8.40) 2.1  (6.74)
Physical Component, change at Endpoint (LOCF) 1.7  (8.52) 1.4  (7.40)
Mental Component, Baseline score 32.1  (12.62) 31.4  (12.92)
Mental Component, change at Month 6 8.2  (11.58) 9.1  (12.43)
Mental Component, change at Month 12 10.5  (11.75) 11.6  (12.77)
Mental Component, change at Month 24 12.0  (13.34) 12.3  (12.83)
Mental Component, change at Endpoint (LOCF) 9.0  (14.99) 8.7  (14.37)
11.Secondary Outcome
Title Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) VAS Score
Hide Description The EQ-5D VAS records the respondent’s self-rated health on a vertical, visual analog scale, with 0 representing the worst imaginable health state and 100 representing the best imaginable health state. The EQ VAS is used as a quantitative measure of health outcome as judged by the individual respondent.
Time Frame baseline (day 1 of core phase), month 6, 12 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline score 57.5  (20.94) 57.6  (20.41)
change from baseline at Month 6 10.6  (17.31) 11.9  (17.00)
change from baseline at Month 12 15.0  (17.38) 15.6  (18.32)
change from baseline at Month 24 17.9  (19.48) 18.6  (17.36)
change from baseline at Endpoint (LOCF) 13.0  (22.87) 11.9  (21.54)
12.Secondary Outcome
Title Change From Baseline in EuroQol 5-Dimensional Questionnaire (EQ-5D) Index Score
Hide Description The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead. A higher score indicates an improvement in health in the Health Status Index.
Time Frame baseline (day 1 of core phase), month 6, 12 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline score 0.80  (0.173) 0.78  (0.181)
change from baseline at Month 6 0.06  (0.181) 0.09  (0.157)
change from baseline at Month 12 0.08  (0.185) 0.11  (0.179)
change from baseline at Month 24 0.10  (0.201) 0.12  (0.161)
change from baseline at Endpoint (LOCF) 0.06  (0.224) 0.08  (0.192)
13.Secondary Outcome
Title Change From Baseline in Subjective Well-Being Under Neuroleptics-Short Form (SWN-S) Total Score
Hide Description The SWN-S is a patient self-rated scale developed to measure the subjective well-being for the previous 7 days of a patient under neuroleptic treatment. The SWN-S consists of 20 items (each item is rated from 1=not at all to 6=very much). The total score ranges from 20 to 120 with higher score indicating greater subjective well-being.
Time Frame baseline (day 1 of core phase), month 6, 12 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline score 76.5  (17.02) 76.7  (17.07)
change from baseline at Month 6 8.4  (14.06) 9.1  (14.40)
change from baseline at Month 12 11.4  (15.81) 11.1  (17.02)
change from baseline at Month 24 13.4  (18.14) 13.1  (15.76)
change from baseline at Endpoint (LOCF) 9.7  (19.17) 8.3  (17.58)
14.Secondary Outcome
Title Change From Baseline in Patient’s Treatment Satisfaction
Hide Description Patient’s satisfaction with medication was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM). The TSQM is divided into 4 subscales (effectiveness, side effects, convenience, and global satisfaction), with the value of each subscale ranging from 0 to 100. Higher scores indicate greater treatment satisfaction.
Time Frame baseline (day 1 of core phase), month 12 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Effectiveness; Baseline score 61.9  (16.97) 59.5  (16.82)
Effectiveness; change at Month 12 6.7  (22.72) 6.6  (21.99)
Effectiveness; change at Month 24 8.5  (21.75) 12.4  (20.69)
Effectiveness; change at Endpoint (LOCF) 3.8  (23.47) 4.5  (25.31)
Side-effects; Baseline score 91.3  (19.74) 87.3  (23.41)
Side-effects; change at Month 12 2.1  (22.71) 2.5  (25.66)
Side-effects; change at Month 24 2.8  (20.93) 3.5  (23.96)
Side-effects; change at Endpoint (LOCF) -1.4  (25.59) 0.7  (28.24)
Convenience; Baseline score 67.1  (16.66) 68.4  (16.45)
Convenience; change at Month 12 8.4  (19.10) 1.0  (17.79)
Convenience; change at Month 24 10.4  (20.49) 4.7  (17.69)
Convenience; change at Endpoint (LOCF) 7.4  (21.24) 0.3  (21.68)
Global Satisfaction; Baseline score 64.0  (18.13) 62.8  (18.31)
Global Satisfaction; change at Month 12 8.2  (18.89) 7.0  (21.18)
Global Satisfaction; change at Month 24 8.6  (21.06) 9.2  (20.39)
Global Satisfaction; change at Endpoint (LOCF) 3.0  (25.01) 1.0  (26.76)
15.Secondary Outcome
Title Change From Baseline in Physician’s Treatment Satisfaction
Hide Description Physician’s treatment satisfaction was assessed using the physician’s treatment satisfaction scale which is designed to rate 4 aspects of treatment (efficacy, safety, mode of administration, and overall satisfaction), each on a scale ranging from 1 (extremely satisfied) to 7 (extremely dissatisfied).
Time Frame baseline (day 1 of core phase), month 12 and 24
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Hide Analysis Population Description
all randomized subjects who responded at the end of the 2-week initial acute oral treatment phase, who also received at least one dose of study medication during the 24-month core treatment phase and provided at least one post-baseline efficacy assessment
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description:
paliperidone palmitate injection with 150 mg equivalent on Day 1 100 mg equivalent on Day 8 75 mg equivalent on Day 38 and flexible dosing with 25 50 75 100 or 150 mg equivalent once monthly thereafter
oral antipsychotics daily treatment according to local label for maximally 24 months
Overall Number of Participants Analyzed 352 363
Mean (Standard Deviation)
Unit of Measure: units on a scale
Efficacy; Baseline score 2.7  (0.79) 2.8  (0.79)
Efficacy; change at Month 12 -0.5  (1.03) -0.4  (0.92)
Efficacy; change at Month 24 -0.6  (1.10) -0.6  (0.98)
Efficacy; change at Endpoint (LOCF) -0.2  (1.46) 0.0  (1.43)
Safety; Baseline score 2.4  (0.80) 2.6  (0.77)
Safety; change at Month 12 -0.4  (0.97) -0.2  (0.90)
Safety; change at Month 24 -0.4  (0.97) -0.3  (1.04)
Safety; change at Endpoint (LOCF) -0.2  (1.19) -0.0  (1.18)
Mode of Administration: Baseline score 2.6  (0.86) 2.6  (0.83)
Mode of Administration: change at Month 12 -0.7  (1.02) -0.0  (0.92)
Mode of Administration: change at Month 24 -0.7  (1.09) -0.1  (0.92)
Mode of Administration: change at Endpoint (LOCF) -0.5  (1.16) 0.0  (1.04)
Overall Satisfaction; Baseline score 2.6  (0.78) 2.7  (0.74)
Overall Satisfaction; change at Month 12 -0.5  (0.95) -0.3  (0.84)
Overall Satisfaction; change at Month 24 -0.6  (1.00) -0.3  (0.86)
Overall Satisfaction; change at Endpoint (LOCF) -0.2  (1.25) 0.1  (1.16)
Time Frame from randomization until maximally month 24
Adverse Event Reporting Description Only patients who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events
 
Arm/Group Title Paliperidone Palmitate Oral Antipsychotics
Hide Arm/Group Description 2 weeks oral paliperidone treatment followed by intramuscular injection with 150 mg paliperidone palmitate equivalent on Day 1 of the core treatment phase, 100 mg equivalent on Day 8, 75 mg equivalent on Day 38 and flexible dosing with 25, 50, 75, 100 or 150 mg equivalent once monthly thereafter Oral antipsychotics daily treatment according to local label for maximally 24 months
All-Cause Mortality
Paliperidone Palmitate Oral Antipsychotics
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Paliperidone Palmitate Oral Antipsychotics
Affected / at Risk (%) Affected / at Risk (%)
Total   42/376 (11.17%)   48/388 (12.37%) 
Cardiac disorders     
Cardiac arrest * 1  1/376 (0.27%)  0/388 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/376 (0.27%)  0/388 (0.00%) 
Haemorrhoids * 1  0/376 (0.00%)  1/388 (0.26%) 
Salivary hypersecretion * 1  0/376 (0.00%)  1/388 (0.26%) 
General disorders     
Sudden death * 1  0/376 (0.00%)  1/388 (0.26%) 
Hepatobiliary disorders     
Cholecystitis chronic * 1  1/376 (0.27%)  0/388 (0.00%) 
Infections and infestations     
Bronchitis * 1  1/376 (0.27%)  0/388 (0.00%) 
Hepatic echinococciasis * 1  0/376 (0.00%)  1/388 (0.26%) 
Pneumonia * 1  0/376 (0.00%)  1/388 (0.26%) 
Sinusitis * 1  1/376 (0.27%)  0/388 (0.00%) 
Injury, poisoning and procedural complications     
Foreign body * 1  1/376 (0.27%)  0/388 (0.00%) 
Multiple injuries * 1  1/376 (0.27%)  0/388 (0.00%) 
Overdose * 1  0/376 (0.00%)  1/388 (0.26%) 
Tibia fracture * 1  0/376 (0.00%)  1/388 (0.26%) 
Investigations     
Alanine aminotransferase increased * 1  1/376 (0.27%)  0/388 (0.00%) 
Musculoskeletal and connective tissue disorders     
Prognathism * 1  0/376 (0.00%)  1/388 (0.26%) 
Nervous system disorders     
Epilepsy * 1  0/376 (0.00%)  1/388 (0.26%) 
Psychiatric disorders     
Acute psychosis * 1  1/376 (0.27%)  0/388 (0.00%) 
Agitation * 1  1/376 (0.27%)  2/388 (0.52%) 
Alcohol abuse * 1  0/376 (0.00%)  2/388 (0.52%) 
Anxiety * 1  2/376 (0.53%)  0/388 (0.00%) 
Psychotic disorder * 1  7/376 (1.86%)  8/388 (2.06%) 
Schizophrenia * 1  21/376 (5.59%)  22/388 (5.67%) 
Schizophrenia, paranoid type * 1  3/376 (0.80%)  4/388 (1.03%) 
Suicide attempt * 1  0/376 (0.00%)  2/388 (0.52%) 
Renal and urinary disorders     
Calculus bladder * 1  1/376 (0.27%)  0/388 (0.00%) 
Reproductive system and breast disorders     
Varicocele * 1  1/376 (0.27%)  0/388 (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%
Paliperidone Palmitate Oral Antipsychotics
Affected / at Risk (%) Affected / at Risk (%)
Total   208/376 (55.32%)   208/388 (53.61%) 
Ear and labyrinth disorders     
Vertigo * 1  8/376 (2.13%)  6/388 (1.55%) 
Gastrointestinal disorders     
Diarrhoea * 1  8/376 (2.13%)  7/388 (1.80%) 
Nausea * 1  12/376 (3.19%)  13/388 (3.35%) 
General disorders     
Asthenia * 1  7/376 (1.86%)  8/388 (2.06%) 
Fatigue * 1  9/376 (2.39%)  7/388 (1.80%) 
Injection site pain * 1  24/376 (6.38%)  0/388 (0.00%) 
Infections and infestations     
Influenza * 1  6/376 (1.60%)  8/388 (2.06%) 
Nasopharyngitis * 1  25/376 (6.65%)  20/388 (5.15%) 
Investigations     
Weight decreased * 1  9/376 (2.39%)  9/388 (2.32%) 
Weight increased * 1  58/376 (15.43%)  65/388 (16.75%) 
Metabolism and nutrition disorders     
Increased appetite * 1  9/376 (2.39%)  12/388 (3.09%) 
Musculoskeletal and connective tissue disorders     
Muscle rigidity * 1  12/376 (3.19%)  8/388 (2.06%) 
Nervous system disorders     
Akathisia * 1  21/376 (5.59%)  22/388 (5.67%) 
Headache * 1  40/376 (10.64%)  34/388 (8.76%) 
Sedation * 1  6/376 (1.60%)  10/388 (2.58%) 
Somnolence * 1  13/376 (3.46%)  22/388 (5.67%) 
Tremor * 1  22/376 (5.85%)  17/388 (4.38%) 
Psychiatric disorders     
Agitation * 1  9/376 (2.39%)  9/388 (2.32%) 
Anxiety * 1  22/376 (5.85%)  23/388 (5.93%) 
Depression * 1  11/376 (2.93%)  9/388 (2.32%) 
Insomnia * 1  42/376 (11.17%)  39/388 (10.05%) 
Schizophrenia * 1  9/376 (2.39%)  15/388 (3.87%) 
Suicidal ideation * 1  20/376 (5.32%)  23/388 (5.93%) 
Reproductive system and breast disorders     
Amenorrhoea * 1  11/376 (2.93%)  7/388 (1.80%) 
*
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 prior to submission for publication or presentation.

No paper that incorporates Confidential Information will be submitted for publication without Sponsor’s prior written consent. If requested in writing, such publication will be withheld for up to an additional 60 calendar days. A publication from the individual Study site data will not be published until the combined results have been published.

Results Point of Contact
Name/Title: EMEA Medical Affairs Director Psychiatry
Organization: Janssen-Cilag Germany
Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT01081769     History of Changes
Obsolete Identifiers: NCT01359293
Other Study ID Numbers: CR015199
R092670SCH3005 ( Other Identifier: Janssen CTMS ID )
2008-002247-16 ( EudraCT Number )
First Submitted: March 4, 2010
First Posted: March 5, 2010
Results First Submitted: November 17, 2014
Results First Posted: February 18, 2015
Last Update Posted: February 18, 2015