Tolerability, Safety and Efficacy of Flexibly Dosed Paliperidone ER in Patients With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy, safety and tolerability of flexible, once-daily doses of paliperidone extended-release (ER) in patients with schizophrenia from Argentina and Colombia that previously failed treatment with other antipsychotic agents.

Detailed Description
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This is a single arm (one group of patients), open-label (all people know the identity of the intervention) multicenter 6-month study. Throughout the study flexible dosing of paliperidone ER in a range of 3 to 12 mg/day may be used. Flexible dosing will allow investigators to adjust the dosage of each patient based on the individual needs. Patients will receive 3, 6, 9 or 12 mg of paliperidone ER once daily for 6 months. The tablets will be taken orally. Adjustment of the dosage will be done at the investigator's discretion, based on the individual patient's clinical response and tolerability to the study drug.

Official Title
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An Open-label Prospective Trial to Explore the Tolerability, Safety and Efficacy of Flexibly Dosed Paliperidone ER in Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Paliperidone ER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient meets the criteria for schizophrenia Patient is previously non-acute and has been given an adequate dose of an appropriate oral antipsychotic for an adequate period of time prior to enrollment, but previous treatment is considered unsuccessful due to one or more of the following reasons: lack of efficacy, lack of tolerability or safety, lack of compliance and/or other reasons to switch to another antipsychotic medication Patient is healthy on the basis of a physical examination and vital signs at screening Women must be postmenopausal for at least 1 year, surgically sterile, abstinent, or, if sexually active, agree to practice an effective method of birth control before entry and throughout the study Exclusion Criteria: Patients on clozapine, any conventional depot neuroleptic or risperidone long-acting injections during the last 3 months Patients with serious unstable medical condition, including known clinically relevant laboratory abnormalities Patients with history or current symptoms of tardive dyskinesia and neuroleptic malignant syndrome Patients judged to be at high risk for adverse events, violence, or self-harm Patients with known hypersensitivity to paliperidone ER or to risperidone Patients with a current use or known history (over the past 6 months) of substance dependence

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paliperidone ER<br> | Drug: Paliperidone ER<br>* The recommended Paliperidone extended-release (ER) dose will be 6 mg/day. Some patients may benefit from higher or lower doses, in the range of 3 to 12 mg/day. Paliperidone ER will be administered orally once daily. Adjustment of the dosage will be done at the investigator's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score | The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia. 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. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score | The PANSS Positive Subscale assesses seven positive-symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology). | Baseline, Week 26 | 
| Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score | The PANSS Negative Subscale assesses seven negative-symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology). | Baseline, Week 26 | 
| Change From Baseline in Total Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score | The PANSS General Psychopathology Subscale Score assesses 16 general psychopathology symptoms. The symptoms are rated on a 7-point scale, with a range of 16 (absent) to 112 (extreme psychopathology). | Baseline, Week 26 | 
| Clinical Global Impression-Severity (CGIS) | 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 patient. 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 patients. Higher scores indicate worsening. | Baseline, Week 26 | 
| Personal and Social Performance (PSP) Scale | This PSP assesses the degree of a patient's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (i, absent to vi, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Patients with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; =< 30, functioning so poorly as to require intensive supervision. | Baseline, Week 26 | 
| Health Status as Measured by Self-rated Health Status Survey SF-36 | The SF-36 is designed to examine a person's perceived health status. The SF-36 includes one multi-item scale measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health. Answers to each question are scored and summed to produce raw scale scores for each health concept which are then transformed to a 0 - 100 scale, a high score defining a more favorable health state. An aggregate summary measure is calculated by averaging the scores from the eight health concepts. | Baseline, Week 26 | 
| Sleep Evaluation Scale | This self-administered scale rates the quality of sleep. Patients will indicate on an 11-point scale how well they have slept in the previous 7 days, from 0 (very badly) to 10 (very well). | Baseline, Week 26 | 
| Daytime Drowsiness Evaluation Scale | This self-administered scale rates the daytime drowsiness. Patients will indicate on an 11-point scale how often they have felt drowsy within the previous 7 days, from 0 (not at all) to 10 (all the time). | Baseline, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Paliperidone extended-release (ER), Antipsychotic agents