Dataset Information

Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial.

ABSTRACT: BACKGROUND:This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population. METHODS:Subjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively]) or placebo. This subgroup analysis included those with a baseline Clinical Global Impressions-Severity (CGI-S) score indicating marked to severe illness. PP subjects received a 234-mg day 1 injection (deltoid), followed by their assigned dose on day 8 and monthly thereafter (deltoid or gluteal). Thus, data for PP groups were pooled for days 4 and 8. Measures included Positive and Negative Syndrome Scale (PANSS), CGI-S, Personal and Social Performance (PSP), and adverse events (AEs). Analysis of covariance (ANCOVA) and last-observation-carried-forward (LOCF) methodologies, without multiplicity adjustments, were used to assess changes in continuous measures. Onset of efficacy was defined as the first time point a treatment group showed significant PANSS improvement (assessed days 4, 8, 22, 36, 64, and 92) versus placebo, which was maintained through end point. RESULTS:A total of 312 subjects met inclusion criterion for this subgroup analysis. After the day 1 injection, mean PANSS total scores improved significantly with PP (all received 234 mg) versus placebo at day 4 (P = 0.012) and day 8 (P = 0.007). After the day 8 injection, a significant PANSS improvement persisted at all subsequent time points in the 234-mg group versus placebo (P < 0.05). PANSS improvements were greater from day 36 through end point in the 156-mg group (P < 0.05) and only at end point in the 39-mg group (P < 0.05). CGI-S and PSP scores improved significantly in the 234-mg and 156-mg PP groups versus placebo at end point (P < 0.05 for both, respectively); improvement in the 39-mg group was not significant. The most common AEs for PP-treated subjects (?10%, any treatment group) were headache, insomnia, schizophrenia exacerbation, injection site pain, and agitation. CONCLUSIONS:In this markedly to severely ill population, acute treatment with 234 mg PP improved psychotic symptoms compared with placebo by day 4. After subsequent injections, observed improvements are suggestive of a dose-dependent effect. No unexpected tolerability findings were noted.

SUBMITTER: Alphs L

PROVIDER: S-EPMC3082227 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial.

Alphs Larry L Bossie Cynthia A CA Sliwa Jennifer K JK Ma Yi-Wen YW Turner Norris N

Annals of general psychiatry 20110411 1

<h4>Background</h4>This post hoc analysis (trial registration: ClinicalTrials.gov NCT00590577) assessed onset of efficacy and tolerability of acute treatment with once-monthly paliperidone palmitate (PP), a long-acting atypical antipsychotic initiated by day 1 and day 8 injections, in a markedly to severely ill schizophrenia population.<h4>Methods</h4>Subjects entering the 13-week, double-blind trial were randomized to PP (39, 156, or 234 mg [25, 100, and 150 mg eq of paliperidone, respectively] ...[more]

PMID: 21481243

Similar Datasets

Project description:BackgroundThis post hoc subgroup analysis of a randomized, double-blind trial evaluated the response to treatment with two long-acting injectable atypical antipsychotics, ie, paliperidone palmitate and risperidone long-acting injectable (RLAI), in subjects with schizophrenia experiencing clinically significant symptoms despite recent treatment with oral risperidone only or other oral antipsychotics.MethodsAdult subjects were eligible for the 13-week, double-blind, double-dummy trial (NCT00589914) if they had an established diagnosis of schizophrenia for at least one year and a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 inclusive at screening. Subjects received either paliperidone palmitate (234 mg, day 1; 156 mg, day 8; then once-monthly flexible dosing) or RLAI (25-50 mg biweekly, with oral risperidone supplementation on days 1-28), plus matched placebo injections/tablets.ResultsThis post hoc analysis reports data on 747 subjects who, within 2 weeks of starting double-blind study medication, had reportedly received oral risperidone only (paliperidone palmitate group, n = 126; RLAI group, n = 107), other oral antipsychotics (paliperidone palmitate group, n = 199; RLAI group, n = 203), or no antipsychotic (paliperidone palmitate group, n = 56; RLAI group, n = 56). Mean PANSS total scores improved significantly at end point across all subgroups (mean change from baseline ranged from -17.5 to -19.5, all P < 0.0001). Clinical Global Impression-Severity and Personal and Social Performance scale measures also significantly improved from baseline (all P < 0.0001).ConclusionTreatment with paliperidone palmitate or RLAI resulted in a significant reduction in the symptoms of schizophrenia irrespective of previous recent treatment with oral risperidone only or other oral antipsychotics. For subjects who had previously received oral risperidone only, the difference in formulation was the main change in the intervention because the molecule delivered remained the same or similar. These data support the contribution of a long-acting formulation to improving the treatment response and suggest that nonadherence may be a significant contributor to inadequate efficacy of oral formulations in subjects with schizophrenia.

Project description:ObjectiveFirst-month data of a 13-week acute schizophrenia study were used to compare paliperidone palmitate to oral risperidone during initiation of long-acting injectable risperidone.DesignDouble-blind, randomized study.SettingOutpatient or inpatient.ParticipantsAdults with established (≥1 year) schizophrenia. Those assigned to risperidone long-acting injectable (n=460) received 25mg on Days 8 and 22 with oral risperidone (l-6mg) supplementation for the first 28 days. The paliperidone palmitate group (n=453) received 150mg eq. on Day 1, l00mg eq. on Day 8, and oral placebo supplementation for the first 28 days.MeasurementsPositive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical Global Impression-Severity score, and responder rate (percentage of patients with ≥30% reduction in PANSS total score). An analysis of covariance model estimated least-square mean differences between treatment groups. A post-hoc analysis of efficacy data for the period of interest, i.e., at the time points before and after the first 28 days, was conducted.ResultsPositive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical global Impression-Severity scores showed similar efficacy between the treatment groups during the first weeks of treatment, corresponding to the risperidone long-acting injection initiation period. Mean Positive and Negative Syndrome Scale total score at baseline was 84.7 for paliperidone palmitate and 84.4 for oral risperidone, on Day 22 was 73.6 and 74.1, respectively, and on Day 36 was 71.8 and 72.8, respectively. Overall incidence of adverse events in the first 28 days was generally similar (45% for paliperidone palmitate vs. 35% for oral risperidone), except for injection site pain (4.6% vs. 0.7%). Similar active moiety plasma concentrations were obtained during this period.ConclusionDuring the first month, paliperidone palmitate without oral supplementation has similar efficacy and safety to oral risperidone (during initiation of risperidone long-acting injectable) in acutely exacerbated schizophrenia.

Project description:BackgroundA post hoc analysis from a multiphase trial with open-label transition and maintenance phases, a double-blind relapse prevention phase, and an optional open-label extension examined the long-term tolerability with continuous once-monthly injectable paliperidone palmitate 39, 78, 117, or 156 mg (25, 50, 75, or 100 mg equivalents [mg eq] of paliperidone) in subjects with recently diagnosed (≤5 years; n = 216) versus chronic illness (>5 years; n = 429) schizophrenia.MethodsAdverse events reported at a ≥2% margin between subgroups were identified. Relative risks (in the recently diagnosed compared with the chronically ill) and 95% confidence intervals (CI) were determined, and CI not including 1 were considered potentially significant.ResultsIn both subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean exposures were 333.9 ± 271.9 and 308.7 ± 278.3 days in the recently diagnosed and chronic illness subgroups, respectively. Using the criteria outlined in the methods, nasopharyngitis was a potentially significant event reported in more chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163-0.907). Influenza (2.8% versus 0.7%; relative risk 3.9; 95% CI 1.003-15.730) and amenorrhea (3.2% versus 0.9%; relative risk 3.476; 95% CI 1.029-11.744) at endpoint were potentially significant events in more recently diagnosed than chronically ill subjects. Mean weight changes, sedation/somnolence, any extrapyramidal symptom-related or glucose-related events were generally similar between the groups. The mean prolactin level increased in both sexes in both subgroups (changes from baseline of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically ill.ConclusionThe long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.

Project description:BackgroundTreatment of schizophrenia requires long-term medication to prevent relapse. Treatment nonadherence may increase the risk of relapse, leading to increased hospitalizations and emergency room (ER) visits. Long-acting injectables (LAIs) such as paliperidone palmitate have improved treatment adherence and therefore symptoms. However, real-world studies comparing 3-monthly LAI formulations with other LAIs and oral antipsychotics (OAs) are scarce.ObjectiveThe objective of this study was to investigate and evaluate the clinical effectiveness of paliperidone palmitate LAI monthly (PP1M; Xeplion®) and 3-monthly (PP3M; Trevicta®) formulations compared with the monthly LAI aripiprazole (AM; Abilify Maintena®) and OAs in Spain.MethodsThis was a retrospective, observational study including 2275 adult patients with schizophrenia in a Spanish population. Data from hospital, primary care, and pharmacy dispensation electronic medical records were obtained between January 2017 and February 2018. The main outcomes included psychiatric hospitalizations and ER visit rates, days on treatment, and treatment persistence.ResultsPatients receiving PP3M had a significantly lower mean hospitalization rate (0.00046 ± standard deviation [SD] 0.00181; p < 0.0001) than other treatment groups. Kaplan-Meier curves revealed that 92.0 and 88.4% of patients receiving PP3M remained hospitalization free by 12 and 18 months, respectively. All treatment groups had at least a twofold significantly higher risk of psychiatric hospitalizations compared with those receiving PP3M or OAs, and the hospitalization risk among the PP3M group was significantly lower (hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.31-0.67). The risk of ER visits was significantly lower with both PP3M and PP1M than with OAs, and lowest with PP3M (HR 0.462 [95% CI 0.29-0.62] and HR 0.833 [95% CI 0.59-0.97], respectively). Time until treatment switch with PP3M was high, with more than 86.5% of patients remaining on treatment at 18 months.ConclusionsPP3M was more effective than OAs and monthly LAIs in improving clinical outcomes for patients with schizophrenia in a real-world setting in Spain.

Dataset Information

Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial.

Publications

Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets