Clozapine/Paliperidone Versus Clozapine/Placebo in Resistant Schizophrenia
Condition: Schizophrenia; Schizophrenic Disorders; Psychotic Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      augmentation of clozapine with paliperidone in the treatment of resistant schizophrenia has
      not been tested until now in randomized controlled trials. This combination is supposed to
      have therapeutic efficacy in the treatment of resistant schizophrenia.
    

Detailed description: 
      This is a 12 weeks, blind study (the patient, investigator, and sponsor do not know the study
      drug and dosage being taken by the patient) of the safety and tolerability of flexible-dose
      (3 to 12mg per day), extended-release (ER) paliperidone in combination with clozapine with a
      diagnosis of schizophrenia. Patients who have completed study or who discontinued from that
      study because of lack of efficacy but completed a minimum of 21 days of the study may enter
      this study. This study consists of a 21-day screening and washout phase (to discontinue and
      "wash out" any medication not allowed in the study), and a double blind treatment phase of 12
      weeks, during which all patients will take oral paliperidone ER every day and clozapine
      versus clozapine alone, and a post-treatment phase consisting of a follow-up visit completed
      1 week after a patient has received the final dose of paliperidone ER. The study, including
      the screening and posttreatment phase, will last approximately 30 weeks. Screening and
      washout may be conducted while a patient is an outpatient. Safety will be assessed by
      laboratory measurements (chemistry, liver function tests, hematology, hormone, lipid
      assessments, prolactin [blinded], urinalysis, and urine drug screens; body weight, height,
      and waist circumference measurements; ECGs and the ESRS (extrapyramidal syndrome rating
      scale). These instruments will be used to assess extrapyramidal symptoms (EPS) and
      dyskinesias. Adverse events will be monitored including psychiatric adverse events of
      interest (worsening of psychosis, hyperprolactinemia, weight gain) that may be associated
      with paliperidone ER in this population. The primary aim of this study is to evaluate the
      long-term (12 weeks) safety and tolerability of clozapine/paliperidone ER in resistant
      schizophrenia. As exploratory secondary aims, the study will assess the effect of
      clozapine/paliperidone ER on the long-term symptoms of schizophrenia as measured by the
      changes in the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores, the
      global improvement in severity of illness as measured by the Clinical Global Impression(CGI)
      scale. Patients begin the study at 6.0 mg/day of oral paliperidone ER. If a higher dosage is
      needed, the dosage will be increased (in increments of 3 mg/day not more frequently than once
      every 5 days) to 12 mg/day. If the 6.0 mg/day dosage is not well tolerated, the dosage may be
      decreased (not more frequently than once every 5 days) to 3.0 mg/day. Patients will be dosed
      for up to 6 months.
    

Intervention name(s): paliperidone clozapine
Intervention type(s): Drug
Intervention description(s): dose 3 to 12 mg paliperidone ER daily during 12 weeks
Intervention MeSH terms: Paliperidone Palmitate; Clozapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment