A Double-blind Study Of Paliperidone Palmitate And Risperidone Long-acting Injectable In Adults With Schizophrenia

Transcription

1 A Double-blind Study Of Paliperidone Palmitate And Risperidone Long-acting Injectable In Adults With Schizophrenia Gahan Pandina, Rosanne Lane, Srihari Gopal, Cristiana Gassmann-mayer, David Hough, Bart Remmerie, George Simpson Noor Naif Al-Hakami Clinical pharmacist intern 2014

2 The intramuscular (I.M.) long-acting injectable (LAI) formulations of antipsychotic medications were developed to enhance treatment adherence and improve the long-term management of schizophrenia Risperidone-LAI (RIS-LAI) was the first atypical antipsychotic available as an injectable formulation

3 Paliperidone palmitate (PP) is the palmitate ester of paliperidone the active metabolite of risperidone It is a once-monthly atypical antipsychotic LAI approved in the US for the acute and maintenance treatment of schizophrenia in adult Doses of mg eq. demonstrated efficacy and was generally safe and tolerable in previous double-blind, placebo-controlled studies in adult patients with schizophrenia

4 A study (Fleischhacker et al., 2009) compared efficacy of the two LAIs (risperidone and paliperidone) Adequate plasma levels of paliperidone were not achieved as a result of an inadequate initiation dosing regimen (initiated as gluteal injections of 50 mg eq. on days 1 and 8) Hence, It did not demonstrate noninferiority to RIS-LAI in that study

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6 To assess noninferiority of injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia

7 P I C O T Adults with schizophrenia Paliperidone palmitate LAI Risperidone LAI Noninferiority in safety and efficacy 13 week

8 This study was a randomized, double-blind, double-dummy, active-controlled, parallel-group, multicenter noninferiority comparative study conducted from March 2007 through July 2009 The study consisted of a screening period of up to 7 days for washout of disallowed psychotropic medications and for oral tolerability testing, followed by a 13-week double-blind treatment period

9 Eligible patients were randomly assigned (1:1) to either of two double-blind treatment groups: PP without oral supplementation OR RIS-LAI, with oral risperidone based on a computer-generated randomization scheme stratified by center, and implemented by an interactive voice response system A double-dummy design was used to preserve the blind because the two study drugs are different in appearance (syringe and needle sizes) The study drug administrator was the only person to contact IVRS to receive the patient's medication number

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11 Efficacy Safety pharmacokinetic The primary efficacy variable: The change in the PANSS (Positive And Negative Syndrome Scale) total score from baseline to the last post randomization assessment in the double-blind period Noninferiority was considered demonstrated if the primary efficacy variable was no worse in PP-treated patients than in RIS-LAI treated patients, by a protocol-specified noninferiority margin (i.e, 5 points in the change in PANSS total score)

12 Primary efficacy analysis Secondary efficacy analysis Per-protocol analysis Intent to treat analysis The primary efficacy variable (change in PANSS total score at endpoint) was analyzed using an analysis of covariance (ANCOVA) model

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19 QUESTIONS FOR APPRAISING

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24 In the current study, noninferiority of PP (50, 100, or 150 mg eq.;i.e. 78, 156, or 234 mg) without oral supplementation to RIS-LAI (25,37.5, 50 mg) with oral risperidone was established in treatment of schizophrenia using the approved (US) initiation dose strategy for PP Pharmacokinetic results were also similar between both treatments PP was generally safe and tolerable in these patients

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