Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3‐month formulation in patients with schizophrenia: A phase‐1, single‐dose, randomized, open‐label study

Abstract

This multicenter, randomized, open‐label, parallel‐group, phase‐1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3‐month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, aged 18–65 years) were enrolled in 1 of 4 separately conducted panels (A to D). Each panel had 2 single‐dose treatment periods (period 1, 1 mg intramuscular paliperidone immediate release [IR]; period 2, intramuscular PP3M 75−525 mg eq) separated by a washout of 7–21 days. Overall, 245 of 308 (79.5%) PP3M‐dosed patients completed the study. Because the PK studies of panels A and C were compromised by incomplete injection in some patients, PK data from only panels B and D are presented. Safety data from all panels are presented. Peak paliperidone plasma concentration was achieved between 23 and 34 days, and apparent half‐life was ∼2–4 months. Mean plasma AUC∞ and C max of paliperidone appeared to be dose‐proportional. Relative bioavailability in comparison with paliperidone was ∼100% independent of the dose and injection site. Headache and nasopharyngitis were the most common (>7%) treatment‐emergent adverse events. Overall, safety and tolerability were similar to those of the 1‐month formulation. Results support a once‐every‐3‐months dosing interval in patients with schizophrenia or schizoaffective disorder.