A Study to Evaluate the Efficacy of Paliperidone Palmitate in the Prevention of Relapse of the Symptoms of Schizoaffective Disorder

Schizoaffective disorder is a chronic illness and generally requires life-long treatment. To
date however, no medication has been evaluated in the maintenance treatment of
schizoaffective disorder. This is a randomized (study drug assigned by chance), double-blind
(neither physician nor patient knows the name of the assigned drug), placebo-controlled,
parallel-group, multicenter study to evaluate the efficacy and safety of paliperidone
palmitate, as monotherapy or as an adjunct to mood stabilizers or antidepressants, relative
to placebo in delaying the time to relapse in patients with schizoaffective disorder. This
study explores the use of paliperidone palmitate either as monotherapy or as an adjunct to
mood stabilizers or antidepressants (MS/AD) because both treatment approaches are commonly
used in the clinical management of schizoaffective disorder. Patients with acute symptoms of
schizoaffective disorder will be enrolled. The study will consist of 4 periods: an up to 7
days screening/tolerability period, a 13-week open-label flexible dose lead-in period, a
12-week open-label fixed dose stabilization period, and a 15 months double-blind relapse
prevention period. Patients without previous exposure to paliperidone ER (Invega),
paliperidone palmitate (Invega Sustenna), risperidone, or RISPERDAL CONSTA will be given 4
to 6 days of paliperidone ER 6mg/day for tolerability testing. Patients can continue their
current antipsychotic regimen through Day -1 (the day before the start of the study period).
During the open-label periods, all patients will be treated with paliperidone palmitate. An
initial loading dose of 234 mg (150 mg eq.) of paliperidone palmitate will be given by
deltoid injection followed by 156 mg (100 mg eq.) deltoid injection on Day 8. Starting on
Day 36, injections may be administered in either the deltoid muscle or the gluteal muscle.
Doses at Days 36, 64 and 92 may be increased or decreased within the range of 78 mg (50 mg
eq.) and 234 mg (150 mg. eq.) as clinically indicated. Dose will be fixed (at Day 92 dose)
during the 12-week stabilization period. Patients who meet pre-determined stabilization
criteria will be eligible to enter the double-blind relapse prevention period and will be
randomly assigned to either receive paliperidone palmitate (at the Day 92 dose) or placebo
treatment. Patients will have intramuscular (i.m.) study drug injection and efficay and
saftety evaluations performed every 4 weeks throughout the study. Efficacy will be evaluated
during the study using a relapse assessment, the Positive and Negative Symptom Scale
(PANSS), the Clinical Global Impression of Severity for Schizoaffective Disorder
(CGI-S-SCA), the Personal and Social Performance Scale (PSP), the Young Mania Rating Scale
(YMRS), and the Hamilton Rating Scale for Depression (HAM-D). Safety will be assessed
throughout the study by monitoring of adverse events, clinical laboratory tests,
electrocardiograms (ECGs), vital sign measurements (temperature, pulse, and blood pressure),
weight, and the monitoring of extrapyramidal symptoms using the Extrapyramidal Symptom
Rating Scale-Abbreviated (ESRS-A). Suicidality will be assessed by the Columbia Suicide
Severity Rating Scale (C-SSRS). A 10 milliliter pharmacogenomic blood sample (sample for DNA
research) will be collected from patients who give separate written informed consent for
this part of the study. Participation in pharmacogenomic research is optional. Blood samples
will be taken from patients being treated with lithium or valproate for the measurement of
blood lithium or valproate levels. Approximately 52 mL (31 mL for patients who are not
receiving lithium or valproate) of whole blood will be collected during the study. All
patients will receive paliperidone palmitate 78, 117, 156, 234 mg (50, 75, 100, or 150 mg
eq.) monthly by i.m. injection for the the first 25 weeks of the study (open-label periods).
During the 15-month double-blind relapse prevention period, one half of the patients will be
randomized to paliperidone palmitate treatment (50, 75, 100, or 150 mg eq. monthly i.m.
injection) and the other half of the patients will be randomized to monthly placebo
injection.