title: 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 Cmax 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.
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Paulien
authors.initials: P
authors.lastname: Ravenstijn
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Remmerie
authors.affiliation: Janssen Research & Development, Titusville, NJ, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Savitz
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Mahesh N
authors.initials: MN
authors.lastname: Samtani
authors.affiliation: Janssen Research & Development, Titusville, NJ, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Nuamah
authors.affiliation: Janssen Research & Development, Raritan, NJ, USA.
authors.forename: Cheng-Tao
authors.initials: CT
authors.lastname: Chang
authors.affiliation: Janssen Research & Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: De Meulder
authors.affiliation: Janssen Research & Development, Titusville, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hough
authors.affiliation: Janssen Research & Development, Titusville, NJ, USA.
authors.forename: Srihari
authors.initials: S
authors.lastname: Gopal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011618:Psychotic Disorders / Q000188:drug therapy; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D000068882:Paliperidone Palmitate
keywords: long-acting injectable; paliperidone palmitate 3-month (PP3M); pharmacokinetics; safety; schizophrenia