Comparison of Paliperidone Palmitate and RISPERDAL CONSTA in Patients With Schizophrenia

• The Change From Baseline for the CGI-S Score [ Time Frame: Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks)] ] [ Designated as safety issue: No ]
  The CGI-S rating scale is used to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). This scale permits a global evaluation of the patient's condition at a given time. A qualified rater administered the CGI-S.
• The Change From Baseline in the PSP Score [ Time Frame: Baseline to the last postrandomization assessment in the double-blind treatment period (approximately 13 weeks) ] [ Designated as safety issue: No ]
  The PSP scale is used to assess the degree of dysfunction a patient exhibits over a 7-day period within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The results of the assessment are converted to a numeric score. A score between 71 and 100 indicates a mild degree of difficulty; a score between 31 and 70 indicates a moderate degree of dysfunction, and a patient with a score of 30 or less has functioning so poor he or she requires intensive supervision.

The purpose of this study is to demonstrate the effectiveness of paliperidone palmitate in patients with Schizophrenia.

This is a randomized (patients assigned to treatment groups by chance), double-blind (patient and study staff will not know the treatment assignment) study of paliperidone palmitate compared with RISPERDAL CONSTA (Risperidone Long-Acting Intramuscular Injection) in adult patients with schizophrenia. The total duration of the study will be approximately 14 weeks. For those patients without source documentation of tolerability to oral (by mouth) risperidone or paliperidone Extended Release (ER) tablets, injectable RISPERDAL CONSTA or paliperidone palmitate, or those patients who were not currently taking another antipsychotic, a minimum of 4 days and a maximum of 6 days of oral paliperidone ER treatment at a dosage of 6 mg/day will be administered for tolerability testing before the first injection of double-blind (DB) study drug (paliperidone palmitate or RISPERDAL CONSTA). During the DB period, study drug will be administered to patients as an intramuscular (i.m.) injection. Paliperidone palmitate (PP) 150mg equivalent (eq) (and RISPERDAL CONSTA placebo) at Baseline (BL) (Day 1), 100mg eq at Visit (V) 4 (Day 8), 50 or 100mg eq at V7 (Day 36), and 50,100,or 150mg eq at V9 (Day 64) or RISPERDAL CONSTA (RC) 25mg at V4 and V6 (Day 22), 25 or 37.5mg at V7, and 25, 37.5, or 50mg at V9 will be given as i.m. injections. Patients in the RC group will also take risperidone tablets (1-6 mg/day) at BL for 28 days and be given an injection of PP placebo at BL, V1, V7, and V9.

• Drug: RISPERDAL CONSTA
  RISPERDAL CONSTA: Type=exact number, unit=mg, number=25, 37.5, or 50, form=suspension for injection, route=Intramuscular use. One i.m. injection of RISPERDAL CONSTA 25-50 mg eq every 2 weeks at V4, V6, V7, V8, V9, and V10. PALIPERIDONE PALMITATE PLACEBO: Form=suspension for injection, route=Intramuscular use. One i.m. injection every 2 weeks at Baseline and at V4, V7, and V9. RISPERIDONE: Type=up to, unit=mg, number=1 to 6, form=Tablet, route=Oral Use. One tablet for the first 4 weeks (28 days) of the DB treatment period.
• Drug: Paliperidone palmitate
  PALIPERIDONE PALMITATE: Type=exact number, unit=mg, number=50, 100, or 150, form=suspension for injection, route=Intramuscular use. One i.m. injection of Paliperidone palmitate 50-150 mg eq every 4 wks at Baseline, V4, V7, and V9. RISPERDAL CONSTA PLACEBO: Form=suspension for injection, route=Intramuscular use. One i.m. injection every 4 weeks at Baseline, V4, V7, and V9.

• Active Comparator: RISPERDAL CONSTA
  RISPERDAL CONSTA 25-50 mg eq every 2 weeks
  Intervention: Drug: RISPERDAL CONSTA
• Experimental: R092670
  Paliperidone Palmitate 50-150 mg eq every 4 wks
  Intervention: Drug: Paliperidone palmitate

Inclusion Criteria:

• Meet diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria as specified by the protocol for at least 1 year before screening
• Prior medical records, written documentation or verbal information obtained from previous psychiatric providers obtained by the investigator must be consistent with the diagnosis of schizophrenia
• A total PANSS score between 60 and 120, inclusive, at screening and baseline; Body mass index (BMI) at the screening visit BMI at least 17 kg/m2
• Female patients must be postmenopausal for at least 2 years, surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before study entry and throughout the study as specified by the protocol. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (b hCG) pregnancy test result at screening.

Exclusion Criteria:

• Patient unable to provide consent or involuntarily committed to psychiatric hospitalization; A primary, active DSM-IV diagnosis on Axis I other than schizophrenia
• A DSM-IV diagnosis of active substance dependence within 3 months before screening (nicotine and caffeine are not exclusionary)
• History of treatment resistance as defined by failure to respond to 2 adequate treatments with different antipsychotic medications (an adequate treatment is defined as a minimum of 6 weeks at maximum tolerated dosage)
• Relevant history or current presence of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular disease), renal, hepatic, hematologic, endocrine, immunologic, or other systemic disease including history of neuroleptic malignant syndrome; History of any severe pre-existing gastrointestinal narrowing or inability to swallow oral study drug whole with the aid of water (applies to those patients requiring oral tolerability only)
• Significant risk of suicidal or violent behavior, as clinically assessed by the investigator ; History of life-threatening allergic reaction to any drug; Known or suspected hypersensitivity or intolerance to risperidone, paliperidone, 20% Intralipid, or any of their excipients (e.g., soybean oil, egg yolks, phospholipids, and glycerol)
• Have received an experimental drug or experimental biologic, or used an experimental medical device within 6 months before screening; History of any active malignancy within the previous 5 years, with the exception of basal cell carcinomas
• Women who are pregnant or breast-feeding or are planning to become pregnant uring the study