Prevention of Relapse With Oral Antipsychotics Versus Injectable Paliperidone Palmitate (PROSIPAL)

• The primary outcome measure is time to a relapse event. [ Time Frame: Relapse is assessed from baseline (Day 1) up to maximally 24 months. ] [ Designated as safety issue: No ]
  

• The percentage of treatment responders defined as achieving > or = 30% improvement in PANSS total score at endpoint versus baseline [ Time Frame: every visit: screening, day 1, 8, 38, 68, 98, 128, 158, 188, 278, 368, 458, 548, 638, 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  
• Changes from baseline in total PANSS score and PANSS sub-domains/symptom factors [ Time Frame: every visit: screening, day 1, 8, 38, 68, 98, 128, 158, 188, 278, 368, 458, 548, 638, 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  
• Changes from baseline in level of functioning (PSP) [ Time Frame: screening visit, days 1, 38, 68, 98, 188, 278 368 458 548 638 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  
• Overall score and changes from baseline in global severity of illness (CGI-S, CGI C) [ Time Frame: every visit: screening, day 1, 8, 38, 68, 98, 128, 158, 188, 278, 368, 458, 548, 638, 728 and at withdrawal or relapse ] [ Designated as safety issue: No ]
  
• Measures of patient's mental health, well-being, treatment satisfaction and physician treatment satisfaction [ Time Frame: days 1, 188, 368 and 728 and at early withdrawal and relapse ] [ Designated as safety issue: No ]
  

This is a randomized (study drug assigned by chance), open-label (both physician and patient know the name of the assigned drug), rater-blinded (the person who assesses the condition of the patient does not know the name of the assigned drug), active-controlled, parallel-group, multicenter, prospective international study of paliperidone palmitate versus treatment as usual with oral antipsychotic agents in monotherapy in the prevention of relapse (return of symptoms). Patients who have been recently diagnosed with schizophrenia (within 5 years) and are suffering from a schizophrenic relapse (return of symptoms of schizophrenia) will be enrolled. This study consists of a 2-week initial acute oral treatment phase, followed by a treatment phase until relapse or up to maximally 24 months, whichever comes first. Prior to a 2-week oral treatment phase, patients will be randomly (by chance) assigned in a 1:1 ratio to receive treatment with paliperidone palmitate injection (once-monthly) or oral antipsychotic medication (daily). Patients randomized to paliperidone palmitate will first receive oral paliperidone ER once daily for 2 weeks followed by paliperidone palmitate injections at a dose of 150 mg eq. on Day 1, 100 mg eq. on Day 8 and 75 mg eq. on Day 38 and doses in a dose range of 25 to 150 mg eq. in either the deltoid or the gluteal muscle thereafter. Patients randomized to oral comparator arm will receive oral antipsychotics (haloperidol, paliperidone ER, risperidone, olanzapine, quetiapine and aripiprazole) as per investigator discretion and prescribed according to the label. Total treatment duration is maximally 24 months. During the 24 month treatment phase, investigators will be allowed to flexibly decrease or increase the dose of paliperidone palmitate with one dose level in the range of 25 to 150 mg eq. or the oral antipsychotic in the respective locally approved dose range, all according to the patient's clinical needs. The primary endpoint of the 24-month treatment phase will be the time to relapse. Safety will be monitored by evaluating Adverse Events (AEs), rating of extrapyramidal symptoms (symptoms like abnormal muscle movements, abnormal movements of the tongue or jaw, slow or sustained muscle contractions, muscle spasms, shaking, abnormal movements of the eyes, involuntary muscle contractions, slow movements, or restlessness), vital signs measurements (including heart rate and blood pressure), body weight and physical examination findings. A urine pregnancy test will be performed in females of childbearing potential. Adverse events (unintended, but not necessarily unexpected, results of therapy that can be unpleasant or dangerous), associated concomitant medications, and symptoms of relapse will be recorded as needed. Patients randomized to paliperidone palmitate will first receive oral paliperidone ER once daily for 2 weeks followed by paliperidone palmitate injections at a dose of 150 mg eq. on Day 1, 100 mg eq. on Day 8 and 75 mg eq. on Day 38 and doses in a dose range of 25 to 150 mg eq. in either the deltoid or the gluteal muscle thereafter. Patients randomized to oral medications will be treated daily with the prescribed drug according to the label. Total treatment duration is maximally 24 months.