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

A Randomized, Double-Blind, Placebo-Controlled, Parellel-Group Study of Paliperidone Palmitate Evaluating Time to Relapse in Subjects With Schizoaffective Disorder

This study will evaluate the efficacy of paliperidone palmitate compared with placebo in the delay of relapse of the symptoms of schizoaffective disorder. This study will also assess the safety and tolerability of paliperidone palmitate in patients with 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.

Inclusion Criteria:

• DSM-IV diagnosis of schizoaffective disorder
• Experiencing an acute exacerbation of psychotic symptoms
• A score of >=4 on at least 3 of the following 7 PANSS items: Delusions (P1), Hallucinatory behavior (P3), Excitement (P4), Hostility (P7), Tension (G4), Uncooperativeness (G8), and Poor Impulse Control (G14)
• A score of >=16 on YMRS and/or a score of >=16 on the HAM-D-21
• Healthy based on physical examinations, electrocardiogram (ECG), laboratory tests, medical history, and vital signs measurements

Exclusion Criteria:

• A primary active mental illness diagnosis other than schizoaffective disorder
• Have attempted suicide within 12 months or are at imminent risk of suicide or violent behavior
• Subjects with first episode of psychosis
• Received electroconvulsive therapy in the past 3 months
• History of hypersensitivity to or intolerance of paliperidone, risperidone, or 20% Intralipid (placebo)
• Received long-acting antipsychotic medication within 2 injection cycles
• Received therapy with clozapine within 3 months
• A history of neuroleptic malignant syndrome
• Previous history of lack of response to antipsychotic medication
• Subjects receiving therapy with antidepressants or mood stabilizers that has been initiated and/or changed in dose <30 days prior to screening
• Receiving therapy with carbamazepine
• Receiving therapy with monoamine oxidase inhibitors
• Pregnant, breast-feeding, or planning to become pregnant