A total of 480 patients were enrolled. Among them, a total of 426 subjects (88.8%) had evaluation at week 4 and 350 (72.9%) completed the 12-week evaluation. The details of patient disposition are summarized in Figure .
Patient Disposition. A total of 480 patients were enrolled. Among them, a total of 426 subjects (88.8%) had evaluation at week 4 and 350 (72.9%) completed the 12-week evaluation. The details of patient disposition are summarized.
Reasons of patient withdrawal before week 4 were AEs (n = 6), insufficient response (n = 2), ineligible to continue (n = 15), lost to follow-up (n = 12), consent withdrawn (n = 16), and noncompliance (n = 3). Therefore these 54 patients did not have any safety and efficacy evaluation, resulting in 426 subjects included in the ITT population.
The initial dose disposition at baseline for these 426 patients was 3 mg/day for 154 patients, 6 mg/day for 232 patients, 9 mg/day for 29 patients, and 12 mg/day for 11 patients. The average dosage was 5.5 mg/day. The end doses for 350 subjects who completed the study were distributed as 45 patients with 3 mg/day, 183 patients with 6 mg/day, 64 patients with 9 mg/day, and 58 patients with 12 mg/day.
The withdrawal reasons are summarized in Table . Overall, 130 subjects (27.1%) discontinued the study prematurely. The details are as follows: 1 subject (0.2%) died, 12 subjects (4.8%) withdrew because of adverse events, 18 (3.8%) subjects withdrew because of insufficient response, 15 subjects (3.1%) were ineligible to continue, 28 subjects (5.8%) were lost to follow-up, 35 subjects (7.3%) withdrew their consent, 8 (1.7%) subjects discontinued because of non-compliance, and 2 subjects (0.4%) because of other reasons.
Summary of Withdrawal Reason
Summary statistics of demographic characteristics for the overall and ITT populations are listed in Table . In the ITT population, there were more men (55.9%) than women (44.1%). The mean age was 40.4 (range, 17-72) years; median age was 40 years. Subjects' schizophrenia subtype distribution was paranoid 61.7%, undifferentiated 18.9%, disorganized 10.8%, residual 7.3%, catatonic 1.2%, and other subtypes 0.2%. Overall, 33.3% of the subjects had symptom onset > 10 years but < 20 years. There were 4.9% of subjects with history of drug abuse. The results of all enrolled subjects were similar to those of the ITT population.
The reasons for subjects switching their treatments are displayed for all enrolled patients and the ITT population in Figures and , respectively. For the ITT population, there were 4 subjects who did not receive any antipsychotics at enrollment. For the remaining 422 subjects, 409 received antipsychotics within 30 days prior to enrollment. The treatments included oral risperidone for 188 subjects (45.97%), olanzapine for 40 subjects (9.78%), quetiapine for 29 subjects (7.09%), aripiprazole for 28 subjects (6.85%), and other treatments for 166 subjects (40.59%). The major reason of switching treatment was insufficient efficacy, accounting for a total of 321 subjects. AEs (82 subjects), noncompliance (42 subjects), and other (2 subjects) were the reasons for switching. Thirteen subjects received antipsychotics > 30 days prior to enrollment. The switching reasons were insufficient efficacy (n = 7), noncompliance (n = 6), and other (n = 1).
Figure 2 Summary of switching reasons of previous antipsychotic treatment of all enrolled patients. For the enrolled population, there were 9 subjects who did not receive any antipsychotics at enrollment. For the remaining 471 subjects, 449 received antipsychotics (more ...)
Figure 3 Summary of switching reasons of previous antipsychotic treatment of ITT population. For the ITT population, there were 4 subjects who did not receive any antipsychotics at enrollment. For the remaining 422 subjects, 409 received antipsychotics within (more ...)
Table summarizes previous antipsychotic treatment received for consecutive 3 months. The most frequently used antipsychotics were oral risperidone (207 subjects; 48.6%) for the ITT population. The results of all enrolled subjects were similar to those of the ITT population.
Summary of Previous Antipsychotics Treatment Received for Consecutive 3 Months
Table summarizes the complicating diseases for subjects. For the ITT population, the most commonly complained complications were psychiatric (329 subjects; 77.23%), gastrointestinal (145 subjects; 34.04%), and neurological disorders (104 subjects; 24.41%), respectively.
Table 4 Summary of Concurrent Disease with Incidence 5%
Dose disposition of study medication paliperidone ER of the ITT population and completed population is presented in Table and Table , respectively. In the ITT population, the number of subjects who started paliperidone ER treatment with the initial dose of 3 mg/day and increased to 6, 9, and 12 mg/day at the end of study was 69, 17, and 18, respectively. There were 43 and 30 subjects with the initial dose of 6 mg/day and increased to 9 and 12 mg/day, respectively, at the end of study, whereas 11 subjects with the initial dose of 9 mg/day increased to 12 mg/day at the end of study. All subjects with initial dose of 12 mg/day remained on 12 mg/day till the end of study. The completed population had a similar dose pattern of study dose disposition.
Summary of Dose Disposition of ITT Population
Summary of Dose Disposition of Complete Study Subjects
PANSS and PAP total score both showed significant improvements after 12-week treatment (PANSS score, from 89.88 ± 29.20 to 72.72 ± 26.36; PSP score, from 47.07 ± 16.34 to 56.61 ± 14.32; both p < 0.05). The results of symptomatic remission are summarized in Figure . The symptomatic remission rate was 3.5% (95%CI, 1.98%, 5.74%) at baseline and improved to 11.7% (95%CI, 8.84%, 15.18%) at the end of study (p < 0.05). The criteria for PSP improvement was at least one 10-point interval on PSP scale. In the ITT population, subjects showed an increasing PSP improvement after treatment began. The improvement rate was increased from 28.1% (95%CI, 23.94%, 32.70%) at week 4 to 47.4% (95%CI, 42.59%, 52.28%) at the end of study.
Figure 4 Summary of Efficacy Result. The symptomatic remission rate was 3.5% (95%CI, 1.98%, 5.74%) at baseline and improved to 11.7% (95%CI, 8.84%, 15.18%) at the end of study (p < 0.05). The criteria for PSP improvement was at least one 10-point interval (more ...)
AEs with occurrence ≥ 2% during the study are summarized in Table . There were 213 patients (50.0%) with ≥ 1 AE during study. The most commonly experienced AEs were disease progression (33 patients; 7.7%), upper respiratory tract infection (30 patients; 7.0%), extrapyramidal disorder (25 patients; 5.2%), insomnia (17 patients; 4.0%), and constipation (14 patients; 3.3%). Among the 30 schizophrenia events 27 were recorded as serious AEs.
Table 7 Adverse Events with Incidence 2%