An Efficacy and Safety Study of Paliperidone Extended-Release (ER) Tablets in Participants With Schizophrenia

Schizophrenia Clinical Trial

— PERTAIN  

Official title:

Tolerability, Safety and Treatment Response of Flexible Doses of Paliperidone ER in Acutely Exacerbated Subjects With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00566631
• Other study ID #: CR013162
• Secondary ID: R076477SCH3018
• Status: Completed
• Phase: Phase 3
• First received: November 29, 2007
• Last updated: June 27, 2013
• Start date: July 2007
• Est. completion date: May 2009

Study information

• Verified date: June 2013
• Source: Janssen-Cilag International NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ministry of Social Affairs, Public Health and the EnvironmentCroatia: Ministry of Health and Social Care
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the tolerability, safety and treatment response of flexible doses of paliperidone extended-release (ER; designed to slowly release a drug in the body over an extended period of time) tablets in participants with acute schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).

Description:

This is an open-label (all people know the identity of the intervention), single-arm (getting one dose of medicine), multi-center (conducted in more than 1 center) study to evaluate tolerability, safety and efficacy of flexible daily doses of paliperidone ER in participants with acute schizophrenia. All participants will be given paliperidone ER once daily at a dose of 3, 6, 9, or 12 milligram (mg) tablets orally depending on Investigator's discretion, based on participant's clinical response and tolerability towards paliperidone ER. The duration of the core phase of the treatment will be 6 weeks and the participants who will complete this phase, respond well and would like to continue, will be eligible to be enrolled in an extension phase, which is no longer than 12 months. Efficacy will primarily be evaluated by treatment response evaluated through total Positive and Negative Syndrome Scale (PANSS) score. Participants' safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 294
• Est. completion date: May 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia

• Must be experiencing an acute schizophrenic episode with a Positive and Negative Syndrome Scale (PANSS) total score of greater than or equal to 70 at Baseline

• Must be admitted to hospital for treatment of the acute schizophrenic episode and must agree for voluntary hospitalization for at least the first 7 days of the study

• Female participants must be postmenopausal (for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing and effective method of birth control (example, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study and female participants of child-bearing potential must have a negative urine pregnancy test at Screening

• Participants or their legally acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

• Pregnant or breast-feeding female participants

• First antipsychotic treatment ever

• Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment and on clozapine or a long-acting injectable antipsychotic during the last 3 months

• Known hypersensitivity to paliperidone extended-release (ER) or risperidone

• Relevant history of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases, history or current symptoms of tardive dyskinesia or neuroleptic malignant syndrome including recent or present clinically relevant laboratory abnormalities (as deemed by the Investigator) and participants with current or known history (over the past 6 months) of substance dependence according to DSM-IV Criteria

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Paliperidone
Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion will be given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag International NV

Countries where clinical trial is conducted

Croatia,  France,  Germany,  Israel,  Lithuania,  Poland,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation)	The AIMS is a 12-item scale to provide a numeric measure to the observed abnormal movements in different parts of the body. Information is collected after a brief neurological examination and is scored on a 5-point scale (0=none and 4=severe). Final evaluation is the last post-baseline visit with data.	Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)	Yes
Other	Change From Baseline in Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) Score at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation)	The SAS is a 10-item scale used to measure the symptoms of parkinsonism (slow movements) or parkinsonian side-effects related to the use of antipsychotic medications. The SAS rates 10 items (including gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, leg pendulousness, head dropping, Glabella tap, tremor and salivation), score ranging from 0 (normal) to 4 (extreme). The SAS global score is the average score (total sum of items score divided by the number of items) and ranges between 0 and 4, where the higher score indicates more severe condition of Extrapyramidal Symptoms. Final evaluation is the last post- baseline visit with data.	Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)	Yes
Other	Change From Baseline in Global Rating Sub-scale Score Based on Barnes Akathisia Rating Scale (BARS) at Day 7, 14, 42 and Final Evaluation (Day 42 or Early Discontinuation)	The BARS included an objective rating (from 0=normal to 3=constantly engaged), two subjective ratings of symptoms of akathisia, namely awareness of restlessness (ranging from 0=absence of inner restlessness to 3=awareness of intense compulsion to move) and reported distress related to restlessness (ranging from 0=no distress to 3=severe), and a global clinical rating of akathisia, ranging from 0 (absent) to 5 (severe). Global rating sub-scale score (that is, global clinical rating of akathisia) was assessed which was scored separately and is the most relevant measure of severity of akathisia. Higher scores indicates worsening akathisia. Final evaluation is the last post-baseline visit with data.	Baseline, Day 7, 14, 42 and Final Evaluation (Day 42 or early discontinuation)	Yes
Primary	Number of Participants With Treatment Response Based on Total PANSS Scale Score	Response was defined as decrease of at least 30 percent in total Positive and Negative Syndrome Scale (PANSS) score from Baseline to endpoint of core phase (which is, Day 42 or early discontinuation). The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, & poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of sum of all 30 PANSS items & ranges from 30 to 210. Higher scores indicate worsening.	Day 42 or early discontinuation	No
Secondary	Change From Baseline in Total Positive and Negative Symptom Scale (PANSS) Score at Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.	Baseline, Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)	No
Secondary	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Day 42 and Final Evaluation (Day 42 or Early Discontinuation)	The PANSS is a 30-item scale to assess neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms and disorganized thoughts subscale, consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement (H/E) subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28. Higher score indicates greater severity. Final evaluation is the last post-baseline visit with data.	Baseline, Day 42 and Final Evaluation (Day 42 or early discontinuation)	No
Secondary	Percentage of Participants With Treatment Response Greater Than (>) 20 Percent, 40 Percent and 50 Percent in Total Positive and Negative Syndrome Scale (PANSS) Score	The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data.	Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)	No
Secondary	Change From Baseline in Clinical Global Impression -Severity (CGI-S) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)	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. Final evaluation is the last post-baseline visit with data.	Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)	No
Secondary	Change From Baseline in Personal and Social Performance Scale (PSP) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)	The PSP assesses the degree of dysfunction within 4 domains of behavior: socially useful activities, personal & social relationships, self-care & disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 6, very severe) in each of 4 domains. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Final evaluation is the last post-baseline visit with data.	Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)	No
Secondary	Change From Baseline in Quality of Sleep Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)	The sleep evaluation scale is a self-administered scale that rates quality of sleep. Participants indicate on an 11-point scale that how well they have slept within the previous 7 days, score ranged from 0 (very badly) to 10 (very well). Final evaluation is the last post-baseline visit with data.	Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)	No
Secondary	Change From Baseline in Day Time Drowsiness Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation)	The day time drowsiness evaluation scale is a self-administered scale that rates day time drowsiness. Participants indicate on an 11-point scale that how often they have felt drowsy within the previous 7 days, score ranged from 0 (not at all) to 10 (all the time). Final evaluation is the last post-baseline visit with data.	Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation)	No
Secondary	Number of Participants Satisfied With the Study Treatment	Treatment satisfaction with paliperidone ER was assessed by the Investigator and participant on a 5-point scale: 1 (very good), 2 (good), 3 (reasonable), 4 (moderate) and 5 (poor), at the end of the core treatment phase (which is, Day 42 or early discontinuation) by conducting an interview.	Day 42 or early discontinuation	No

External Links

•   Tolerability, Safety and Treatment Response of Flexible Doses of Paliperidone ER in Acutely Exacerbated Subjects With Schizophrenia