A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia.

Johnson & Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ 08560, USA.
Journal of clinical psychopharmacology (Impact Factor: 5.09). 06/2010; 30(3):235-44. DOI: 10.1097/JCP.0b013e3181dd3103
Source: PubMed

ABSTRACT This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate (approved in the USA, August 2009) for adult patients with acutely exacerbated schizophrenia. The patients (N = 652) were randomly assigned (1:1:1:1) to paliperidone palmitate at 25, 100, or 150 mg eq. or placebo in this 13-week double-blind study. The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or gluteal [corrected] on day 8 and then once monthly (days 36 and 64). No oral supplementation was used. Target plasma levels were achieved by day 8 in all paliperidone palmitate groups. The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly (P < or = 0.034) in all the paliperidone palmitate dose-groups versus placebo. Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle. Common treatment-emergent adverse events (> or =2% of patients in any of the treatment groups) that occurred more frequently in the total paliperidone palmitate group versus the placebo group (with > or =1% difference) were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%). The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range (25, 100, or 150 mg eq.) in adult patients with acutely exacerbated schizophrenia.

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    ABSTRACT: Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotic, developed for monthly intramuscular (i.m.) administration into deltoid/gluteal muscle, approved for the treatment of schizophrenia in many countries. To assess the options for i.m. injection sites, dose-proportionality of PP was investigated after injection of a single dose (25–150 mg eq.) of PP in either gluteal (n = 106) or deltoid (n = 95) muscle of schizophrenic patients. Overall, mean (geometric) area under plasma concentration-time curve from time zero to infinity (AUC∞) of paliperidone increased proportionally with increasing PP doses, regardless of injection site. Mean maximum plasma concentration (Cmax) was slightly less than dose-proportional for both injection sites at PP doses >50 mg eq. Mean Cmax was higher after injection in the deltoid compared with the gluteal muscle, except for the 100 mg eq. dose, while AUC∞ for both injection sites was comparable at all doses. Median time to reach Cmax (tmax) ranged from 13–14 days after deltoid and 13–17 days after gluteal injection across all doses. Single PP injections in deltoid and gluteal muscles in the dose range of 25–150 mg eq. were generally tolerable both locally and systemically.
    The Journal of Clinical Pharmacology 03/2014; · 2.84 Impact Factor
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    ABSTRACT: Two thirds (66.7%) of patients with acute schizophrenia previously unsuccessfully treated with oral antipsychotics switched to flexibly dosed paliperidone palmitate (PP) achieved ≥ 30% improvement in symptom severity, measured by PANSS total score.•Significant improvements in PANSS total score from baseline were observed from Day 8 onwards; PANSS total score decreased significantly by a mean change of − 31.0 (± 29.0) from BL to EP.•PP was also associated with significant improvements in illness severity, subjective wellbeing and patient functioning.•No new safety signals were identified and PP was generally well tolerated.•The study design provides useful data on dosing and switching of PP in patients with acute schizophrenia, more closely resembling those encountered in clinical practice.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/2014; · 3.55 Impact Factor
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    ABSTRACT: Introduction: Several long-acting injectable (LAI) second-generation antipsychotics are now available for the management of schizophrenia. As patients with schizophrenia frequently present with diverse and challenging symptoms, it is important to understand the effects of antipsychotics in treating these different symptom subgroups and the timing of these responses. Areas covered: For this review, data from two randomized, double-blind trials were analyzed in respect to the onset and persistence of effects on several measures of psychopathology (as measured by the Positive and Negative Syndrome Scale [PANSS]) after treatment with LAI paliperidone palmitate (PP) (NCT00590577 and NCT00589914). Expert opinion: Symptom reductions from baseline with PP were significant by day 4 for all five PANSS factors in both studies. Some effects may have been driven by the presence or absence of a placebo response. A significant effect for PP versus placebo was observed for all major symptom domains for one or more doses of PP during the first month of treatment. Once established, most (but not all) significant responses persisted to the end point. Similar improvements were observed in PANSS scores with PP and oral risperidone. Dose-dependent trends were observed for the effect of PP on positive, negative and uncontrolled hostility/excitement symptoms.
    Expert Opinion on Pharmacotherapy 05/2014; 15(7):1029-42. · 2.86 Impact Factor

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