Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

Bossie, Cynthia A; Sliwa, Jennifer K; Yi-Wen Ma; Dong-Jing Fu; Alphs, Larry
January 2011
BMC Psychiatry;2011, Vol. 11 Issue 1, p79
Academic Journal
Background: Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid) injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal). These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability. Methods: In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively) or placebo (NCT#00590577). Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS) score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity) using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE) rates and relative risks (RR) with 95% confidence intervals (CI) versus placebo were determined. Results: Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS) mean PANSS total score at Day 8 (p = 0.037). After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ⩽ 0.007 vs. placebo) and Day 36 (p < 0.001). Taken together with results in the 39 mg and 234 mg Day 8 arms, these findings suggest a trend towards a dose-dependent response. During Days 1 to 7, AEs reported in ⩾2% of paliperidone palmitate subjects (234 mg) and a greater proportion of paliperidone palmitate than placebo subjects were: agitation (3.2% vs. 1.3%; RR 2.52 [95% CI 0.583, 10.904]), headache (4.0% vs. 3.8%; RR 1.06 [95% CI 0.433, 2.619]), and injection site pain (6.7% vs. 3.8%; RR 1.79 [95% CI 0.764, 4.208]). Days 8 to 36 AEs meeting the same criteria in the 156 mg Day 8 arm were: anxiety (3.1% vs. 2.5%; RR 1.24 [95% CI 0.340, 4.542]), psychotic disorder (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), dizziness (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]), and injection site pain (2.5% vs. 1.3%; RR 1.99 [95% CI 0.369, 10.699]). Corresponding Days 8 to 36 AEs in the 39 mg Day 8 group were: agitation (4.5% vs. 4.4%; RR 1.03 [95% CI 0.371, 2.874]), anxiety (3.9% vs. 2.5%; RR 1.55 [95% CI 0.446, 5.381]), and psychotic disorder (2.6% vs. 1.3%; RR 2.07 [95% CI 0.384, 11.110]) while in the 234 mg Day 8 group it was anxiety (3.1% vs. 2.5%, RR 1.25 [95% CI 0.342, 4.570]) Conclusions: Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1) compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose-dependent response. No unexpected tolerability findings were noted in the first week or month after the initiation dosing. Trial registration: ClinicalTrials.gov: NCT#00590577


Related Articles

  • The Pulse on Study Conduct. Weeks-Rowe, Elizabeth // CenterWatch Weekly;1/20/2014, Vol. 18 Issue 3, p6 

    The article reports on developing successful relationships with investigational sites in clinical research. It is said that collective research for advanced therapeutics includes a dynamic conviction to push forward, despite challenges. Despite the growing number of participants, clinical...

  • Evolution and Translation of Research Findings: From Bench to Where? Ioannidis, John P. A. // PLoS Clinical Trials;Nov2006, Vol. 3 Issue 11, p0001 

    The credibility and replication of research findings evolve over time, as data accumulate. However, translation of postulated research promises to real-life biomedical applications is uncommon. In some fields of research, we may observe diminishing effects for the strength of research findings...

  • How does long-term odor deprivation affect the olfactory capacity of adult mice? Angely, Cathy J.; Coppola, David M. // Behavioral & Brain Functions;2010, Vol. 6, p26 

    Background: Unilateral naris occlusion (UNO) has been the most common method of effecting stimulus deprivation in studies of olfactory plasticity. However, despite the large corpus on the effects of this manipulation, dating back to the 19th century, little is known about its behavioral sequela....

  • Imaging.  // Nature Reviews Drug Discovery;Dec2009, Vol. 8 Issue 12, p1003 

    Imaging technologies are increasingly being applied to aid translational research — for example, by allowing drug–target interactions to be monitored in clinical trials. Our two interviewees this month describe their careers in this field.

  • Improving Knowledge and Attitudes towards Depression: a controlled trial among Chinese medical students. Ye Rong; Glozier, Nick; Luscombe, Georgina M.; Davenport, Tracey A.; Yueqin Huang; Hickie, Ian B. // BMC Psychiatry;2011, Vol. 11 Issue 1, p36 

    Background: Establishing an evidence-based method of improving knowledge and attitudes concerning depression has been identified as a priority in Chinese medical education. The purpose of this study was to determine whether a self-directed learning strategy as a part of student-centred education...

  • Collaborative care for patients with bipolar disorder: a randomised controlled trial.  // BMC Psychiatry;2011, Vol. 11 Issue 1, p133 

    The article presents a research which describes and examines the study protocol for investigating the effectiveness of Collaborative Care (CC) for patients with bipolar disorder in the Netherlands. It is reported that, the researchers carried out two-armed cluster randomised clinical trial to...

  • Outcomes of Usual Chiropractic, Harm & efficacy, the OUCH study: study protocol for a randomized controlled trial.  // Trials;2011, Vol. 12 Issue 1, p235 

    The article presents a research which examines the frequency and severity of adverse effects from as well as efficacy of short term usual chiropractic treatment of spinal pain when compared to a sham intervention. It is reported that, the researchers carried out randomized controlled trial to...

  • Perinatal pathology in the context oF a clinical trial: a review of the literature. Snowcion, C.; Elbourne, D. R.; Garcia, J. // Archives of Disease in Childhood -- Fetal & Neonatal Edition;May2004, Vol. 89 Issue 3, pF200 

    Perinatal postmortem rates are declining world wide. In the United Kingdom, perinatal pathology has recently been seriously undermined by controversy. There are important consequences for perinatal trials that include pathology studies. This review looks at the reasons for the decline in...

  • Normalisation process theory: a framework for developing, evaluating and implementing complex interventions. Murray, Elizabeth; Treweek, Shaun; Pope, Catherine; MacFarlane, Anne; Ballini, Luciana; Dowrick, Christopher; Finch, Tracy; Kennedy, Anne; Mair, Frances; O'Donnell, Catherine; Bie Nio Ong; Rapley, Tim; Rogers, Anne; May, Carl // BMC Medicine;2010, Vol. 8, p63 

    Background: The past decade has seen considerable interest in the development and evaluation of complex interventions to improve health. Such interventions can only have a significant impact on health and health care if they are shown to be effective when tested, are capable of being widely...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics