Clinical trial NCT00488319: Open-label Study of Flexible-dose Paliperidone ER (Extended Release) to Treat Adolescent Schizophrenia.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Schizophrenic Disorders
Psychotic Disorders
Dementia Praecox
Keywords: Schizophrenia
Adolescent
Paliperidone
Antipsychotic agents
Antipsychotic drugs
Psychosis.
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2007-06-20
Enrollment: 400
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Participants Who Experienced Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 2 years
Secondary outcomes:
measure: Change From Open-label Baseline to Open-label Endpoint in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Scores - Last Observation Carried Forward
timeFrame: Baseline, Week 104 or the last post-baseline assessment
measure: 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
timeFrame: Baseline, Week 104 or the last post-baseline assessment
measure: Change From Open-label Baseline to Open-label Endpoint in the Clinical Global Impression Severity (CGI-S) Scale - Last Observation Carried Forward
timeFrame: Baseline, Week 104 or the last post-baseline assessment
measure: Change From Open-label Baseline to Open-label Endpoint in the Children's Global Assessment Scale (CGAS) - Last Observation Carried Forward
timeFrame: Baseline, Week 104 or the last post-baseline assessment
measure: 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
timeFrame: Baseline, Week 24
measure: Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Attention/Working Memory Domain Test Variable Coding, Scaled - Last Observation Carried Forward
timeFrame: Baseline, Week 24
measure: Change From Open-label Baseline to Open-label Endpoint - Cognitive Domain: Attention/Working Memory Domain Test Variable Digit Span, Scaled - Last Observation Carried Forward
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: Change From Open Label Baseline to Open Label Endpoint - Cognitive Domain: Social Cognition Domain Test Variable - Theory of Mind-Total - Last Observation Carried Forward
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: 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
timeFrame: Baseline, Week 24
measure: Change From Open-label Baseline to Open-label Endpoint in the Sleep Visual Analog Scale (VAS): Quality of Sleep - Last Observation Carried Forward
timeFrame: Baseline, Week 104 or the last post-baseline assessment
measure: Change From Open-label Baseline to Open-label Endpoint in the Sleep Visual Analog Scale (VAS): Daytime Drowsiness - Last Observation Carried Forward
timeFrame: Baseline, Week 104 or the last post-baseline assessment
Other outcomes:
Locations:
city: Cerritos
country: United States
state: California
city: San Diego
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Middletown
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Jacksonville
country: United States
state: Florida
city: Coeur D Alene
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Lake Charles
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Las Vegas
country: United States
state: Nevada
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Antwerpen
country: Belgium
city: Sofia
country: Bulgaria
city: Tallinn
country: Estonia
city: Tartu N/A
country: Estonia
city: Viljandi N/A
country: Estonia
city: Hus
country: Finland
city: Kellokoski N/A
country: Finland
city: Chennai
country: India
city: Hyderabad
country: India
city: Mangalore
country: India
city: Varanasi
country: India
city: Cheonan City
country: Korea, Republic of
city: Gyeonggi-Do
country: Korea, Republic of
city: Kyunggi-Do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Gdansk
country: Poland
city: Lódź
country: Poland
city: Poznan N/A
country: Poland
city: Sosnowiec
country: Poland
city: Torun N/A
country: Poland
city: Warszawa
country: Poland
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 N/A
country: Russian Federation
city: Dnepropetrovsk
country: Ukraine
city: Glevakha
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Odessa
country: Ukraine
city: Simferopol
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Gopal S, Lane R, Nuamah I, Copenhaver M, Singh J, Hough D, Bach M, Savitz A. Evaluation of Potentially Prolactin-Related Adverse Events and Sexual Maturation in Adolescents with Schizophrenia Treated with Paliperidone Extended-Release (ER) for 2 Years: A Post Hoc Analysis of an Open-Label Multicenter Study. CNS Drugs. 2017 Sep;31(9):797-808. doi: 10.1007/s40263-017-0437-9.