Trial Outcomes & Findings for Effectiveness and Safety of 3 Fixed Doses (25 mg eq., 100 mg eq., and 150 mg eq.) of Paliperidone Palmitate in Patients With Schizophrenia (NCT NCT00590577)
NCT ID: NCT00590577
Last Updated: 2014-06-04
Results Overview
The PANSS measures the severity of psychotic symptoms of schizophrenia. Scores range from 30 to 210, where 30=best and 210=worst. The change in PANSS total score for all eligible subjects was measured from the beginning of the study to Week 13 (i.e., the end of the double-blind treatment period) or, if the subject left the study early, from the beginning of the study to the last assessment after baseline.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
652 participants
Primary outcome timeframe
Baseline to 13 weeks or the last post-baseline assessment
Results posted on
2014-06-04
Participant Flow
The recruitment period was 8 March 2007 (first patient enrolled) to 24 March 2008 (last patient left the study). The study was performed in medical clinics located around the world.
Before assignment to treatment groups, patients stopped taking disallowed medications. At the same time, patients who had not previously taken paliperidone extended release (ER) or risperidone or had previously taken it but were not currently taking another antipsychotic took paliperidone ER 6 mg/day for 4 to 6 days to assess tolerance to the drug.
Participant milestones
| Measure |
Paliperidone Palmitate 25 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
160
|
165
|
163
|
164
|
|
Overall Study
COMPLETED
|
83
|
89
|
90
|
71
|
|
Overall Study
NOT COMPLETED
|
77
|
76
|
73
|
93
|
Reasons for withdrawal
| Measure |
Paliperidone Palmitate 25 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
|---|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
31
|
28
|
23
|
45
|
|
Overall Study
Withdrawal by Subject
|
23
|
28
|
30
|
26
|
|
Overall Study
Adverse Event
|
10
|
10
|
13
|
11
|
|
Overall Study
Lost to Follow-up
|
12
|
6
|
6
|
9
|
|
Overall Study
Pregnancy
|
0
|
1
|
0
|
0
|
|
Overall Study
Various reasons
|
1
|
3
|
1
|
2
|
Baseline Characteristics
Effectiveness and Safety of 3 Fixed Doses (25 mg eq., 100 mg eq., and 150 mg eq.) of Paliperidone Palmitate in Patients With Schizophrenia
Baseline characteristics by cohort
| Measure |
Paliperidone Palmitate 25 mg eq.
n=160 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
n=165 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
n=163 Participants
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
n=164 Participants
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Total
n=652 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
160 Participants
n=5 Participants
|
163 Participants
n=7 Participants
|
160 Participants
n=5 Participants
|
163 Participants
n=4 Participants
|
646 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Age, Continuous
|
39.2 years
STANDARD_DEVIATION 10.33 • n=5 Participants
|
38.7 years
STANDARD_DEVIATION 10.27 • n=7 Participants
|
39.4 years
STANDARD_DEVIATION 10.69 • n=5 Participants
|
39.9 years
STANDARD_DEVIATION 10.96 • n=4 Participants
|
39.3 years
STANDARD_DEVIATION 10.55 • n=21 Participants
|
|
Sex: Female, Male
Female
|
44 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
212 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
116 Participants
n=5 Participants
|
110 Participants
n=7 Participants
|
105 Participants
n=5 Participants
|
109 Participants
n=4 Participants
|
440 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
78 participants
n=5 Participants
|
82 participants
n=7 Participants
|
85 participants
n=5 Participants
|
84 participants
n=4 Participants
|
329 participants
n=21 Participants
|
|
Region of Enrollment
Russian Federation
|
32 participants
n=5 Participants
|
33 participants
n=7 Participants
|
33 participants
n=5 Participants
|
32 participants
n=4 Participants
|
130 participants
n=21 Participants
|
|
Region of Enrollment
Ukraine
|
13 participants
n=5 Participants
|
14 participants
n=7 Participants
|
13 participants
n=5 Participants
|
13 participants
n=4 Participants
|
53 participants
n=21 Participants
|
|
Region of Enrollment
Romania
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
8 participants
n=5 Participants
|
10 participants
n=4 Participants
|
39 participants
n=21 Participants
|
|
Region of Enrollment
Taiwan
|
10 participants
n=5 Participants
|
10 participants
n=7 Participants
|
9 participants
n=5 Participants
|
10 participants
n=4 Participants
|
39 participants
n=21 Participants
|
|
Region of Enrollment
Malaysia
|
7 participants
n=5 Participants
|
8 participants
n=7 Participants
|
7 participants
n=5 Participants
|
7 participants
n=4 Participants
|
29 participants
n=21 Participants
|
|
Region of Enrollment
Korea, Republic of
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
6 participants
n=5 Participants
|
6 participants
n=4 Participants
|
24 participants
n=21 Participants
|
|
Region of Enrollment
Serbia
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
9 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline to 13 weeks or the last post-baseline assessmentPopulation: The primary outcome measure used the intent-to-treat analysis set, which consisted of all enrolled subjects who got at least 1 dose of paliperidone palmitate and had both a baseline and at least 1 post-baseline efficacy measurement during the study. For imputation of missing time points, last observation carried forward (LOCF) was used.
The PANSS measures the severity of psychotic symptoms of schizophrenia. Scores range from 30 to 210, where 30=best and 210=worst. The change in PANSS total score for all eligible subjects was measured from the beginning of the study to Week 13 (i.e., the end of the double-blind treatment period) or, if the subject left the study early, from the beginning of the study to the last assessment after baseline.
Outcome measures
| Measure |
Paliperidone Palmitate 25 mg eq.
n=155 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
n=161 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
n=160 Participants
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
n=160 Participants
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
|---|---|---|---|---|
|
Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 13 or the Last Post-baseline Assessment
|
-8.0 Scores on a scale
Standard Deviation 19.90
|
-11.6 Scores on a scale
Standard Deviation 17.63
|
-13.2 Scores on a scale
Standard Deviation 18.48
|
-2.9 Scores on a scale
Standard Deviation 19.26
|
SECONDARY outcome
Timeframe: Baseline to 13 weeks or the last post-baseline assessmentPopulation: The secondary outcome measures used the intent-to-treat analysis set, which consisted of all enrolled subjects who got at least 1 dose of paliperidone palmitate and had both a baseline and at least 1 post-baseline efficacy measurement during the study. For imputation of missing time points, last observation carried forward (LOCF) was used.
The PSP scale measures the degree of normal function of a subject in interpersonal relationships and social interactions. Scores range from 1 to 100, where 1 is worst and 100 is best. The average change in PSP score for all eligible subjects was measured from the beginning of the study to Week 13 (i.e., the end of the double-blind treatment period) or, if the subject left the study early, from the beginning of the study to the last assessment after baseline.
Outcome measures
| Measure |
Paliperidone Palmitate 25 mg eq.
n=155 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
n=161 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
n=160 Participants
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
n=160 Participants
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
|---|---|---|---|---|
|
Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 13 or the Last Post-baseline Assessment.
|
2.9 Scores on a scale
Standard Deviation 15.29
|
6.1 Scores on a scale
Standard Deviation 13.59
|
8.3 Scores on a scale
Standard Deviation 14.69
|
1.7 Scores on a scale
Standard Deviation 15.60
|
SECONDARY outcome
Timeframe: Baseline to 13 weeks or the last post-baseline assessmentPopulation: The secondary outcome measures used the intent-to-treat analysis set, which consisted of all enrolled subjects who got at least 1 dose of paliperidone palmitate and had both a baseline and at least 1 post-baseline efficacy measurement during the study. For imputation of missing time points, last observation carried forward (LOCF) was used.
The CGI-S rating scale was used to assess the severity of a subject's overall clinical condition. Scores range from 1 to 7, where 1=best and 7=worst. The change in CGI-S score for all eligible subjects was measured from the beginning of the study to Week 13 (i.e., the end of the double-blind treatment period) or, if the subject left the study early, from the beginning of the study to the last assessment after baseline.
Outcome measures
| Measure |
Paliperidone Palmitate 25 mg eq.
n=155 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
n=161 Participants
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
n=160 Participants
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
n=160 Participants
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
|---|---|---|---|---|
|
Change in Clinical Global Impression-Severity (CGI-S) Scores From Baseline to Week 13 or the Last Post-baseline Assessment
|
-1.0 Scores on a scale
Interval -3.0 to 2.0
|
-1.0 Scores on a scale
Interval -4.0 to 2.0
|
-1.0 Scores on a scale
Interval -4.0 to 3.0
|
0.0 Scores on a scale
Interval -3.0 to 2.0
|
Adverse Events
Paliperidone Palmitate 25 mg eq.
Serious events: 15 serious events
Other events: 27 other events
Deaths: 0 deaths
Paliperidone Palmitate 100 mg eq.
Serious events: 22 serious events
Other events: 27 other events
Deaths: 0 deaths
Paliperidone Palmitate 150 mg eq.
Serious events: 13 serious events
Other events: 28 other events
Deaths: 0 deaths
Placebo
Serious events: 23 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Paliperidone Palmitate 25 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
|---|---|---|---|---|
|
Psychiatric disorders
Schizophrenia
|
5.6%
9/160 • Number of events 11
|
6.1%
10/165 • Number of events 10
|
3.1%
5/163 • Number of events 5
|
6.1%
10/164 • Number of events 10
|
|
Psychiatric disorders
Psychotic disorder
|
1.9%
3/160 • Number of events 3
|
4.2%
7/165 • Number of events 7
|
2.5%
4/163 • Number of events 4
|
4.3%
7/164 • Number of events 7
|
|
Psychiatric disorders
Suicidal ideation
|
1.9%
3/160 • Number of events 3
|
1.2%
2/165 • Number of events 2
|
0.00%
0/163
|
1.8%
3/164 • Number of events 3
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/160
|
0.61%
1/165 • Number of events 1
|
0.61%
1/163 • Number of events 1
|
0.00%
0/164
|
|
Psychiatric disorders
Depression
|
0.62%
1/160 • Number of events 1
|
0.00%
0/165
|
0.61%
1/163 • Number of events 1
|
0.61%
1/164 • Number of events 1
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/160
|
0.61%
1/165 • Number of events 1
|
0.61%
1/163 • Number of events 1
|
0.00%
0/164
|
|
Psychiatric disorders
Agitation
|
0.62%
1/160 • Number of events 1
|
0.00%
0/165
|
0.00%
0/163
|
0.61%
1/164 • Number of events 1
|
|
Psychiatric disorders
Hallucination, auditory
|
0.62%
1/160 • Number of events 1
|
0.00%
0/165
|
0.00%
0/163
|
0.00%
0/164
|
|
Psychiatric disorders
Insomnia
|
0.62%
1/160 • Number of events 1
|
0.00%
0/165
|
0.00%
0/163
|
0.00%
0/164
|
|
Psychiatric disorders
Schizoaffective disorder
|
0.00%
0/160
|
0.61%
1/165 • Number of events 1
|
0.00%
0/163
|
0.00%
0/164
|
|
Psychiatric disorders
Schizophrenia, paranoid type
|
0.00%
0/160
|
0.61%
1/165 • Number of events 1
|
0.00%
0/163
|
0.00%
0/164
|
|
Psychiatric disorders
Acute psychosis
|
0.00%
0/160
|
0.00%
0/165
|
0.00%
0/163
|
0.61%
1/164 • Number of events 1
|
|
Psychiatric disorders
Delusional disorder, persecutory type
|
0.00%
0/160
|
0.00%
0/165
|
0.00%
0/163
|
0.61%
1/164 • Number of events 1
|
|
Psychiatric disorders
Homicidal ideation
|
0.00%
0/160
|
0.00%
0/165
|
0.00%
0/163
|
0.61%
1/164 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/160
|
0.00%
0/165
|
0.61%
1/163 • Number of events 1
|
0.00%
0/164
|
|
Nervous system disorders
Syncope
|
0.62%
1/160 • Number of events 1
|
0.00%
0/165
|
0.00%
0/163
|
0.00%
0/164
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/160
|
0.61%
1/165 • Number of events 1
|
0.00%
0/163
|
0.00%
0/164
|
|
Infections and infestations
Diverticulitis
|
0.62%
1/160 • Number of events 1
|
0.00%
0/165
|
0.00%
0/163
|
0.00%
0/164
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/160
|
0.00%
0/165
|
0.00%
0/163
|
0.61%
1/164 • Number of events 1
|
|
Investigations
Electrocardiogram change
|
0.00%
0/160
|
0.00%
0/165
|
0.00%
0/163
|
0.61%
1/164 • Number of events 1
|
Other adverse events
| Measure |
Paliperidone Palmitate 25 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 25 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 100 mg eq.
Paliperidone palmitate 150 mg eq. (i.m., deltoid muscle) on Day 1, and 100 mg eq. (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator) on Days 8, 36, and 64.
|
Paliperidone Palmitate 150 mg eq.
Paliperidone palmitate 150 mg eq. on Day 1 (i.m., deltoid muscle) and on Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
Placebo
Placebo on Day 1 (i.m., deltoid muscle) and Days 8, 36, and 64 (i.m., gluteal or deltoid muscle, left or right side, at the discretion of the investigator).
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
10.6%
17/160
|
6.7%
11/165
|
6.1%
10/163
|
7.3%
12/164
|
|
Nervous system disorders
Akathisia
|
1.2%
2/160
|
4.8%
8/165
|
5.5%
9/163
|
4.9%
8/164
|
|
General disorders
Injection site pain
|
8.8%
14/160
|
6.1%
10/165
|
8.0%
13/163
|
3.7%
6/164
|
Additional Information
Compound Development Team Leader, Paliperidone
Johnson & Johnson Pharmaceutical Research & Development
Phone: 609-730-4530
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60