Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia (original) (raw)
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Early intervention in psychiatry, 2015
Long-acting injectable antipsychotics (APs) are not well studied in recent-onset schizophrenia. This exploratory analysis of a study designed to reflect real-world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once-monthly paliperidone palmitate (PP) and daily oral APs in patients with recent-onset or chronic illness METHODS: This randomized, open-label, event monitoring board-blinded study compared treatment response in subjects with schizophrenia and a history of criminal justice system involvement following treatment with PP or oral APs for 15 months (ClinicalTrials.gov identifier, NCT01157351). Event-free probabilities were estimated using Kaplan-Meier method; hazard ratios (HRs) were estimated using Cox proportional hazard models. This subgroup analysis analysed data by disease duration (≤5 (recent-onset) or >5 years (chronic illness) since first psychiatric diagnosis). Seventy-seven subjects met the criteria fo...
The Journal of Clinical Psychiatry, 2015
Designed to reflect real-world issues in the treatment of schizophrenia 1 ✓ Prospective ✓ Randomized ✓ Open-label with blinded Event Monitoring Board ✓ A 15-month, head-to-head trial vs commonly prescribed oral antipsychotics* ✓ Flexible treatment interventions • Oral antipsychotics could be deselected prior to randomization • Allowed dosing flexibility and use of concomitant medications ✓ Included patients who are typically excluded from clinical trials • Comorbid substance abuse † • History of incarceration ‡ • Unstable living conditions ✓ Medication adherence was monitored but not required to complete the trial Real-world design elements Clinical trial features
Schizophrenia Research, 2016
Background: Persons with schizophrenia often come in contact with the criminal justice system (CJS). This analysis of subjects with schizophrenia and a history of contact with the CJS estimated and compared mean cumulative function (MCF) of treatment failure events when treated with paliperidone palmitate (PP) or oral antipsychotics (OAs). All events identified during the full study period of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) trial were evaluated. Methods: Subjects were randomly assigned to flexibly dosed, monthly, injectable PP (78-234 mg) or daily OA in a 15-month prospective, open-label, multicenter US study (May 5, 2010-December 9, 2013). Subjects could continue participation after a treatment failure event. Multiple treatment failures in individual subjects were analyzed as recurrent events. Analyses estimated MCF of treatment failure events and MCF of institutionalizations (arrests, incarcerations, or psychiatric hospitalizations) during the 15-month study period. Results: The ITT population included 226 (PP) and 218 (OA) subjects, of whom 41.2% and 40.4%, respectively, completed 15 months of follow-up. The MCF of treatment failures and institutionalizations differed significantly in favor of PP compared with OA (P = 0.007 and P = 0.005, respectively). Overall, TEAEs were reported by 86.3% of subjects in the PP group and 81.7% in the OA group. Conclusions: This pragmatic analysis suggests that, compared with OA, PP is not only more effective in delaying median time to treatment failure, but it also reduces the number of treatment failures and institutionalizations per person-year follow-up. Clinical trials registration: Clinicaltrials.gov identifier: NCT01157351
Expert Opinion on Pharmacotherapy, 2016
Objective: To explore the treatment response, tolerability and safety of once-monthly paliperidone palmitate (PP1M) in non-acute patients switched from oral antipsychotics, stratified by time since diagnosis as recently diagnosed (≤3 years) or chronic patients (>3 years). Research design and methods: Post hoc analysis of a prospective, interventional, single-arm, multicentre, open-label, 6-month study performed in 233 recently diagnosed and 360 chronic patients. Main outcome measures: The proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to endpoint) and maintained efficacy (defined as non-inferiority in the change in PANSS total score at endpoint [Schuirmann's test]). Results: 71.4% of recently diagnosed and 59.2% of chronic patients showed a ≥20% decrease in PANSS total score (p = 0.0028 between groups). Changes in PANSS Marder factors, PANSS subscales, and the proportion of patients with a Personal and Social Performance scale (PSP) total score of 71-100 were significantly greater in recently diagnosed compared with chronic patients. PP1M was well tolerated, presenting no unexpected safety findings. Conclusion: These data show that recently diagnosed patients treated with PP1M had a significantly higher treatment response and improved functioning, as assessed by the PSP total score, than chronic patients.
Neuropsychiatric disease and treatment, 2015
To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics. In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18-50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50-150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods. A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18...
The International Journal of Neuropsychopharmacology, 2016
Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18-70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150 mg eq. deltoid], day 8 [100 mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150 mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525 mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150 mg eq. deltoid/ gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n = 504; PP1M: n = 512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n = 37, 8%; PP1M: n = 45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia.
International Journal of Neuropsychopharmacology, 2021
Background This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia. Methods Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen. Results Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Mei...
Paliperidone palmitate versus oral antipsychotics in recently diagnosed schizophrenia
Schizophrenia Research, 2015
Objective: Relapse and acute exacerbation are common in schizophrenia and may impact treatment response and outcome. Evidence is conflicting in respect to superiority of long-acting injectable antipsychotic therapies versus oral antipsychotics in relapse prevention. This randomized controlled study assessed the efficacy of paliperidone palmitate versus oral antipsychotics for relapse prevention. Method: Eligible patients with a recent diagnosis of schizophrenia (within 1-5 years) were randomized 1:1 to paliperidone palmitate (n = 376) or oral antipsychotic monotherapy (n = 388) and entered a 2-week initial acute oral treatment phase. Patients who met predefined response criteria were eligible to enter the 24-month rater-blinded core treatment phase. Patients were evaluated for relapse, symptoms, functioning, quality of life, treatment satisfaction, and tolerability. Results: In the core treatment phase, time to relapse was significantly longer in the paliperidone palmitate (n = 352) compared with the oral antipsychotics arm (n = 363): 85% of patients were relapse-free at 469 versus 249 days (P = 0.019). Significantly fewer patients receiving paliperidone palmitate met the relapse criteria (52 [14.8%] versus 76 [20.9%, oral antipsychotics]; P = 0.032), representing a 29.4% relative risk reduction. For paliperidone palmitate, a significantly greater improvement in Positive and Negative Syndrome Scale total score on Day 8 (P = 0.021) and a trend at endpoint (P = 0.075) were observed. Functioning improvements were comparable between treatment arms. No new safety signals were identified. Conclusion: The observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia, including during the early stages of illness.
The Journal of Clinical Psychiatry, 2014
Background: Public health considerations require that clinical trials address the complex "real-world" needs of patients with chronic illnesses. This is particularly true for persons with schizophrenia, whose management is frequently complicated by factors such as comorbid substance abuse, homelessness, and contact with the criminal justice system. In addition, barriers to obtaining health care in the United States often prevent successful community reentry and optimal patient management. Further, nonadherence to treatment is common, and this reinforces cycles of relapse and recidivism. Long-acting injectable antipsychotic therapy may facilitate continuity of treatment and support better outcomes, particularly in patients who face these challenges. Clinical trials with classical explanatory designs may not be the best approaches for evaluating these considerations. We describe the design and rationale of a novel trial that combines both explanatory and pragmatic design features and studies persons with schizophrenia who face these challenges. Design and Rationale: The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study is a prospective, open-label, randomized, 15-month study conducted between May 5, 2010, and December 9, 2013, comparing long-acting injectable paliperidone palmitate and oral antipsychotic medications in subjects with schizophrenia (according to DSM-IV criteria). Investigators and subjects had broad flexibility for treatment decision-making, thus making it a model that better reflects real-world practice. The primary end point was time to treatment failure, defined as arrest/incarceration psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization. This end point was adjudicated by a blinded event monitoring board. Patients were followed to the 15-month end point, regardless of whether they were maintained on their initial randomized treatment. This article provides some of the reasoning behind the authors' choices when combining features from both explanatory and pragmatic approaches to this trial's design. Conclusions: The PRIDE study incorporates real-world design features in a novel, prospective, comparative study of long-acting injectable and oral antipsychotics in persons with schizophrenia who have had recent contact with the criminal justice system. Insights provided should help the reader to better understand the need for more real-world approaches for clinical studies and how a broader approach can better aid clinical treatment and public health decision-making.
Journal of Comparative Effectiveness Research, 2015
To assess impact of initial treatment and time-dependent treatment with paliperidone palmitate (PP) versus oral atypical antipsychotics (OAAs) on healthcare resource utilization and costs. Patients & methods: A retrospective longitudinal study was conducted among Medicaid beneficiaries with schizophrenia. Inverse probability treatment weighting method and marginal structural models were used to estimate the impact of treatment on healthcare resource utilization and costs, respectively. Results: