An Open-Label, Long-Term Safety and Tolerability Study of RBP-7000 in the Treatment of Subjects With Schizophrenia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 500
- 试验地点
- 47
- 主要终点
- Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •"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
排除标准
- •"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
研究组 & 干预措施
RBP-7000 - 120-mg dose
RBP-7000 120-mg subcutaneous (SC) injections every 28 days for 13 doses as open-label therapy. Patients enter the study as 'roll-over' patients from study RB-US-09-0010, or de novo patients. Pre-study procedures vary for de novo patients depending on previous therapy.
干预措施: RBP-7000 (Drug)
结局指标
主要结局
Participants With Injection Site-Related Treatment-Emergent Adverse Events (TEAEs)
时间窗: Day 1 up to week 52
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. Adverse events were coded using MedDRA version 17.0. Preferred terms linked to injection site AEs are reported. Although a participant may have had 2 or more AEs, the subject is counted only once in each preferred term category. The same subject may appear in different preferred term categories.
Participants With Markedly Abnormal Weight Gain Anytime During the Study as Compared to Baseline
时间窗: Baseline (Day 0), Treatment (Day 1 up to Week 52)
Participants who were found to have gain \>=7% and \>=10% of their baseline weight at any point during the study (including unscheduled assessments) once treatment began.
Participants With Treatment-Emergent Adverse Events (TEAE)
时间窗: Day 1 up to week 52
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.
次要结局
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Subscale Scores to End of Study(Baseline (Day 0), End of Study (approximately Week 52))
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score to Days 29, 169 and End of Study(Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52))
- Change From Baseline in Clinical Global Impression - Severity Scores (CGI-S) to Days 29, 169 and End of Study(Baseline (Day 0), Baseline (Day 0), Day 29, Day 169 and End of Study (approximately Week 52))