Randomized, Double-blind, Placebo Controlled, Multi-center and Tolerability of RBP-7000 in Schizophrenia Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of RBP-7000 compared with placebo in the treatment of patients with schizophrenia. This will be a double-blind, placebo-controlled, Phase III study with 90 mg and 120 mg doses of RBP-7000 compared with placebo over an 8-week treatment period.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of RBP-7000 as a Treatment in Subjects With Acute Schizophrenia Over 8 Weeks (2 Subcutaneous Doses)

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: RBP-7000
* Drug: Placebo
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 18 to 55 years, inclusive Diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual, Edition 4, text revision (DSM-IV-TR) criteria Subjects who are deemed valid by the State, Assessability, Face, Ecological, and Rule (SAFER) interview Subjects who are otherwise healthy on the basis of their physical examination Exclusion Criteria: Subjects who have an improvement in their total Positive and Negative Syndrome Scale (PANSS) score of 20% or greater between the initial screening visit and the first day of treatment. Subjects taking daily oral risperidone at a dose ≥ 6 mg/day Subjects who have received a depot antipsychotic within 120 days of screen Subjects with treatment resistant schizophrenia, as judged by the investigator, who have been treated with antipsychotics for adequate durations and with adequate dosages.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RBP-7000 90 mg<br>Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 90 mg subcutaneous injection on Days 1 and 29 for a total of two injections. | Drug: RBP-7000<br>* RBP-7000 90 mg and 120 mg were a mixture of the ATRIGEL Delivery System and 90 mg and 120 mg risperidone, respectively. The ATRIGEL Delivery System allows for sustained-release of risperidone in a controlled manner. Subcutaneous RBP-7000 injections on Days 1 and 29 in the lower quadrant of the abdomen rotating right and left on day 1 and 29.<br>* Other names: risperidone in Atrigel;Drug: Risperidone<br>* Oral risperidone 0.25 mg tablets daily for the first two days of the screening period. The two 0.25 mg tablets confirmed whether study participants had any negative reaction to risperidone prior to receiving a long-acting injection of risperidone (RBP-7000).<br>* Other names: Risperdal;|
| Experimental: RBP-7000 120 mg<br>Risperidone tablets given during the screening period to check for sensitivity. RBP-7000 administered as a 120 mg subcutaneous injection on Days 1 and 29 for a total of two injections. | Drug: RBP-7000<br>* RBP-7000 90 mg and 120 mg were a mixture of the ATRIGEL Delivery System and 90 mg and 120 mg risperidone, respectively. The ATRIGEL Delivery System allows for sustained-release of risperidone in a controlled manner. Subcutaneous RBP-7000 injections on Days 1 and 29 in the lower quadrant of the abdomen rotating right and left on day 1 and 29.<br>* Other names: risperidone in Atrigel;Drug: Risperidone<br>* Oral risperidone 0.25 mg tablets daily for the first two days of the screening period. The two 0.25 mg tablets confirmed whether study participants had any negative reaction to risperidone prior to receiving a long-acting injection of risperidone (RBP-7000).<br>* Other names: Risperdal;|
| Placebo Comparator: Placebo<br>Risperidone tablets given during the screening period to check for sensitivity. Placebo administered by subcutaneous injection on Days 1 and 29 for a total of two injections. | Drug: Placebo<br>* Subcutaneous injection of placebo using the ATRIGEL Delivery System on Days 1 and 29 in the lower quadrant of the abdomen rotating right and left on day 1 and 29.<br>Drug: Risperidone<br>* Oral risperidone 0.25 mg tablets daily for the first two days of the screening period. The two 0.25 mg tablets confirmed whether study participants had any negative reaction to risperidone prior to receiving a long-acting injection of risperidone (RBP-7000).<br>* Other names: Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mixed Model for Repeated Measures (MMRM) Analysis of Change From Baseline to End of Treatment in the Positive and Negative Syndrome Scale (PANSS) Total Score | The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor judgement, 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 is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicate improvements in symptoms. Estimates (least square means and standard errors), 2-sided confidence intervals, and -1-sided P values are based on a repeated-measures linear regression model of the change from baseline score, with fixed effects for visit as a categorical variable, baseline score, treatment and treatment by visit interaction, assuming an unstructured covariance matrix. | Day 1 prior to treatment (Baseline), Days 15, 29, 43 and 57 or early discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mixed Model for Repeated Measures (MMRM) Analysis of Change From Baseline to End of Treatment in Clinical Global Impression - Severity Scale (CGI-S) | 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. Negative change from baseline scores indicate improvement in the severity of illness. Estimates (least square means and standard errors), 2-sided confidence intervals, and -1-sided P values are based on a repeated-measures linear regression model of the change from baseline score, with fixed effects for visit as a categorical variable, baseline score, treatment and treatment by visit interaction, assuming an unstructured covariance matrix. | Day 1 prior to treatment (Baseline), Days 15, 29, 43 and 57 or early discontinuation | 
| Summary of Participants With Treatment-Emergent Adverse Events (TEAE) | An adverse event (AE) is defined as any study-related event that represents a change (positive or negative) in frequency or severity from a baseline (prestudy) event (if any), regardless of the presence of causal relationship or medical significance. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the first study dose date. AEs are determined by the Investigator to be related or not related to the study drug. A serious AE (SAE) is defined by federal regulation as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Although a subject may have had 2 or more adverse experiences the subject is counted only once in a category. The same subject may appear in different categories. | Day 1 to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenic, Schizophrenias, Risperidone, Schizophrenia