Open-label Study of Flexible-dose Paliperidone ER (Extended Release) to Treat Adolescent Schizophrenia.

Schizophrenia Clinical Trial

Official title:

A 6-Month, Open-Label, Single-Arm Safety Study of Flexibly Dosed Paliperidone Extended Release (1.5 - 12 mg/Day) in the Treatment of Adolescents (12 to 17 Years of Age) With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00488319
• Other study ID #: CR012616
• Secondary ID: R076477PSZ3002
• Status: Completed
• Phase: Phase 3
• First received: June 18, 2007
• Last updated: November 12, 2013
• Start date: June 2007
• Est. completion date: July 2012

Study information

• Verified date: November 2013
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this open-label study is to evaluate the long-term (6-month) safety and tolerability of extended-release paliperidone, an atypical antipsychotic, given in flexible dosages to adolescents with schizophrenia.

Description:

This is a 6-month, open-label study (the patient, investigator, and sponsor know the study drug and dosage being taken by the patient) of the safety and tolerability of flexible-dose (1.5 to 12mg per day), extended-release (ER) paliperidone in adolescents with a diagnosis of schizophrenia. Patients who have completed study R076477PSZ3001 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. Patients may also enter this study directly without participating in R076477PSZ3001. This study consists of a 21-day screening and washout phase (to discontinue and "wash out" any medication not allowed in the study), an open-label treatment phase of up to 26 weeks during which all patients will take oral paliperidone ER every day, 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 either an inpatient or 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 physical examinations (including Tanner staging). The Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson Angus Rating Scale (SAS) will be used to assess extrapyramidal symptoms (EPS) and dyskinesias. Adverse events will be monitored including psychiatric adverse events of interest (i.e., suicide and related phenomena, homicidal ideation, depressed mood, and worsening of psychosis) that may be associated with paliperidone ER in this population. The primary aim of this study is to evaluate the long-term (6-month) safety and tolerability of paliperidone ER in adolescents with schizophrenia. As exploratory secondary aims, the study will assess the effect of 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-Severity (CGI-S) scale, the benefits in psychological, social, and school functioning as measured by the Children's Global Assessment Scale (CGAS), the changes in multiple domains of cognitive functioning measured by the modified Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) assessment battery, and the effect on sleep as measured by the sleep Visual Analog Scale (VAS). 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 or 1.5 mg/day. Patients will be dosed for up to 6 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• Meets the DSM-IV criteria for schizophrenia, otherwise physically healthy

• Weight >=63.9 pounds (29 kg)

• Must not be a danger to self or others and must have family support available to be maintained as outpatients

• Responsible adult must be available to accompany the patient to the investigational site at each visit.

Exclusion Criteria:

• Meets the DSM-IV criteria for dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, or primary substance-induced psychotic disorder

• mild, moderate, or severe mental retardation

• History of substance dependence (including alcohol, but excluding nicotine and caffeine) according to the DSM-IV criteria in the 3 months before screening

• pregnancy (for females)

• History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death in association with the use of drugs that prolong the QTc interval.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dementia Praecox.
• Disease
• Mental Disorders
• Psychotic Disorders
• Schizophrenia
• Schizophrenic Disorders

Intervention

Drug:
• Paliperidone ER
1.5 to 12 mg tablet once daily for 6 months

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Estonia,  Finland,  India,  Korea, Republic of,  Poland,  Romania,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Participants Who Experienced Adverse Events as a Measure of Safety and Tolerability	A serious adverse event as defined by the International Conference on Harmonisation (ICH) is any untoward medical occurrence that at any dose results in death, is life-threatening (the subject was at risk of death at the time of the even; it does not refer to an event that hypothetically might have caused death if it were more severe), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.	Up to 2 years	Yes
Secondary	Change From Open-label Baseline to Open-label Endpoint in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Scores - Last Observation Carried Forward	The PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).	Baseline, Week 104 or the last post-baseline assessment	No
Secondary	Change From Open-label Baseline to Open-label Endpoint in the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Based on Marder Factors - Last Observation Carried Forward	Neuropsychiatric symptoms of schizophrenia were assessed using the 30-item PANSS scale. PANSS scale provides a total score (sum of scores of all 30 items) and scores for 3 subscales, ie, positive (7 items), negative (7 items), and general psychopathology (16 items) subscales. Each item is scored on a scale of 1 (absent) to 7 (extreme). Positive Factor Score (range: 8 to 56): sum of select scores from positive, negative, and general psychopathology subscales. Negative Factor Score (range: 7 to 49): sum of select scores from negative and general psychopathology subscales. Disorganized Thoughts Factor Score (range: 7 to 49): sum of select scores from positive, negative, and general psychopathology subscales. Uncontrolled Hostility/Excitement Factor Score (range: 4 to 28): sum of select scores from positive and general psychopathology subscales. Anxiety/Depression Factor Score (range: 4 to 28): sum of select scores from general psychopathology subscale. Higher scores indicate worsening.	Baseline, Week 104 or the last post-baseline assessment	No
Secondary	Change From Open-label Baseline to Open-label Endpoint in the Clinical Global Impression Severity (CGI-S) Scale - Last Observation Carried Forward	The CGI-S rating scale is a 7-point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.	Baseline, Week 104 or the last post-baseline assessment	No
Secondary	Change From Open-label Baseline to Open-label Endpoint in the Children's Global Assessment Scale (CGAS) - Last Observation Carried Forward	The CGAS is a 100 point rating scale which measures the psychological, social, and school functioning for children 6 to 17 years of age. The score ranges from 1 to 100, divided into 10 equal intervals to rate the impairment level of general functioning (poor to superior functioning). Higher scores denote better functioning.	Baseline, Week 104 or the last post-baseline assessment	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Motor Speed Domain Test Variable, Finger Tapping Dominant- and Non-Dominant Hand, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Attention/Working Memory Domain Test Variable Coding, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Attention/Working Memory Domain Test Variable Digit Span, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label - Cognitive Domain: Verbal Learning and Memory Domain Test Variable Wide Range Assessment of Memory and Learning Story - Total, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Verbal Learning and Memory Domain Test Variable California Verbal Learning Test-Total Trials, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Visual Learning and Memory Domain Test Variable, Rey Complex Figure Test - Total, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open Label Baseline to Open Label Endpoint - Cognitive Domain: Social Cognition Domain Test Variable - Theory of Mind-Total - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open Label Baseline to Open Label Endpoint - Cognitive Domain: Speed of Processing Domain Test Variable Trials Part A Time: Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Speed of Processing Domain Test Variable Child Color Trials Test 1 Time: Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Speed of Processing Domain Test Variable Phonetic Verbal Fluency: Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Speed of Processing Domain Test Variable Semantic Verbal Fluency, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Executive Functioning (Reasoning and Problem Solving) Domain Test Variable, Trials Part B Time, Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Executive Functioning (Reasoning and Problem Solving) Domain Test Variable - Wisconsin Card Sort Test-Total Errors: Scaled - Last Observation Carried Forward	A comprehensive neuropsychological examination that measures different domains of cognitive functioning is provided. They are either assessed as T-scores [mean=50, SD=10 range 1-100]; z-scores [mean=0, SD=1, and can be positive or negative] or scaled scores [mean=10, SD=3, and can be positive or negative]. The theory-of-mind total score is a raw score that ranges from 1 to 100. Higher scores for all scales denote better performance.	Baseline, Week 24	No
Secondary	Change From Open-label Baseline to Open-label Endpoint in the Sleep Visual Analog Scale (VAS): Quality of Sleep - Last Observation Carried Forward	Sleep VAS is a self administered scale that rates the quality of sleep and daytime drowsiness. Participants make a mark on a line to represent how well they have slept in the previous 7 days ("very badly" to "very well") and how often they have felt drowsy within the previous 7 days ("not at all" to "all the time"). The score for each item ranges from 0 to 100 mm. For quality of sleep, a score of 0 indicates "Very badly" and a score of 100 indicates "Very well." For daytime drowsiness, a score of 0 indicates "Not at all" and a score of 100 indicates "All the time." Improvement of the condition is indicated by the positive change for the quality of sleep and the negative change for the daytime drowsiness.	Baseline, Week 104 or the last post-baseline assessment	No
Secondary	Change From Open-label Baseline to Open-label Endpoint in the Sleep Visual Analog Scale (VAS): Daytime Drowsiness - Last Observation Carried Forward	Sleep VAS is a self administered scale that rates the quality of sleep and daytime drowsiness. Participants make a mark on a line to represent how well they have slept in the previous 7 days ("very badly" to "very well") and how often they have felt drowsy within the previous 7 days ("not at all" to "all the time"). The score for each item ranges from 0 to 100 mm. For quality of sleep, a score of 0 indicates "Very badly" and a score of 100 indicates "Very well." For daytime drowsiness, a score of 0 indicates "Not at all" and a score of 100 indicates "All the time." Improvement of the condition is indicated by the positive change for the quality of sleep and the negative change for the daytime drowsiness.	Baseline, Week 104 or the last post-baseline assessment	No