Study of Paliperidone Palmitate 3 Month and 1 Month Formulations for the Treatment of Patients With Schizophrenia

• The changes from baseline in the neuropsychiatric symptoms of schizophrenia using the Positive and Negative Syndrome Scale (PANSS) during the Double-blind Phase. [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
  The PANSS scale provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items). Each item is rated 1 (absent) to 7 (extreme).
• The changes from baseline in the patient's overall clinical condition measured by the change in Clinical Global Impression Severity (CGI-S) scale during the Double-blind Phase. [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
  The CGI-S rating scale is used to rate the severity of a patient's overall clinical condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe).
• The changes from baseline in the patient's functional status, measured by the Personal and Social Performance (PSP) scale during the Double-blind Phase. [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
  The PSP scale measures personal and social functioning in the domains of: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior.
• The proportion of patients who meet criteria for symptomatic remission. [ Time Frame: Week 41 to 65 ] [ Designated as safety issue: No ]
  The proportion of patients with a simultaneous score of mild or less on all selected PANSS items (P1, P2, P3, N1, N4, N6, G5, and G9) maintained from Visit 14 (Week 41) to the end of the Double-blind Phase (Week 65).

The purpose of this study is to demonstrate that a paliperidone palmitate 3 month formulation (PP3M) is as effective as the paliperidone palmitate 1 month formulation (PP1M) in the treatment of patients with schizophrenia who have been stabilized on PP1M.

This is a randomized (the study drug is assigned by chance), double blind (neither physician nor patient knows the treatment that the patient receives), parallel group (each group of patients will be treated at the same time), multicenter non-inferiority (the effect of the new treatment is not worse than that of the comparison treatment) study. The study consists of 3 phases: a screening/washout/tolerability phase (up to 21 days); a 17-week open-label (all people know the identity of the intervention) stabilization phase (referred to as the Open-label Phase) and a 48-week fixed dose, randomized, double-blind controlled phase (referred to as the Double-blind Phase). After completion of the Screening Phase, all patients will receive PP1M in the Open-label Phase. During this time, flexible dosing will occur at Weeks 5 and 9. At Week 13 patients are to receive the dose of PP1M that was administered at Week 9. Patients who are clinically stable at the end of the Open-label Phase will enter the Double-blind Phase and will be randomly assigned in a 1:1 ratio to receive fixed doses of PP3M or PP1M.

• Drug: PP3M 175 mg eq.
  Type= exact number, unit= mg eq., number= 175, form= injection, route= intramuscular use. One injection every third month for 48 weeks.
• Drug: PP3M 263 mg eq.
  Type= exact number, unit= mg eq., number= 263, form= injection, route= intramuscular use. One injection every third month for 48 weeks.
• Drug: PP3M 350 mg eq.
  Type= exact number, unit= mg eq., number= 350, form= injection, route= intramuscular use. One injection every third month for 48 weeks.
• Drug: PP3M 525 mg eq.
  Type= exact number, unit= mg eq., number= 525, form= injection, route= intramuscular use. One injection every third month for 48 weeks.
• Drug: Placebo (20% Intralipid)
  Form= injection, route= intramuscular use. One injection monthly when not receiving active medication for 48 weeks.
• Drug: PP1M 50 mg eq.
  Type= exact number, unit= mg eq., number= 50, form= injection, route= intramuscular use. One injection every month for 48 weeks.
• Drug: PP1M 75 mg eq.
  Type= exact number, unit= mg eq., number= 75, form= injection, route= intramuscular use. One injection every month for 48 weeks.
• Drug: PP1M 100 mg eq.
  Type= exact number, unit= mg eq., number= 100, form= injection, route= intramuscular use. One injection every month for 48 weeks.
• Drug: PP1M 150 mg eq.
  Type= exact number, unit= mg eq., number= 150, form= injection, route= intramuscular use. One injection every month for 48 weeks.

• Experimental: Paliperidone palmitate 3-month (PP3M)
  Interventions:

  • Drug: PP3M 175 mg eq.
  • Drug: PP3M 263 mg eq.
  • Drug: PP3M 350 mg eq.
  • Drug: PP3M 525 mg eq.
  • Drug: Placebo (20% Intralipid)
• Active Comparator: Paliperidone palmitate 1-month (PP1M)
  Interventions:

  • Drug: PP1M 50 mg eq.
  • Drug: PP1M 75 mg eq.
  • Drug: PP1M 100 mg eq.
  • Drug: PP1M 150 mg eq.

Inclusion Criteria:

• Patients with schizophrenia for more than 1 year and whose symptoms are worsening in the opinion of the investigator
• A total score in the Positive and Negative Syndrome Scale (PANSS) between 70 and 120
• Signed informed consent
• Women must not be pregnant, breastfeeding, and if capable of pregnancy must practice an effective method of birth control
• Men must agree to use a double-barrier method of birth control
• Be medically stable on the basis of clinical laboratory tests, physical examination, medical history, vital signs, and electrocardiogram (ECG)

Exclusion Criteria:

• A diagnosis other than schizophrenia, e.g., dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, primary substance-induced psychotic disorder, dementia-related psychosis
• Relevant history or current presence of any significant or unstable medical condition(s) determined to be clinically significant by the Investigator (ie, obesity, diabetes, heart disease etc)
• A diagnosis of substance dependence within 6 months before screening
• History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia
• Clozapine use in the last 2 months when used for treatment-resistant or treatment-refractory illness
• Clinically significant findings in biochemistry, hematology, ECG or urinalysis results
• Any other disease or condition that, in the opinion of the investigator, would make participation not in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments