A Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study of 3 Doses of LY2140023 Monohydrate in the Acute Treatment of Patients With DSM-IV-TR Schizophrenia
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 567
- 试验地点
- 1
- 主要终点
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score
研究概览
简要总结
The purpose of this study is to determine whether at least 1 dose level of LY2140023 given to acutely ill patients with schizophrenia will demonstrate significantly greater efficacy as compared to placebo.
详细描述
The primary objective of this study was to test the hypothesis that at least 1 dose level of LY2140023, given orally to patients with schizophrenia at doses of 80 mg twice daily (BID), 40 mg BID, or 10 mg BID, would demonstrate significantly greater efficacy than placebo at Visit 9, as measured by the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score.
This was a multicenter, randomized, double-blind, parallel, fixed-dose, Phase 3 study in patients with schizophrenia. The study consisted of 3 periods: a screening and antipsychotic taper phase, a 7-day placebo lead-in phase that was blinded to investigators and patients, and a 6-week active treatment phase.
Eligible patients were those for whom a modification of antipsychotic medication was acutely indicated, in the opinion of the investigator. To be included in the study, patients must have experienced an exacerbation of their illness within the 2 weeks prior to study entry, leading to an intensification of the level of psychiatric care.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR); and confirmed by the Structured Clinical Interview for DSM-IV-TR (SCID)
- •Non pregnant female patients who agree to use acceptable birth control
- •Participants must be considered moderately ill in the opinion of the investigator
- •Patients in whom a modification of antipsychotic medication or initiation of antipsychotic medication is acutely indicated in the opinion of the investigator
- •Willing to participate in a minimum of 2 weeks of inpatient hospitalization
- •One year history of Schizophrenia prior to entering the study
- •At study entry patients with a history of antipsychotic treatment must have a lifetime history of at least one hospitalization for the treatment of schizophrenia, not including the hospitalization required for study. Patients who have never taken antipsychotic treatment may enter the study even without a history of hospitalization.
- •At study entry patients with a history of antipsychotic treatment must have a history of at least one episode of illness exacerbation requiring an intensification of treatment intervention or care in the last 2 years, not including the present episode of illness. Patients who have never taken antipsychotic treatment may enter the study without a past history of illness exacerbation and intensification of treatment in the last 2 years.
- •At study entry patients must have experienced an exacerbation of illness within the 2 weeks prior to entering the study, leading to an intensification of psychiatric care in the opinion of the investigator. If exacerbation occurs in patients who are presently hospitalized, the patient must not have been hospitalized longer than 60 days at entry of the study.
- •Patients must be considered reliable and have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures
排除标准
- •Patients who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia
- •Diagnosis of substance dependence or substance abuse within 6 month of study entry
- •Diagnosis of substance-induced psychosis within 7 days of study entry
- •Currently enrolled in, or discontinued within 6 months from a clinical trial involving an investigational product or unapproved use of a drug or device
- •Participated in any clinical trial with any pharmacological treatment intervention for which they received a study-related medication in the 6 months prior to study entry
- •Previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity
- •Treatment with clozapine at doses greater than 200 mg daily within 12 months prior to entering the study, or who have received any clozapine at all during the month before study entry
- •Patients currently receiving treatment (within 1 dosing interval, minimum of 4 weeks, prior entering the study) with a depot formulation of an antipsychotic medication
- •Patients who are currently suicidal
- •Females who are pregnant, nursing, or who intend to become pregnant within 30 days of completing the study
- •Patients with uncorrected narrow-angle glaucoma, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses
- •Have a history of one or more seizures
- •Electroconvulsive therapy (ECT) within 3 months of entering the study or who will have ECT at any time during the study
- •History of low white blood cell count
- •Medical history of Human Immunodeficiency Virus positive (HIV+) status.
- •Higher than normal blood prolactin levels
- •Abnormal electrocardiogram results
研究组 & 干预措施
80 milligrams (mg) LY2140023, BID
An 80-mg LY2140023 tablet administered orally, twice daily (BID) for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time placebo tablets identical to LY2140023 are administered orally, BID.
干预措施: LY2140023 (Drug)
40 mg LY2140023, BID
A 40-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID.
干预措施: LY2140023 (Drug)
10 mg LY2140023, BID
A 10-mg LY2140023 tablet administered orally, BID for 6 weeks. Prior to randomization, participants will complete a 1-week placebo lead-in period, during which time, placebo tablets identical to LY2140023 are administered orally, BID.
干预措施: LY2140023 (Drug)
Placebo
A placebo tablet administered orally, BID for 7 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score
时间窗: Baseline, Week 6
The PANSS scale assessed participants (pts) for positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consisted of 30 items. Each item was rated from 1 (absence of symptoms) to 7 (symptoms extremely severe). The sum of the 30 items was defined as the PANSS total score and ranged from 30 to 210. The least squares (LS) mean was estimated using a mixed-effects model with repeated measures (MMRM) that included the fixed, categorical effects of treatment, pooled investigative site, visit, treatment-by-visit interaction, gender, and predefined subpopulation ('yes/no'), as well as the continuous, fixed covariates of baseline score and baseline score-by-visit interaction.
次要结局
- Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale(Baseline, Week 6)
- Change From Baseline in Abnormal Involuntary Movement Scales (AIMS) 1-7 Total Score(Baseline, Week 6)
- Change From Baseline in the 16-Item Negative Symptoms Assessment (NSA-16) Total Score(Baseline, Week 6)
- Change From Baseline on Subjective Well-Being Under Neuroleptic Treatment Scale - Short Form (SWN-S) Total Score(Baseline, Week 6)
- Number of Participants Who Discontinued(Randomization up to Week 6)
- Time to Discontinuation(Randomization up to Week 6)
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in a Predefined Subpopulation of Schizophrenia Participants(Baseline, Week 6)
- Change From Baseline in the Personal and Social Performance (PSP) Score in a Predefined Subpopulation(Baseline, Week 6)
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Subscores(Baseline, Week 6)
- Percentage of Participants Who Are Responders(Baseline, Week 6)
- Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Sessions With a Psychiatrist(Baseline and Week 6)
- Change From Baseline in Barnes Akathisia Scale (BAS) Global Score(Baseline, Week 6)
- Change From Baseline on the European Quality of Life-5 Dimension (EQ-5D) Questionnaire(Baseline, Week 6)
- Change From Baseline in the Personal and Social Performance (PSP) Score(Baseline, Week 6)
- Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score in Females(Baseline, Week 6)
- Time to Response(Baseline up to Week 6)
- Change From Baseline in Weight(Baseline, Week 6)
- Change From Baseline on Schizophrenia Resource Utilization Module (S-RUM): Emergency Room (ER) Visits and Outpatient Visits(Baseline and Week (Wk) 6)
- Percentage of Participants With a Change From Baseline in Suicidal Behaviors and Ideations Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline up to Week 6)
- Change From Baseline in Prolactin(Baseline, Week 6)
- Change From Baseline in Simpson-Angus Scale (SAS) Total Score(Baseline, Week 6)