Clinical trial NCT02203838: Long Term Study of RBP 7000 in the Treatment of Subjects With Schizophrenia
Official title: An Open-Label, Long-Term Safety and Tolerability Study of RBP-7000 in the Treatment of Subjects With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
Schizophrenic
Schizophrenias
Risperidone
Long-acting Risperidone
Atrigel
Subcutaneous
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2014-07-30
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, open label study administering RBP-7000 in the treatment of patients with schizophrenia. Study will assess the long-term safety and tolerability of RBP-7000 subcutaneous (SC) injections in subjects with schizophrenia and to continue collecting clinical outcome data with RBP-7000 SC injections in subjects with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Illness (CGI-S) scale.

Detailed description: Patients to be screened must be diagnosed with schizophrenia with a designated score based on the PANSS, as confirmed by a State, Assessability, Face, Ecological and Rule (SAFER) interview. "De novo" patients are patients who are already receiving 3- or 4-mg oral risperidone/day and will not have to complete the "run-in" or "conversion" phases (see below) and will be assigned to receive RBP-7000 after eligibility has been confirmed. Patients who completed the double-blind, placebo-controlled, efficacy study of RBP-7000 (RB-US-09-0010, NCT02109562), conducted in patients with acute schizophrenia (referred to as "roll-over" patients) will be screened.

All patients will be assigned the 120 mg dose of RBP-7000, which is subject to a one-time down-titration to 90-mg RBP-7000 for tolerability, at the investigator's discretion. Patients receiving the 90-mg dose of RBP-7000 who exhibit a worsening in psychiatric symptoms, confirmed by a total PANSS score \>70 or a 20% increase in the PANSS score from the previous assessment at the 120-mg dose level (before the dose was decreased to 90 mg), can receive a one-time, up-titration back to 120-mg RBP-7000 at the discretion of the investigator.

"De novo" patients entering into the study are those patients who did not participate in study RB-US-09-0010 (NCT02109562) and are allocated into three groups with different pre-study procedures to prepare for the treatment period:

* "Run-in" patients are patients who are not already receiving oral risperidone (as no other antipsychotic medications are allowed during study participation) and will begin a 14-day run-in period by titrating up to a dose of 3 or 4 mg oral risperidone/day before the first injection of RBP-7000.
* "Conversion" patients are patients who are receiving oral risperidone doses other than 3 or 4mg/day and will begin a 7-day conversion period to achieve an oral risperidone dose level of 3 or 4-mg before the first injection of RBP-7000, only if clinically indicated.
* De novo patients taking an oral risperidone dose of 3 or 4 mg/day prestudy will (once screened/enrolled) receive the first injection of RBP-7000.

"Roll-over" patients entering into the study are patients who completed 56 days of double-blind treatment in Study RB-US-09-0010. These patients will be eligible to enter the current study provided that continuation of treatment is clinically warranted, as judged by the investigator, and that there have been no significant protocol deviations or clinically relevant adverse events (AEs) that would preclude inclusion in this study. Roll-over patients will not undergo the complete screening process and will not require either a run-in or conversion period with oral risperidone. On Day 1 of the open-label study (which is Day 57 of Study RB-US-09-0010), patients will receive their first injection (120 mg) of open label RBP-7000.

Eligibility criteria: Inclusion Criteria:

"De Novo" Patients

* Diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual, Edition 4, text revision (DSM-IV-TR) criteria
* Total PANSS score \<=70 at the time of screening (Visit 1)
* Otherwise healthy on the basis of physical examinatIon
* Provided written informed consent

"Roll-over Patients

* Provided written consent to participate in this study
* Be considered eligible to enroll based on End of Study (EOS) (Day 57 of Study RB-US-09-0010) assessments and the medical judgment of the investigator

Exclusion Criteria:

"De Novo" Patients

* Patients taking daily oral risperidone at a dose plus/minus 6 mg/day
* Patients taking any risperidone or 9-hydroxyrisperidone long-acting injectable formulation within 120 days of study screening (Visit 1)
* Patients who have received a long-acting injectable antipsychotic within 120 days of screening (Visit 1)
* Patients with evidence or history (in the past six months prior to screening) of a significant hepatic disorder that may either compromise patient safety or interfere with the safety and/or outcome evaluation of the study drug, including:

  * Acute or chronic hepatitis, including but not limited to hepatitis B or C
  * Total bilirubin greater than 1.5 times the upper limit of normal (ULN), or
  * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times ULN
* Patients with a history of drug-induced leukopenia
* Patients with other medical conditions including, but not limited to, history of heart attack (myocardial infarction) or brain injury (traumatic injury with loss of consciousness and/or cerebrovascular accident), and clinically significant low blood pressure or arrhythmias as interpreted by the primary investigator (PI) or medically qualified sub-investigator
* Patients with epilepsy or other seizure disorders, Parkinson's disease or dementia

"Roll-over" Patients

* Patients requiring an inpatient treatment setting at the end of Study RB-US-09-0010
* Patients with an unstable medical condition developed during Study RB-US-09-0010
* Women of childbearing potential who have a positive pregnancy test at screening (Visit 1), who are pregnant or breastfeeding, seeking pregnancy, or failing to use adequate contraceptive methods during the study

Primary outcomes:
measure: Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: Day 1 up to week 52
measure: Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to week 52
measure: Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline
timeFrame: Baseline (Day 0), Treatment (Day 1 up to Week 52)
Secondary outcomes:
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study
timeFrame: Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study
timeFrame: Baseline (Day 0), End of Study (approximately Week 52)
measure: Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study
timeFrame: Baseline (Day 0), Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Woodland International Research Group, Inc.
state: Arkansas
city: Springdale
country: United States
facility: Woodland Research Northwest, LLC
state: Arkansas
city: Cerritos
country: United States
facility: Comprehensive Clinical Development
state: California
city: Escondido
country: United States
facility: Synergy EPIC
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
city: Long Beach
country: United States
facility: Apostle Clinical Trials
state: California
city: Oakland
country: United States
facility: Pacific Research Partners
state: California
city: Oceanside
country: United States
facility: Excell Research
state: California
city: Pico Rivera
country: United States
facility: CNRI-Los Angeles
state: California
city: San Diego
country: United States
facility: CNRI-San Diego
state: California
city: Norwalk
country: United States
facility: Research Center for Clinical Studies
state: Connecticut
city: Washington
country: United States
facility: Comprehensive Clinical Development-Washington DC
state: District of Columbia
city: Bradenton
country: United States
facility: Florida Clinical Research Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Innovative Clinical Research
state: Florida
city: Hollywood
country: United States
facility: Behavioral Clinical Reserach
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center
state: Florida
city: Miami
country: United States
facility: Premier Clinical Resarch Institute
state: Florida
city: Atlanta
country: United States
facility: Radiant Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Chicago
country: United States
facility: Uptown Research Institute
state: Illinois
city: Hoffman Estates
country: United States
facility: Behavioral Health Hospital
state: Illinois
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Wichita
country: United States
facility: Via Christi Research
state: Kansas
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: Saint Charles
country: United States
facility: Centerpointe Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research Institute
state: Nevada
city: Marlton
country: United States
facility: CRI Lifetree - Marlton Unit
state: New Jersey
city: Brooklyn
country: United States
facility: Behavioral Medical Research of Brooklyn
state: New York
city: Cedarhurst
country: United States
facility: Neurobehavioral Research
state: New York
city: Jamaica
country: United States
facility: Comprehensive Clinical Development-Queens
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research
state: North Carolina
city: Hickory
country: United States
facility: Clinical Trials of America
state: North Carolina
city: Shaker Heights
country: United States
facility: Insight Clinical Trials LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Norristown
country: United States
facility: Keystone Clinical Studies
state: Pennsylvania
city: Philadelphia
country: United States
facility: CRI Lifetree - Philadelphia Unit
state: Pennsylvania
city: Reading
country: United States
facility: Berks Center for ClinicalResearch
state: Pennsylvania
city: Memphis
country: United States
facility: Research Strategies of Memphis
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Clinical Trials
state: Texas
city: Austin
country: United States
facility: Community Clinical Research, Inc.
state: Texas
city: Dallas
country: United States
facility: FutureSearch Clinical Trials, L.P.
state: Texas
city: Dallas
country: United States
facility: Pillar Clinical Research
state: Texas
city: Houston
country: United States
facility: Bayou City Research
state: Texas
city: Richmond
country: United States
facility: Alliance Research Group
state: Virginia
Study officials:
affiliation: Indivior Inc.
name: Indivior Inc.
role: STUDY_DIRECTOR
References: