Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial. Safety and tolerability of oral paliperidone extended-release tablets in elderly patients with schizophrenia: a double-blind, placebo-controlled study with six-month open-label extension. A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia. Efficacy and safety of paliperidone extended-release tablets: results of a 6-week, randomized, placebo-controlled study. Randomized, double-blind, placebo-controlled study of paliperidone extended-release and quetiapine in inpatients with recently exacerbated schizophrenia. Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomized, placebo-controlled study. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study.
Paliperidone extended-release tablet (paliperidone ER) is an investigational oral psychotropic developed for schizophrenia treatment. It utilizes OROS technology to provide a unique pharmacokinetic profile, eliminating the need for titration and potentially leading to improved tolerability. Furthermore, paliperidone undergoes limited hepatic metabolism.
                The efficacy and safety of once-daily paliperidone ER (6 mg, 9 mg and 12 mg) were assessed versus placebo in 628 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study.
                All doses of paliperidone ER demonstrated significant improvement in PANSS score, all PANSS Marder factor scores (p<0.001) and personal and social functioning versus placebo (p<0.001). The PANSS total score also improved significantly in the olanzapine treatment arm. Significantly higher percentages of paliperidone ER patients demonstrated a > or =30% reduction in PANSS total score versus placebo (p<0.001). The incidence of movement disorder-related AEs and rating scales measurements were similar to placebo for the paliperidone ER 6 mg group and higher in the 9 mg and 12 mg groups. In the paliperidone ER groups there were no reports of glucose-related AEs or clinically relevant changes in plasma lipid levels and changes in mean bodyweight<1 kg.
                In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. Paliperidone ER offers a distinctive treatment profile and may provide a valuable new treatment option for patients with schizophrenia. The objective of this multicenter, international study was to evaluate safety and tolerability of paliperidone extended-release (ER) tablets in elderly (age > or =65 years) patients with schizophrenia. The authors conducted a 6-week, double-blind, randomized, placebo-controlled, optional 24-week open-label extension study. Interventions consisted of flexible, once-daily doses of paliperidone ER (3-12 mg/day; 6-mg starting dose, adjusted in 3-mg dose increments) or placebo (2:1) during double-blind treatment and paliperidone ER only during open-label treatment. Measurements included adverse events, laboratory tests, physical examinations, 12-lead electrocardiograms, movement disorder rating scales, Positive and Negative Syndrome Scale, and Clinical Global Impression scale. The study was not powered to show statistical differences.
                Patients (N = 114) were predominantly female (73%); mean age was 70 years (double-blind phase). Concomitant disease presence was consistent with that of an older population. During the double-blind phase, discontinuation rates resulting from adverse events were similar between groups (paliperidone ER: 7%, placebo: 8%) as were incidences of treatment-emergent adverse events (paliperidone ER: 67%, placebo: 71%). Serious adverse events occurred in 3% of the paliperidone ER- and 8% of the placebo-treated patients. Elevated prolactin levels occurred in approximately one half of patients. No prolactin- or glucose treatment-related adverse events or noteworthy mean changes in body weight (0 kg [standard deviation: 2.1] and 0 kg [standard deviation: 2.3] for paliperidone ER and placebo, respectively) were observed. Safety and tolerability results in the extension were consistent with the shorter-term results. Efficacy measures did not show consistent statistical improvement between treatment groups.
                Paliperidone ER (3-12 mg/day) treatment over a 30-week period was generally well-tolerated and may improve symptom severity in elderly patients with schizophrenia. The effects of paliperidone extended-release on sleep architecture in patients with schizophrenia-related insomnia were evaluated in this multicenter, double-blind, randomized, placebo-controlled study. Patients received paliperidone extended-release 9 mg/day or matching placebo during the 14-day double-blind phase. Sleep architecture and sleep continuity were evaluated using polysomnograms. Subjective sleep measures were evaluated daily using the Leeds Sleep Evaluation Questionnaire. Efficacy and safety were also assessed. Thirty-six patients (17 on paliperidone extended-release, 19 on placebo; mean age 32.2 years) completed the study. Paliperidone extended-release treatment vs. placebo resulted in clinically and statistically significant differences in sleep measurements from baseline to endpoint including a reduction in: persistent sleep latency (41 min), sleep onset latency (35 min), number of awakenings after sleep onset (7), time awake in bed (50 min), and stage 1 sleep duration (12 min); prolongation in: total sleep time (53 min), sleep period time (42 min), stage 2 sleep duration (51 min), and rapid eye movement sleep duration (18 min); and an increase in sleep efficiency index (11%). Paliperidone extended-release, compared with placebo, did not exacerbate daytime somnolence and improved symptoms of schizophrenia. Paliperidone extended-release was well tolerated and improved sleep architecture and sleep continuity in patients diagnosed with schizophrenia and concomitant insomnia. Paliperidone extended-release tablet (paliperidone ER; Invega, Janssen L.P., Titusville, New Jersey) is an oral psychotropic for schizophrenia treatment.
                Efficacy and safety of once-daily paliperidone ER (6 and 12 mg) were assessed versus placebo in 444 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An olanzapine (10 mg) treatment arm was included to confirm trial validity.
                Both doses of paliperidone ER demonstrated significant improvement in Positive and Negative Syndrome Scale (PANSS) total score (p < or = .006) and certain PANSS Marder factor scores compared with placebo (p < or = .025); PANSS total score also improved in the olanzapine treatment arm. Paliperidone ER 6 mg (p < or = .008), but not 12 mg, was associated with significant improvements in personal and social performance. The incidence of treatment-emergent adverse events (AEs) for paliperidone ER 6 mg was comparable with placebo and slightly greater with paliperidone ER 12 mg. Changes in blood glucose and lipid levels with paliperidone ER were comparable with placebo. Two patients treated with paliperidone ER experienced glucose-related AEs. Body-weight increases of 1-2 kg were observed with paliperidone ER. Although there were increases in plasma prolactin levels with paliperidone ER treatment, the incidence of prolactin-related AEs was < or =1%.
                In this study, paliperidone ER, particularly the 6-mg dose, was effective and well tolerated, and provides a valuable new treatment option for schizophrenia. The authors compared paliperidone extended-release and quetiapine in patients with recently exacerbated schizophrenia requiring hospitalization.
                In a 6-week double-blind study, inpatients with a recent exacerbation of schizophrenia were randomly assigned to treatment with paliperidone extended-release, quetiapine, or placebo. A 2-week monotherapy phase was followed by a 4-week additive-therapy phase. Target doses were at the upper end of recommended ranges: paliperidone extended-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. The primary endpoint was the difference in mean total change score on the Positive and Negative Syndrome Scale (PANSS) between paliperidone extended-release and quetiapine at the 2-week monotherapy phase endpoint.
                Six-week completion rates were 77.5% (124/160) with paliperidone extended-release, 66.7% (106/159) quetiapine, and 63.8% (51/80) placebo. Improvement in mean PANSS total change score was greater with paliperidone extended-release than with quetiapine from day 5 (-11.4 versus -8.2) through the monotherapy phase endpoint (-23.4 versus -17.1). Only paliperidone extended-release showed significantly greater PANSS improvement compared with placebo at 2 weeks. At the 6-week study endpoint, there was a significantly greater improvement with paliperidone extended-release compared with quetiapine despite similar use of additive therapy (predominantly other antipsychotics). Common adverse events with paliperidone extended-release, quetiapine, and placebo, respectively, were tremor (13.9%, 5.0%, 7.5%), somnolence (8.9%, 11.9%, 1.3%), insomnia (10.1%, 9.4%, 11.3%), and headache (12.0%, 7.5%, 13.8%). Six-week adverse event-related discontinuation rates were 6.3%, 10.1%, and 6.3%, respectively, in the paliperidone extended-release, quetiapine, and placebo groups.
                Compared with quetiapine, paliperidone extended-release improved symptoms earlier and to a greater degree in patients with recently exacerbated schizophrenia requiring hospitalization, with no unexpected tolerability findings. Paliperidone extended-release tablet (paliperidone ER) is an oral psychotropic agent developed for schizophrenia treatment. Paliperidone (9-OH-risperidone, metabolite of risperidone), when used with OROS technology has a unique pharmacokinetic profile undergoing limited hepatic metabolism.
                The efficacy and safety of once-daily paliperidone ER (3 mg, 9 mg and 15 mg) were compared with placebo in 618 patients with acute schizophrenia in a 6-week, multicenter, double-blind, randomized, parallel-group study. An assay sensitivity group with known efficacy was included to confirm trial validity (olanzapine 10 mg).
                All doses of paliperidone ER demonstrated significant improvements in PANSS total and PANSS factors scores (p<0.05) and in personal and social functioning (p<0.001) compared with placebo. Symptom improvement has been observed at the first observation assessment (Day 4) (p<0.001) compared with placebo, suggesting a rapid onset of action for paliperidone ER. Paliperidone ER was associated with a low incidence of treatment-emergent adverse events. The incidence of movement disorder-related adverse events and rating scale scores were similar in the paliperidone ER 3 mg and placebo groups and increased with dose. Increases in prolactin plasma levels and dose-related increases in body weight (<2 kg) were observed; there were no significant changes in serum lipid or glucose levels.
                In this study, all doses of paliperidone ER were effective in significantly improving the symptoms of schizophrenia and personal and social functioning and were generally well tolerated. As such, paliperidone ER may provide a valuable new treatment option for patients with schizophrenia. We evaluated the efficacy of paliperidone extended-release (ER), an investigational psychotropic agent, in delaying symptom recurrence in adult patients with schizophrenia and its safety and tolerability. In this randomized, double-blind, placebo-controlled, multicenter study, patients' symptoms were stabilized during an 8-week run-in and a 6-week stabilization phases using open-label, flexibly dosed paliperidone ER (3-15 mg once daily, starting dose = 9 mg). The primary efficacy variable was the time of first recurrence of schizophrenia symptoms, which included predefined changes in symptom scores, psychiatric hospitalization, self-injury, and suicidal or aggressive behavior during the double-blind phase (paliperidone ER or placebo treatment). Based on positive efficacy, the study was terminated at the preplanned interim analysis (43 recurrence events). The interim analysis (primary analysis) included 113 patients (mean age = 41 years; 51% men, 85% white). In the intent-to-treat group, 14 paliperidone ER-treated patients (25%) experienced a recurrence event versus 29 (53%) for placebo. Time-to-recurrence was significantly different, favoring the paliperidone ER group (P = 0.005, log-rank test): 25% quantile of time-to-recurrence was 83 days (paliperidone ER) versus 23 days (placebo). Final analyses (n = 205) were confirmatory. During initial open-label treatment with paliperidone ER, symptoms improved significantly. This improvement was maintained with continued treatment, as were functioning and quality-of-life measures. Treatment-emergent adverse events rates were similar: 35% for paliperidone ER and 40% for placebo. Paliperidone ER treatment versus placebo significantly delayed time-to-recurrence in patients with schizophrenia, maintained symptom stability and measures of functioning, and was generally well tolerated in this patient population.
In short-term studies, oral paliperidone is an antipsychotic drug that is more efficacious than placebo. We found its adverse effects to be similar to those of its parent compound, risperidone, with movement disorders, weight gain and tachycardia all more common with paliperidone than placebo. While no difference was found in the incidence of reported adverse sexual outcomes, paliperidone is associated with substantial increases in serum prolactin. When used at doses of 6 mg per day or higher, oral paliperidone appears comparable in efficacy to olanzapine 10 mg/day. A single study of six days duration found neither an advantage nor disadvantage of paliperidone compared to risperidone. When dosed flexibly with other psychotropics available, it appears to be comparable in efficacy to flexible doses of quetiapine with other psychotropics available.