Paliperidone palmitate is an investigational, injectable atypical antipsychotic. The safety and tolerability of initiating treatment with paliperidone palmitate via deltoid versus gluteal injections given once monthly, and of switching injection sites, in adults with stable schizophrenia were assessed. In this crossover trial, stable outpatients (N=252) were randomly assigned 1:1:1 to 3 dose groups (paliperidone palmitate 50, 75, or 100 mg eq.) and 2 treatment sequences (blinded to dose): deltoid muscle (period 1 [13 weeks]) followed by gluteal muscle (period 2 [12 weeks]) or the reverse. The intent-to-treat analysis set had 249 patients: mean age=43 (SD: 12.8) years; 57% men, 81% white, baseline mean Positive and Negative Syndrome Scale (PANSS) total score=56 (SD: 11.5). A total of 170 (68%) patients completed the study, with a similar proportion completing each treatment sequence. The incidence of systemic treatment-emergent adverse events (TEAEs) was similar between the 2 injection sites across doses during period 1 (deltoid [D]: 61% to 67%; gluteus [G]: 58% to 65%), and during the last 8 weeks of the 2 study periods (DG: 32% to 45% [period 1], 29% to 42% [period 2]; GD: 31% to 40% [period 1], 30% to 41% [period 2]). During the first treatment week, median plasma paliperidone concentrations were higher with treatment initiation in the deltoid muscle compared with the gluteal muscle. At apparent steady state, there was little difference in plasma paliperidone concentrations between the deltoid and gluteus sites for a given dose. Local tolerability was slightly better with gluteal injections. Patient preference for injection sites differed between geographical regions, e.g. patients from the US preferred deltoid to gluteal sites. The most common (>or=5% overall) TEAEs were: (period 1) insomnia, anxiety, headache, and agitation; and (period 2) insomnia, psychotic disorder, weight increased, and tachycardia. Paliperidone palmitate treatment was tolerated, irrespective of injection site, and thus could offer the choice of administration into either the deltoid or gluteal muscle to meet patient and physician preference.
Trial registration: ClinicalTrials.gov NCT00119756.