Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study

Abstract

We evaluated the efficacy and safety of the investigational long-acting injectable antipsychotic agent paliperidone palmitate (PP) in the treatment of schizophrenia. Patients were randomized to receive gluteal injections of placebo or PP (50 or 100 mg eq., fixed doses), without oral supplementation, on days 1, 8, and 36 (9-wk, double-blind phase) in this phase 2b study. Patients (n=197, intent-to-treat analysis set) were 62% men, mean (s.d.) age 39 (10) yr, with a baseline mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total score of 87.0 (12.5). Mean (s.d.) PANSS total scores showed significant improvement at endpoint (primary measure) for both the PP 50 mg eq. [-5.2 (21.5)] and PP 100 mg eq. [-7.8 (19.4)] groups, vs. placebo [6.2 (18.3)] (p0.001, each dose vs. placebo). This improvement was detected by day 8 and maintained to endpoint (p0.011) for both doses. In the safety analysis set (n=247), fewer PP-treated patients (2%) discontinued for treatment-emergent adverse events vs. placebo-treated (10%). Rates of treatment-emergent extrapyramidal syndrome-related adverse events were comparable between active treatment and placebo, with the exception of parkinsonism-related disorders (50 mg eq. 5%, 100 mg eq. 8%, placebo 1%). Results of other safety measures suggest PP to be generally well-tolerated. Throughout the study, investigators rated injection-site pain as absent (56-71%), mild (24-39%), moderate (2-12%), or severe (0-2%). PP (50 and 100 mg eq. doses) administered as a gluteal intramuscular injection was efficacious and generally tolerated in these patients with acute symptomatic schizophrenia.

Onset and persistence of efficacy by symptom domain with long-acting injectable paliperidone palmitate in patients with schizophrenia

“…In short-term studies, PP LAI given according to the dosing schedule provided sustained plasma concentrations and documented improvement in clinical outcomes, such as a reduction in symptoms of schizophrenia, with an efficacy and safety profile similar to flexibly dosed risperidone long-acting injection (RLAI) [10,11,[38][39][40][41]. The AEs of PP were similar to those of oral paliperidone, oral risperidone and RLAI [10,11].…”

Development and Characterization of Thermosensitive intranasal Gel Containing Paliperidone Loaded Microspheres

“…(weight of microspheres Percentage yield 100 weight of polymer drug (1) Particle size analysis 16 Particle size of the microspheres was determined by optical microscopy. The eye piece micrometer was calibrated with the help of a stage micrometer.…”

“…Paliperidone palmitate (PP) has been shown to be an effective and tolerated second generation antipsychotic agent, especially in the treatment of schizophrenia. 1 Paliperidone works by inhibiting serotonergic type 2 receptors (5-HT2A) and dopamine type 2 receptors (D2). [2][3][4] Paliparidone belongs to BCS class II and has limited oral bioavailability.…”

Paliperidon palmitata bağlı gelişen siyah kıllı dil

“…Bunun yanında α1 ve α2 adrenerjik reseptör ve H1 reseptör antagonizması bulunur. Neredeyse hiç kolinerjik reseptör afinitesi bulunmaz 4 . Aylık enjeksiyon şeklinde yapılan bu ilacın yarı ömrü 25-49 gündür 5 .…”