A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia

Abstract

Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set (N=514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p< or =0.006) and PANSS negative and positive symptom Marder factor scores (p< or =0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5-6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia.

Figure 1

Study design. The doses expressed as paliperidone palmitate 25, 50, and 100 mg equiv. equate to 39, 78, and 156 mg, respectively, of paliperidone palmitate. One patient assigned to the paliperidone palmitate 25 mg equiv. group was excluded by the medical monitor on the day of randomization, due to hypotension, and hence did not receive any double-blind medication.

Figure 2

Kaplan–Meier estimates of time to withdrawal due to lack of efficacy (intent-to-treat analysis set). The doses expressed as paliperidone palmitate 25, 50, and 100 mg equiv. equate to 39, 78, and 156 mg, respectively, of paliperidone palmitate.

Figure 3

Onset of effect: least-squares mean change in PANSS total score over time (intent-to-treat analysis set). Mean (SD) changes in PANSS total scores from baseline to end point were −13.6 (21.45) for the 25-mg group, −13.2 (20.14) for the 50-mg group, and −16.1 (20.36) for the 100-mg equiv. group, vs −7.0 (20.07) for placebo. The mean (SD) values reported below the graph are absolute means and not adjusted for the covariates. The doses expressed as paliperidone palmitate 25, 50, and 100 mg equiv. equate to 39, 78, and 156 mg, respectively, of paliperidone palmitate. ^All unadjusted p-values <0.05 as early as day 36, for all three doses of paliperidone palmitate.

Figure 4

Treatment-emergent adverse events experienced by ⩾5% of patients in any treatment group. The doses expressed as paliperidone palmitate 25, 50, and 100 mg equiv. equate to 39, 78, and 156 mg, respectively, of paliperidone palmitate.