Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study.
OBJECTIVE
We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia.


METHODS
Eligible patients (Positive and Negative Syndrome Scale [PANSS] total score < 120) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week, open-label phase. Patients received the first 2 intramuscular injections of paliperidone palmitate (50mg eq) one-week apart, then subsequent injections (25, 50, or 100mg eq, flexibly-dosed), once-monthly. Stable patients (PANSS total score < or = 75) continued into the 24-week maintenance phase. At maintenance phase endpoint, stabilized patients were randomized (1:1 ratio) to either continue paliperidone palmitate (at stabilized dose) or begin placebo in the variable-duration, double-blind phase.


RESULTS
The preplanned interim analysis (conducted after 68 relapse events) included 312 patients: mean age = 40 years, 55% men, 66% white, and mean transition baseline PANSS total score (SD): placebo, 69.5 (16.89); paliperidone palmitate, 69.3 (17.39). Time-to-relapse (primary endpoint) favored paliperidone palmitate (p<0.0001, log-rank test) at interim and final analysis (n=408). The hazard ratio (placebo/paliperidone palmitate) at the final analysis was 3.60 (95% CI: 2.45, 5.28). Treatment-emergent adverse event rates (final analysis set) were: 67% for transition and maintenance phases, and 45% (placebo) and 44% (paliperidone palmitate) for the double-blind phase. Across phases, the incidence of glucose-related adverse events was low (< or = 4%), while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients. Injection site tolerability was comparable between groups.


CONCLUSIONS
Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals.
Hough
David
D
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, New Jersey, USA. DHough2@its.jnj.com
Gopal
Srihari
S
Vijapurkar
Ujjwala
U
Lim
Pilar
P
Morozova
Margarita
M
Eerdekens
Mariëlle
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D010168:Palmitates / Q000008:administration & dosage*; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy*; D012720:Severity of Illness Index; D055815:Young Adult
D014150:Antipsychotic Agents; D007555:Isoxazoles; D010168:Palmitates; D011743:Pyrimidines; D000068882:Paliperidone Palmitate