A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine as an Active Control in Subjects With an Acute Exacerbation of Schizophrenia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 360
- 主要终点
- Change From Baseline in PANSS Total Score at Day 42
研究概览
简要总结
The purpose of this trial is to assess the effect of asenapine 2.5 and 5 mg sublingually twice daily (BID) compared with placebo in the treatment of schizophrenia (overall symptoms) as measured by the Positive and Negative Syndrome Scale (PANSS). Olanzapine administered 15 mg orally once daily (QD) was used as an active control. The primary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the change from Baseline in the PANSS total score at Day 42. The first key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the change from Baseline in Clinical Global Impression Scale-Severity (CGI-S) score at Day 42. The second key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the rate of PANSS responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42.
详细描述
The trial consists of a screening/tapering period, treatment period, and follow-up period. The 6-week active treatment period includes an inpatient phase and outpatient phase. Participants who complete the trial may continue treatment under a long-term extension protocol (P05689). Participants who do not continue in the treatment continuation trial (whether they complete the 6-week trial or discontinue prematurely) will have a follow-up visit 7 days after their last dose of trial medication.
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
- •Current diagnosis of schizophrenia of paranoid, disorganized, or undifferentiated subtype
- •Minimum PANSS total score of 70 at Screening and Baseline
- •Score of at least 4 (moderate) in two or more of the five items in the positive subscale of the PANSS
- •Confirmed to be experiencing an acute exacerbation of schizophrenia
- •CGI-S scale score of at least 4 (moderately ill) at Baseline
- •Has responded positively to an antipsychotic medication other than clozapine (Clozaril®) in a prior episode
排除标准
- •Body mass index (BMI) <18.5 or >40.0 kg/m^2
- •Laboratory and/or clinical evidence of clinically significant hepatic conditions
- •Known history of, or undergoing treatment for, narrow angle glaucoma
- •Diagnosed with epilepsy or has had any seizure disorder beyond childhood febrile seizures
- •Known serological evidence of human immunodeficiency virus (HIV) antibody
- •History of neuroleptic malignant syndrome or tardive dyskinesias
- •Past or current diagnosis of schizoaffective disorder, schizophrenia of residual subtype, schizophrenia of catatonic subtype, current diagnosis of schizophrenia with course specifiers continuous, single episode in partial remission, or single episode in full remission, or borderline personality disorder
研究组 & 干预措施
Olanzapine 15 mg QD
干预措施: Placebo Olanzapine (Drug)
Asenapine 2.5 mg BID
干预措施: Asenapine (Drug)
Asenapine 2.5 mg BID
干预措施: Placebo Olanzapine (Drug)
Asenapine 5 mg BID
干预措施: Asenapine (Drug)
Asenapine 5 mg BID
干预措施: Placebo Olanzapine (Drug)
Olanzapine 15 mg QD
干预措施: Placebo Asenapine (Drug)
Olanzapine 15 mg QD
干预措施: Olanzapine (Drug)
Placebo BID
干预措施: Placebo Asenapine (Drug)
Placebo BID
干预措施: Placebo Olanzapine (Drug)
结局指标
主要结局
Change From Baseline in PANSS Total Score at Day 42
时间窗: Baseline and Day 42
The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 42; improvement in symptoms is represented by negative values.
次要结局
- Change From Baseline in CGI-S Score at Day 42(Baseline and Day 42)
- Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42(Baseline and Day 42)
- Change From Baseline in Body Weight at Day 42(Baseline and Day 42)
- Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35(Baseline and Days 4, 7, 14, 21, 28 and 35)
- Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35(Days 4, 7, 14, 21, 28 and 35)
- Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)
- Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42(Days 4, 7, 14, 21, 28, 35 and 42)
- Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)
- Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)
- Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35(Baseline and Days 4, 7, 14, 21, 28 and 35)
- Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)
- Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)
- Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)
- Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)
- Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42(Baseline and Days 4, 7, 14, 21, 28, 35 and 42)