A Double-blind, Placebo-controlled Study of the Safety and Efficacy of Paliperidone Extended Release (ER) in the Treatment of Schizophrenia in Adolescent Patients
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the efficacy, safety, and tolerability of 3
      weight-based, fixed-dose groups of paliperidone extended release (ER) compared with placebo
      in adolescent patients between 12 to 17 years of age, who are diagnosed with schizophrenia.
      Paliperidone ER is an atypical antipsychotic agent approved by the U.S. Food and Drug
      Administration for the treatment of schizophrenia in adults. Patients may be voluntary
      inpatients or outpatients at the time of the screening visit, but should have returned to
      their usual living situation by Day 21 of the double-blind treatment phase. The study
      duration is approximately 10 weeks. Patients who have completed this study or who were
      discontinued from this study due to lack of efficacy but have completed at least 21 days of
      double-blind treatment and are expected to benefit from paliperidone treatment, may enter an
      optional open-label safety study.
    

Detailed description: 
      The study is a multicenter, randomized (treatment group is assigned by chance), double-blind
      (neither the physician nor the patient knows which treatment group the patient is in),
      parallel-group, placebo controlled study. This study will enroll adolescent men and women who
      have schizophrenia as specified by the Diagnostic and Statistical Manual of Mental Disorders;
      4th Edition (DSM-IV) diagnosis of schizophrenia (295.10, 295.20, 295.30, 295.60, and 295.90)
      as confirmed by the Kiddie-Sads-Present and Lifetime Version (KSADS-PL), and who should have
      a Positive and Negative Syndrome Scale (PANSS) score that is between 60 and 120, inclusive,
      at screening and baseline. Before any study related procedure is performed, the patient and
      his parent or legal guardian must have provided assent and signed an informed consent form,
      respectively. The study consists of 3 phases: a screening phase, a 6-week double-blind
      treatment phase with an end-of-study or early withdrawal visit, and a 1 week follow-up visit
      for patients who do not enter the optional open-label safety study. In the screening phase, a
      trained clinician will complete the K SADS-PL interview, including all 5 supplements, to
      confirm the DSM-IV diagnostic criteria for schizophrenia. In addition, the K-SADS-PL
      screening diagnostic interview items for suicide must each have a score of <=2, as follows:
      item a), recurrent thoughts of death; item b), suicidal thoughts; item c), suicide attempts
      and their seriousness; item d), suicide attempts and their lethality; and item e) self
      harming behavior. Women of childbearing potential will undergo a urine pregnancy test at
      screening, baseline, Week 4, and at end of study or upon early withdrawal from the study.
      Patients who are receiving prohibited medications, such as antidepressants, lithium, drugs of
      abuse, and alcohol, will enter a washout period during which medications will be tapered down
      and eventually stopped. The screening and washout phase may not exceed 21 days. In the
      double-blind treatment phase, at the baseline visit, the inclusion and exclusion criteria
      will be reviewed. Patients who continue to meet the criteria will be randomly assigned (as in
      the toss of a coin) to 1 of 4 dose groups. Patients weighing between 29 to <51 kilograms (kg)
      will receive paliperidone ER 1.5, 3.0, or 6.0 milligrams (mg) or matching placebo. Patients
      weighing >=51 kg will receive paliperidone ER 1.5, 6.0, or 12.0 mg or matching placebo.
      Patients will come to the study site for weekly visits during this phase. A follow-up visit
      will occur 1 week after the end of treatment for those patients who will not enter the
      open-label study. Efficacy and safety procedures will be performed at specified times during
      the study. Efficacy procedures include the administration of the PANSS, Children's Global
      Assessment (CGAS), Clinical Global Impression-Severity (CGI-S) and a sleep visual analog
      scale. Safety assessments include a physical examination (ECG measurements, vital signs,
      weight, height, and waist measurements), clinical laboratory testing, drug screen, Simpson
      and Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement
      Scale (AIMS), Tanner Staging, concomitant medications and the recording of adverse events. A
      Data Safety Monitoring Board will oversee the conduct of the study and review adverse event
      reports and laboratory test results. The total volume of blood drawn for laboratory
      evaluation throughout the study, including 10 milliliters (mL) for the optional
      pharmacogenomics testing, is approximately 66 mL for each patient. Blood samples will be
      collected to explore the pharmacokinetics of paliperidone in adolescent patients. The study
      hypothesis is that at least 1 paliperidone ER dose group will be superior to placebo in
      improving the symptoms of schizophrenia as measured by the change in total PANSS score from
      the baseline to endpoint (Week 6). Paliperidone ER 1.5, 3.0, 6.0, or 12.0 mg or matching
      placebo will be administered daily in the morning before 10 a.m., and at approximately the
      same time each day. Study drug administration should occur in a consistent manner relative to
      the intake of food (i.e., either before or after breakfast, or without any breakfast)
      throughout the study. Study drug should be swallowed whole and with water. Study drug will be
      administered for 6 weeks.
    

Intervention name(s): Paliperidone ER; Placebo; Paliperidone ER; Paliperidone ER
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 3 mg or 6 mg tablet once daily for 6 weeks; Once daily for 6 weeks; 1.5 mg tablet once daily for 6 weeks; 6 mg or 12 mg tablet once daily for 6 weeks
Intervention MeSH terms: Paliperidone Palmitate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Schizophrenia; Antipsychotic