Paliperidone Extended Release Tablets for the Prevention of Relapse in Subjects With Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 201
- 主要终点
- Double Blind (DB) Phase: Median Time to Relapse
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, tolerability and safety of paliperidone extended release (ER) tablets (between 3 to 12 milligram (mg), once a day) in the prevention of relapse in schizophrenia participants.
详细描述
This is a double-blind (neither physician nor participant knows the name of the assigned drug), randomized (participants are assigned to treatment by a chance), placebo-controlled, and parallel-group study of paliperidone ER tablets. The study will consist of 6 phases: 14 days of screening phase, 8 weeks of open-label run-in phase (participants will be flexibly dosed with paliperidone ER once daily in a dose range of 3 mg to 12 mg), 6 weeks of stabilization phase (participants will continue to receive the fixed dose of paliperidone ER), double-blind (DB) phase of various length (participants will be randomly assigned in a 1:1 ratio to receive either paliperidone ER or placebo and this phase will be completed after 86 relapse events are observed or if the study is positive at the interim analysis), 6 months of open-label extension (participants who experience a relapse event or who remain relapse free for the entire duration of the double-blind phase and participants who are enrolled at the time the study is terminated, will be eligible for this phase. All participants will be treated with paliperidone ER and safety and tolerability information will be collected during this phase) phase and 6 months of follow-up phase (participants who withdraw during the DB phase for any reason other than relapse will be followed for 6 months or until they experience a relapse). Participants' safety will be monitored throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
- •Have experienced an acute episode, with a Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 inclusive, at Screening and Baseline
- •Women must be postmenopausal (for at least 1 year), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), practicing a highly effective method of birth control, if sexually active
- •Men must be using a highly effective method of birth control and must not donate sperm during the study and for 3 months after receiving the last dose of study drug
- •Be willing and capable to complete the questionnaires and able to take oral medications independently
排除标准
- •Has drug dependence diagnosis according to DSM-IV (excluding nicotine and caffeine dependence) within 6 months before screening
- •Participants with Crohn's disease and hepatic or renal diseases
- •Has had relevant history of any significant and/or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular dysfunction), renal, hepatic, endocrine, or immunologic diseases
- •Has had history of neuroleptic malignant syndrome (the disorder caused by antipsychotic drugs with symptoms of fever, muscle rigidity and delirium)
- •Has had known or suspected Stevens Johnson Syndrome (an immune disease with symptoms of fever, sore throat, ulcers and conjunctivitis) after exposure to phenytoin, carbamazepine, barbiturates, or lamotrigine
- •Had been treated with clozapine for treatment refractory or treatment resistant schizophrenia
- •Has significant risk of suicide or homicidal behavior, or significant risk of deliberate self harm or harm to others
- •Has taken isocarboxazid, phenelzine, selegiline and tranylcypromine within 4 weeks before screening
- •Has received electroconvulsive therapy within 60 days before screening
研究组 & 干预措施
Paliperidone: Run-in or Stabilization phase
Paliperidone extended-release (ER) oral tablet will be administered at a starting dose of 3 milligram (mg) once daily for 8 weeks. Dose will be increased from milligram per day (3 mg/day) after 5 days based on Investigator's discretion, up to maximum of 12 mg/day.
干预措施: Paliperidone (Drug)
Paliperidone: Double blind (DB) phase
Participants who transitioned from run-in or stabilization phase received 3 to 12 mg fixed dose of paliperidone ER oral tablet once daily during DB phase of the study. Participants who will experience a relapse event during the DB phase or who will remain relapse free for the entire duration of the DB phase and participants, who will be enrolled at the time the study termination will enter in open label extension phase, wherein paliperidone ER oral tablet will be administered once daily as 3 to 12 mg.
干预措施: Paliperidone (Drug)
Placebo: DB phase
Participants who transitioned from run-in or stabilization phase received matching placebo to paliperidone ER once daily during DB phase of the study. Participants who will experience a relapse event during the DB phase or who will remain relapse free for the entire duration of the DB phase and participants, who will be enrolled at the time the study termination will enter in open label extension phase, wherein paliperidone ER oral tablet will be administered once daily as 3 to 12 mg.
干预措施: Placebo (Drug)
结局指标
主要结局
Double Blind (DB) Phase: Median Time to Relapse
时间窗: DB Baseline (Day 1 of Week 15) up to interim analysis data cut-off (24 August 2012) (Approximately 1 year)
A relapse is defined as any one of the following: 1. involuntary or voluntary psychiatric hospitalization 2. deliberate self-injury or violent behavior; 3. Suicidal or homicidal ideation and clinically significant aggressive behavior; 4. 25 percent (%) increase in Positive and Negative Syndrome Scale (PANSS) total score for 2 consecutive assessments for participants whose score was greater than 40 at randomization, or a 10-point increase for participants who scored less than or equal to (≤) 40 at randomization; 5. increase for 2 consecutive assessments in PANSS items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, hostility or uncooperativeness) to greater than or equal to (≥) 5 for participants who scored ≤3 at randomization, or to ≥6 for participants with initial score of 4. Independent Data Monitoring Committee performed ongoing safety monitoring during double-blind treatment and conducted the interim analysis after 61 relapse events had taken place.
次要结局
- Run-In and Stabilization Phase: Change From Baseline in Personal and Social Performance (PSP) Scale Total Score at Week 14(Baseline and Week 14)
- Double Blind (DB) Phase: Change From DB Baseline in Personal and Social Performance (PSP) Scale Total Score at DB Endpoint(DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year]))
- Run-In and Stabilization Phase: Change From Baseline in Sleep Quality Based on Visual Analog Scale (VAS) at Week 14(Baseline and Week 14)
- Double Blind (DB) Phase: Median Time to Relapse (Final Analysis)(DB Baseline (Day 1 of Week 15) up to study completion (09 November 2012) (Approximately 1 year))
- Run-In and Stabilization Phase: Number of Participants Assessed With Categorical Scores Based on Clinical Global Impression-Severity Scale (CGI-S)(Baseline and Week 14)
- Double Blind (DB) Phase: Change From DB Baseline in Sleep Quality Based on Visual Analog Scale (VAS) at DB Endpoint(DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year]))
- Run-In and Stabilization Phase: Change From Baseline in Daytime Drowsiness Based on Visual Analog Scale (VAS) at Week 14(Baseline and Week 14)
- Run-In and Stabilization Phase: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 14(Baseline and Week 14)
- Double Blind (DB) Phase: Change From DB Baseline in Clinical Global Impression-Severity Scale (CGI-S) Total Score at DB Endpoint(DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year]))
- Open-label Extension (OLE) Phase: Change From OLE Baseline in Personal and Social Performance (PSP) Scale Total Score at OLE Endpoint(OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint))
- Double Blind (DB) Phase: Change From DB Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at DB Endpoint(DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year]))
- Double Blind (DB) Phase: Change From DB Baseline in Daytime Drowsiness Based on Visual Analog Scale (VAS) at DB Endpoint(DB Baseline (Day 1 of Week 15) up to DB endpoint (study completion [09 November 2012] [Approximately 1 year]))
- Open-label Extension (OLE) Phase: Change From OLE Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at OLE Endpoint(OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint))
- Open-label Extension (OLE) Phase: Change From OLE Baseline in Clinical Global Impression-Severity Scale (CGI-S) Total Score at OLE Endpoint(OLE Baseline (09 November 2012) up to OLE endpoint (that is, up to 24 Weeks [26 April 2013] from DB endpoint))