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

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)

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: RBP-7000; Drug: Risperidone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, Inc.
    • Springdale, Arkansas, United States, 72764
      • Woodland International Research Group, Inc.
  • California
    • Cerritos, California, United States, 90703
      • Comprehensive Clinical Development - Cerritos, CA
    • Escondido, California, United States, 92025
      • Synergy Clinical Research of Escondido
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • Long Beach, California, United States, 90813
      • Apostle Clinical Trials, Inc.
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Networks, Inc.
    • Oakland, California, United States, 94612
      • Pacific Research Partners
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Pico Rivera, California, United States, 90660
      • CNRI- LOs Angeles, LLC
    • San Diego, California, United States, 92012
      • CNRI - San Diego, LLC
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Innovative Clinical Research
    • North Miami, Florida, United States, 33021
      • Behavioral Clinical Research, Inc.
    • Orlando, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute
    • Hoffman Estates, Illinois, United States, 60169
      • Alexian Brothers Behavioral Health Hospital
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Via Christi Research
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials, LLC
    • Shreveport, Louisiana, United States, 71104-2136
      • J. Gary Booker, MD, APMC
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
    • Saint Louis, Missouri, United States, 63118
      • St. Louis Clinical Trials
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research Institute
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • CRI Lifetree
  • New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • New Hope Clinical Research
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma Clinical Research Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Lifetree
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research, Inc.
    • Austin, Texas, United States, 78734
      • FutureSearch Clinical Trials, L.P.
    • Dallas, Texas, United States, 75231
      • FutureSearch Clinical Trials, L.P.
    • Dallas, Texas, United States, 75243
      • Pillar Clinic Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RBP-7000 90 mg; 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; 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.; Other Names: risperidone in Atrigel; Drug: Risperidone; 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).; Other Names: Risperdal
Experimental: RBP-7000 120 mg; 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; 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.; Other Names: risperidone in Atrigel; Drug: Risperidone; 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).; Other Names: Risperdal
Placebo Comparator: Placebo; 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: Risperidone; 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).; Other Names: Risperdal; Drug: Placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Indivior Inc.
• Investigators: Study Director: Global Clinical Developoment Manager, Indivior Inc.

Publications and helpful links

General Publications

• Andrade C. Prazosin for Alcohol Use Disorder: Reply to Sinha. J Clin Psychiatry. 2021 Sep 21;82(6):21lr14076a. doi: 10.4088/JCP.21lr14076a. No abstract available.
• Sinha R. Prazosin for Alcohol Use Disorder: A Clarification. J Clin Psychiatry. 2021 Sep 21;82(6):21lr14076. doi: 10.4088/JCP.21lr14076. No abstract available.
• Le Moigne A, Csernansky J, Leadbetter RA, Andorn AC, Graham JA, Heath AT, Walling DP, Newcomer JW, Marder SR. PANSS Individual Item and Marder Dimension Analyses From a Pivotal Trial of RBP-7000 (Monthly Extended-Release Risperidone) in Schizophrenia Patients. J Clin Psychiatry. 2021 Sep 21;82(5):21m13906. doi: 10.4088/JCP.21m13906.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: April 7, 2014
• First Posted (Estimate): April 10, 2014

Study Record Updates

• Last Update Posted (Actual): October 26, 2018
• Last Update Submitted That Met QC Criteria: October 22, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Schizophrenia; Risperidone; Schizophrenic; Schizophrenias
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: RB-US-09-0010