Clinical trial NCT00518323: A Double-blind, Placebo-controlled Study of the Safety and Efficacy of Paliperidone Extended Release (ER) in the Treatment of Schizophrenia in Adolescent Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
Antipsychotic
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2007-08-20
Enrollment: 201
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility 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

Primary outcomes:
measure: Change in the PANSS Total Score From Baseline to the Last Postrandomization Assessment in the Double-blind Period of the Study.
timeFrame: 6 weeks
Secondary outcomes:
measure: Change From Baseline to End Point in Clinical Global Impression-Severity (CGI-S) Scale
timeFrame: 6 weeks
measure: Change From Baseline to End Point in Children's Global Assessment (CGAS) Score
timeFrame: 6 weeks
measure: Change From Baseline to End Point in Sleep Visual Analog Scale (VAS) for Quality of Sleep.
timeFrame: 6 weeks
measure: Change From Baseline to End Point in Sleep VAS for Daytime Drowsiness
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Cerritos
country: United States
state: California
city: Fountain Valley
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Lake Charles
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Cleveland
country: United States
state: Ohio
city: Portsmouth
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Bangalore
country: India
city: Chennai
country: India
city: Hyderabad Andra Pradesh
country: India
city: Hyderabad
country: India
city: Mangalore
country: India
city: New Delhi
country: India
city: Varanasi
country: India
city: Bucharest
country: Romania
city: Ekaterinburg Na
country: Russian Federation
city: Kazan
country: Russian Federation
city: Moscow N/A
country: Russian Federation
city: Moscow Russia
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Saratov N/A
country: Russian Federation
city: Smolensk Region N/A
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Stavropol Na
country: Russian Federation
city: Tomsk Na
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Glevakha
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Odessa
country: Ukraine
city: Simferopol
country: Ukraine
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Sliwa JK, Fu DJ, Bossie CA, Turkoz I, Alphs L. Body mass index and metabolic parameters in patients with schizophrenia during long-term treatment with paliperidone palmitate. BMC Psychiatry. 2014 Feb 22;14:52. doi: 10.1186/1471-244X-14-52.
citation: Opler M, Malaspina D, Gopal S, Nuamah I, Savitz AJ, Singh J, Hough D. Effect of parental age on treatment response in adolescents with schizophrenia. Schizophr Res. 2013 Dec;151(1-3):185-90. doi: 10.1016/j.schres.2013.10.001. Epub 2013 Oct 18.