A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia

This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N=1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150mgeq.), day 8 (100mgeq.), and once-monthly flexible dosing as deltoid or gluteal injections on day 36 (50mgeq. or 100mgeq.) and day 64 (50mgeq. or 100mgeq. or 150mgeq.) or b) RIS-LAI: gluteal injections days 8 and 22 (25mg), days 36, 50 (25 or 37.5mg) and days 64, 78 (25, 37.5 or 50mg). RIS-LAI-treated patients received oral supplementation with RIS 1–6mg/day (days 1 to 28), and PP-treated patients received oral placebo. The safety analysis set (n=1214) included 58% men, 78% white, with mean (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28). Mean (SD) change from baseline to endpoint in PANSS total score decreased similarly in both groups; PP (−18.6 [15.45]) and RIS-LAI (−17.9 [14.24]). PP treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [−1.62;2.38], per-protocol analysis set [primary analysis]). The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings. ►Paliperidone palmitate was demonstrated to be noninferior to risperidone long-acting injectable in treatment of schizophrenia using the approved initiation dose strategy. ►Paliperidone palmitate was generally safe and tolerable. ►Pharmacokinetic results were similar between both treatments.