A Double-blind, Placebo-controlled Study of the Safety and Efficacy of Paliperidone Extended Release (ER) in the Treatment of Schizophrenia in Adolescent Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00518323
First received: August 16, 2007
Last updated: March 25, 2014
Last verified: November 2010
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Paliperidone ER
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Double-Blind, Weight-Based, Fixed-Dose, Parallel-Group, Placebo-Controlled Study of the Efficacy and Safety of Extended Release Paliperidone for the Treatment of Schizophrenia in Adolescent Subjects, 12 to 17 Years of Age

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Change in the PANSS Total Score From Baseline to the Last Postrandomization Assessment in the Double-blind Period of the Study. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The Positive and Negative Syndrome Scale (PANSS) measures the severity of psychotic symptoms of schizophrenia. Scores range from 30 to 210, where 30=best and 210=worst. The change in PANSS total score for all eligible subjects was measured from the beginning of the study to the end.


Secondary Outcome Measures:
  • Change From Baseline to End Point in Clinical Global Impression-Severity (CGI-S) Scale [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The CGI-S rating scale was used to assess the severity of a subject's overall clinical condition. Scores range from 1 to 7, where 1=best and 7=worst.

  • Change From Baseline to End Point in Children's Global Assessment (CGAS) Score [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The CGAS score assesses psychological, social, and school functioning for children 6 to 17 years of age. Scores range from 1 to 100, where 100=best and 1=worst.

  • Change From Baseline to End Point in Sleep Visual Analog Scale (VAS) for Quality of Sleep. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The sleep VAS for sleep quality is a scale for measuring the quality of sleep experienced by a patient. Scores range from 0 to 100, where 100=best and 0=worst.

  • Change From Baseline to End Point in Sleep VAS for Daytime Drowsiness [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The sleep VAS for daytime drowsiness is a scale for measuring the drowsiness experienced by a patient. Scores range from 0 to 100, where 100=best and 0=worst.


Enrollment: 201
Study Start Date: August 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Paliperidone ER 1.5 mg tablet once daily for 6 weeks
Drug: Paliperidone ER
1.5 mg tablet once daily for 6 weeks
Experimental: 002
Paliperidone ER 3 mg or 6 mg tablet once daily for 6 weeks
Drug: Paliperidone ER
3 mg or 6 mg tablet once daily for 6 weeks
Experimental: 003
Paliperidone ER 6 mg or 12 mg tablet once daily for 6 weeks
Drug: Paliperidone ER
6 mg or 12 mg tablet once daily for 6 weeks
Placebo Comparator: 004
Placebo Once daily for 6 weeks
Drug: Placebo
Once daily for 6 weeks

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.

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must meet the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria for schizophrenia (295.10, 295.20, 295.30, 295.60, 295.90) for 1 year (the diagnosis will be established using the K-SADS-PL, including all supplements)
  • Must not be a danger to themselves or others, and must have family support available to be maintained as an outpatient
  • Should have had at least 1 adequate treatment with an antipsychotic before participation in this study
  • Must have a PANSS score between 60 and 120, inclusive, at screening and baseline
  • Weight >=29 kg

Exclusion Criteria:

  • Meet the DSM-IV criteria at screening for dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, or primary substance induced psychotic disorder. Other comorbid disorders e.g., attention-deficit hyperactivity disorder (ADHD) are allowed as long as the diagnosis of schizophrenia is the primary diagnosis and the comorbid disorders in the investigator's judgment do not require medication
  • Mild, moderate, or severe mental retardation (i.e., documented intelligence quotient [IQ] <70) established by previous IQ testing or history
  • Women who are pregnant (as confirmed by urine pregnancy test performed at screening or baseline), planning to become pregnant or are nursing
  • Have a known or suspected history of seizure disorder, or neuroleptic malignant syndrome, encephalopathic syndrome, tardive dyskinesia, or insulin dependent diabetes mellitus
  • Presence of any significant or unstable cardiovascular, respiratory, renal, hepatic, hematologic, endocrine, immunologic, or other systemic disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00518323

  Show 35 Study Locations
Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00518323     History of Changes
Other Study ID Numbers: CR002368, R076477PSZ3001
Study First Received: August 16, 2007
Results First Received: March 23, 2010
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Schizophrenia
Antipsychotic

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
9-hydroxy-risperidone
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 28, 2014