Effectiveness and Safety of Flexible Doses of Paliperidone Prolonged Release in Adolescent Patients With Schizophrenia

• A secondary endpoint will be the change from baseline in the PANSS total score at Week 26. [ Time Frame: Screening (Day -21 to Day -1), baseline (Day 1), Day 7, Day 14, Day 28, Day 56, Day 98, Day 140, Day 182 (end of study), or at early withdrawal ] [ Designated as safety issue: No ]
• A secondary endpoint will be the change from baseline in CGI-S score at Week 8 and Week 26. [ Time Frame: Baseline (Day 1), Day 7, Day 14, Day 28, Day 56, Day 98, Day 140, Day 182 (end of study), or at early withdrawal ] [ Designated as safety issue: No ]
• A secondary endpoint will be the change from baseline in Personal and Social Performance score at Week 8 and Week 26. [ Time Frame: Baseline (Day 1), Day 7, Day 14, Day 28, Day 56, Day 98, Day 140, Day 182 (end of study), or at early withdrawal ] [ Designated as safety issue: No ]
• A secondary endpoint will be the proportion of patients maintaining clinical stability at Week 26 (as measured from Week 8) based on PANSS total score and Clinical Global Impression Severity (CGI-S), suicidality or homicidal ideas, or hospitalization. [ Time Frame: Day 56 (Week 8), Day 98, Day 140, Day 182 (end of study), or at early withdrawal ] [ Designated as safety issue: No ]
• A secondary endpoint will be the change from baseline in the PANSS negative symptom factor score (based on Marder factor) at Week 8 and Week 26. [ Time Frame: Screening (Day -21 to Day -1), baseline (Day 1), Day 7, Day 14, Day 28, Day 56, Day 98, Day 140, Day 182 (end of study), or at early withdrawal ] [ Designated as safety issue: No ]

The primary objective of this study is to evaluate the efficacy of paliperidone prolonged release relative to another atypical antipsychotic, aripiprazole, in the treatment of symptoms of schizophrenia in adolescent patients (aged 12 to 17 years of age, inclusive)

This is a randomized (study drug is assigned by chance), double-blind (neither physician nor patient knows the name of the assigned drug), active-controlled (paliperidone prolonged relaease [PR] is compared to another drug used to treat the same condition), parallel-group, flexible-dose (the physician has the freedom to give different doses to the patient depending on how they respond to treatment), multicenter, study designed to determine the efficacy and safety of paliperidone PR in adolescents 12 to 17 years of age who have a Diagnostic and Statistical Manual of Mental Disorders; 4th Edition (DSM-IV) diagnosis of schizophrenia. The study seeks to evaluate the change in symptoms of schizophrenia in patients given paliperidone PR compared to patients given aripiprazole, as measured by a psychiatric rating scale, the Positive and Negative Syndrome Scale (PANSS). The change in PANSS total score from baseline to end point (Week 8 or, if the patient leaves the study early, the last time a measurement is made) will be measured. The study consists of 3 phases: an up-to-3-week screening phase (with a possible overlapping washout period to allow blood levels of other drugs being taken by the patient to decrease), an 8-week double blind acute phase, and an 18-week double-blind maintenance phase. The total duration of the study will be approximately 29 weeks. Patients will be randomly assigned to 1 of 2 treatment groups (paliperidone PR or aripiprazole flexible oral doses). Patients in the paliperidone PR group will receive 6 mg/day orally on Days 1 through 7. Patients in the aripiprazole group will receive 2 mg/day orally on Days 1 and 2, 5 mg/day on Days 3 and 4, and 10 mg/day on Days 5, 6, and 7. Beginning at Week 2 and throughout the treatment period, paliperidone PR may be flexibly dosed with 3 mg/day, 6 mg/day, or 9 mg/day; and aripiprazole may be flexibly dosed with 5 mg/day, 10 mg/day, or 15 mg/day. Adjustments to dose can occur at the scheduled visits.

• Drug: Aripiprazole
  Aripiprazole flexible doses in a range from 5 to 15 mg/day (2 mg/day on Days 1 and 2, 5 mg/day on Days 3 and 4, 10 mg/day on Days 5, 6, and 7, and flexible doses of 5, 10, or 15 mg/day thereafter)
• Drug: Paliperidone PR
  Paliperidone PR flexible doses in a range from 3 to 9 mg/day (6 mg/day from Day 1 to Day 7 and flexible doses of 3, 6, or 9 mg/day thereafter)

• Experimental: 001
  Paliperidone PR Paliperidone PR flexible doses in a range from 3 to 9 mg/day (6 mg/day from Day 1 to Day 7 and flexible doses of 3 6 or 9 mg/day thereafter)
  Intervention: Drug: Paliperidone PR
• Active Comparator: 002
  Aripiprazole Aripiprazole flexible doses in a range from 5 to 15 mg/day (2 mg/day on Days 1 and 2 5 mg/day on Days 3 and 4 10 mg/day on Days 5 6 and 7 and flexible doses of 5 10 or 15 mg/day thereafter)
  Intervention: Drug: Aripiprazole

Inclusion Criteria:

• Patients must currently meet the DSM-IV criteria for schizophrenia and have experienced symptoms of the illness for at least 1 year, and they should have had at least 1 treatment with an antipsychotic before participation in this study
• Patients must give assent to participate before screening procedures begin, and in countries where patients aged 12-17 years inclusive can give consent, the patient must sign the informed consent document
• Parent(s) or the legal guardian(s) of the patient must sign an informed consent document
• Patients must have a PANSS score between 60 and 120 inclusive at screening, and their physician must believe that the patient is not receiving optimal clinical benefit or is experiencing a problem with safety or tolerability of their current anti-psychotic medication
• Patients must be otherwise physically healthy
• Female patients must be incapable of pregnancy, or if heterosexually active and capable of pregnancy, have been using an acceptable method of contraception for at least 1 month before study entry and agree to continue use of 1 of these contraception methods for the duration of the study, or if sexually abstinent and capable of pregnancy, must agree to continue abstinence or to use an acceptable method of birth control should sexual activity commence
• Patients must not be a danger to themselves or others, and must have family support available to be maintained as outpatients
• Weight >29 kg

Exclusion Criteria:

• Patients who, at screening, meet the DSM-IV criteria for dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, or primary substance-induced psychotic disorder
• Patients with mild, moderate, or severe mental retardation
• History or presence of abnormalities of heart rhythm
• History of certain neurological disorders or insulin-dependent diabetes mellitus
• History of severe preexisting gastrointestinal narrowing or an inability to swallow oral study drug with the aid of water
• Patients who have received a depot injectable antipsychotic within 2 treatment cycles before the screening visit
• Clinically significant abnormalities in medical history, physical examination, electrocardiogram, or biochemistry, hematology, or urinalysis results, or evidence of clinically significant hepatic disease at screening
• Patients within their first psychotic episode
• Female patients who are pregnant, planning to become pregnant, or are nursing