A Safety, Tolerability, and Treatment Response Study of Paliperidone Palmitate Administered to Patients With Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of the study is to evaluate the safety, tolerability and treatment response of
      paliperidone palmitate administered as once-monthly injections to patients with
      schizophrenia.
    

Detailed description: 
      This study is an 18-month, single-group, open-label (name of study drug is known to
      patients), multicenter study to evaluate the safety, tolerability and treatment response of
      paliperidone palmitate administered as once-monthly injections to patients with schizophrenia
      who previously received treatment with oral antipsychotic medications. A target of 587
      patients (inpatients or outpatients) with schizophrenia will be enrolled in the study and
      will receive, without cost, injections of study drug (paliperidone palmitate) on Days 1, 8,
      38, and thereafter at one-month intervals up to 18 months. Enrollment in the study will be
      limited to patients who are diagnosed with schizophrenia within the past 5 years. The study
      will consist of a screening period of up to 5 days before treatment, an 18-month treatment
      period, and an end-of-study or early withdrawal visit approximately 30 days after the last
      injection of study drug. During the screening period (after patients have provided signed
      informed consent to participate in the study), information will be collected regarding the
      patients medical and psychiatric history, demographics (age and race), current symptoms of
      the patients schizophrenia, and whether or not the patient would like to sign an additional
      informed consent form to participate in the pharmacogenomic (the study of how genes affect a
      person's response to drugs) component of the study that involves the collection of one 10 ml
      blood sample (equivalent to about 2 teaspoons of blood). During screening, entry criteria for
      the study will be reviewed and a physical examination performed. Patients will also be asked
      questions about the types of healthcare resources (institutionalizations/hospitalizations,
      emergency room visits, etc) they utilized during the previous 12 months however, this
      information is optional and its collection will depend upon the availability of the data.
      Patients who are currently receiving treatment with any oral antipsychotic medication must
      discontinue the use of the medication by Day 1 of the study. If the patient was receiving a
      high dose of an antipsychotic medication or was also receiving an anticholinergic medication
      (a drug that prevents involuntary muscle movements associated with the use of antipsychotic
      drugs in the treatment of schizophrenia), the investigator may decide to have the patients
      dose of antipsychotic (and/or anticholinergic) medication tapered (gradually reduced) to
      discontinuation beginning on Day 1. The patients time to taper-off the previous antipsychotic
      and/or anticholinergic medications will depend on the dose of the medication. Patients
      receiving anxiolytics (anti-anxiety drugs), mood stabilizers, anticholinergics, or
      antidepressants greater than 4 weeks before the screening visit will be allowed to continue
      taking these drugs. Upon meeting the entry criteria for the study, patients will receive a
      total of 19 intramuscular (IM) injections of paliperidone palmitate during the 18-month
      treatment period as follows: 150 mg equivalent (eq) on Day 1, 100 mg eq on Day 8, 75 mg eq on
      Day 38, and paliperidone palmitate injections of 50, 75, 100, or 150 mg eq once monthly on
      Days 68, 98, 128, 158, 188, 218, 248, 278, 308, 338, 368, 398, 428, 458, 488 and 518.
      Depending on the patients ability to tolerate a dose paliperidone palmitate, doses may be
      adjusted higher or lower every 30 days per the clinicians judgment within the dose range of
      50 to 150 mg eq. If the patient reports any signs or symptoms of worsening of schizophrenia,
      the investigator may prescribe a rescue medication (quick-relief or fast-acting medications
      that usually work right away to relieve symptoms) such as lorazepam (an antianxiety drug) to
      control agitation, irritability, restlessness, and hostility. The investigator may also
      prescribe an anticholinergic medication to treat involuntary movement disorders if observed
      in patients. All prescription and over-the-counter medications taken by patients during the
      study are to be reported. At the end of the 18-month treatment period, all patients will
      complete an end-of-study visit (or early withdrawal visit for patients who do not complete
      the study) to have a physical examination performed, laboratory tests (including a urine
      pregnancy test for women of childbearing potential) performed, vital signs measured, and
      information collected regarding the occurrence of adverse events and the use of medications
      other than study drug from the time of the previous study visit to the end-of-study (or early
      withdrawal visit). The primary objective of the study is to evaluate safety, tolerability and
      treatment response of once-monthly injections of paliperidone palmitate measured by the use
      of a Positive And Negative Symptom Scale (PANSS). The safety and tolerability of once-monthly
      injections of paliperidone palmitate administered to patients with schizophrenia will be
      evaluated during the study by monitoring adverse events, findings from clinical laboratory
      tests (serum chemistry including lipids), vital sign measurements (blood pressure, pulse
      rate, and weight), physical examinations, and movement disorder evaluations using the
      Extrapyramidal Symptom Rating Scale [ESRS-A]). All clinically significant abnormalities in
      patients that persist at the end of the study will be followed by the Investigator until
      resolution or until a clinically stable endpoint is reached. Treatment response will be
      evaluated 5 times during the study (Visits 2, 4, 6, 8 and 10) by findings obtained from the
      PANSS (a 30-item questionnaire that is administered to the patient by a qualified person [ie,
      rater] to measure the presence/absence and severity of positive and negative symptoms of
      schizophrenia. In addition to the safety, tolerability, and treatment response data
      collected, patients who volunteer to participate in the pharmacogenomic component of the
      study will have one 10 ml sample of blood collected at on Days of Visit 2. If a replacement
      blood sample is needed for the pharmacogenomic component of the study, the patient will need
      to sign an additional informed consent form. Patients will receive a paliperidone palmitate
      intramuscular (IM) injection of 150 mg equivalent (eq) on Day 1, 100 mg eq on Day 8, and 75
      mg eq on Day 38.Thereafter, patients will receive once monthly IM injections of 50, 75, 100,
      or 150 mg eq of paliperidone palmitate. Doses may be adjusted every 30 days per the
      clinician's judgment within the dose range of 50 to 150 mg eq.Patients will receive a total
      of 19 injections of study drug over an 18-month treatment period.
    

Intervention name(s): Paliperidone palmitate
Intervention type(s): Drug
Intervention description(s): One intramuscular (IM) injection of paliperidone palmitate 150 mg equivalent (eq.) on Day 1, 100 mg eq. on Day 8, and 75 mg eq. on Day 38. Thereafter, one IM injection of paliperidone palmitate 50, 75, 100, or 150 mg eq. once monthly. Doses may be adjusted every 30 days per the clinician's judgment within the dose range of 50 to 150 mg eq.
Intervention MeSH terms: Paliperidone Palmitate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Schizophrenia; R092670; Paliperidone palmitate; Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; Intramuscular injection