A Long-Term, Phase 2, Multicenter, Randomized, Open-Label Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients With DSM-IV-TR Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 261
- 试验地点
- 1
- 主要终点
- Time to Discontinuation Due to Adverse Event (AE)
研究概览
简要总结
The primary objective of this study was to assess time to discontinuation due to lack of tolerability among patients with schizophrenia receiving LY2140023, given orally twice daily for 24 weeks, versus those on atypical antipsychotic standard-of-care (SOC) treatment. Lack of tolerability was defined as discontinuation due to adverse events (AEs).
Patients who completed the active treatment phase were eligible to continue to an optional 28 weeks of treatment extension phase. This extension phase assessed key safety and efficacy measures.
详细描述
A Phase 2, multicenter, randomized, parallel, open-label study comparing the long-term safety and tolerability of LY2140023 with atypical antipsychotic agents considered to be the current SOC for patients with schizophrenia. The study included a 24-week active treatment phase and an optional 28-week active treatment extension phase.
The time to discontinuation due to AEs during Study Period III (24-week active treatment phase) was compared between LY2140023 and standard of care using the log-rank test from the Kaplan-Meier survival analysis. Patients who completed Study Period III or who discontinued for a reason other than AEs were considered as censored observations.
Secondary objectives were assessed during both Study Period III [Active Treatment Phase] and Study Period IV [Active Treatment Extension Phase]) except for treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), electroencephalograms (EEGs), electrocardiograms (ECGs) (analysis for Study Period III only) (indicated in "Time Frame" in "Results" section)
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
- Single (Outcomes Assessor)
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
- •Clinical diagnosis of schizophrenia
- •Patients, in the investigator's opinion, must require a switch to another antipsychotic medication as clinically indicated or initiation of an antipsychotic agent
- •Patients must be willing and able to be hospitalized, or to remain hospitalized (if already hospitalized), for up to 17 days
- •The investigator expects, at the time of enrollment, that the patient will be able to be discharged from the hospital after the first 2 weeks of active treatment
- •Disease symptoms must meet a certain range as assessed by the clinician
- •Patients must have evidence of functional impairment (i.e. social or vocational deficiency)
- •Patients must be considered reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol, and be willing to perform all study procedures
- •Patients must be able to understand the nature of the study and have given their informed consent
排除标准
- •Patients who are actively suicidal
- •Patients who are pregnant or nursing
- •Patients who have had electroconvulsive therapy (ECT) within 3 months of screening or who will have ECT at any time during the study
- •Patients with uncorrected narrow-angle glaucoma, seizures, uncontrolled diabetes, certain diseases of the liver, uncontrolled thyroid condition or other serious or unstable illnesses
- •Patients with Parkinson's disease, psychosis related to dementia or related disorders
- •Patients with known Human Immunodeficiency Virus positive (HIV+) status
研究组 & 干预措施
LY2140023
LY2140023 (80 mg/day), given orally twice daily as two 40-mg tablets for 24 weeks
干预措施: LY2140023 (Drug)
aripiprazole
aripiprazole (20 mg/day), given orally once daily for 24 weeks
干预措施: aripiprazole (Drug)
olanzapine
olanzapine (15 mg/day), given orally once daily for 24 weeks
干预措施: olanzapine (Drug)
risperidone
risperidone (4 mg/day), given orally, once or BID for 24 weeks
干预措施: risperidone (Drug)
结局指标
主要结局
Time to Discontinuation Due to Adverse Event (AE)
时间窗: Baseline through 24 weeks
次要结局
- Number of Participants With Shift From Baseline to Maximum Post-Baseline Grading in Electroencephalograms (EEGs)(Baseline through 52 weeks)
- Number of Participants With Potentially Clinically Significant Changes in QT Intervals Electrocardiograms (ECGs)(Baseline through 24 weeks)
- Change From Baseline in Positive and Negative Syndrome Scale (PANSS) at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in 16-Item Negative Symptoms Assessment (NSA-16) Total Score at 52 Weeks Endpoint(Baseline, 52 weeks)
- Percentage of Participants With Remission (Rate of Remission) at Week 24 Endpoint(24 weeks)
- Change From Baseline in Blood Pressure (BP) at 52 Weeks Endpoint(Baseline, 52 weeks)
- Number of Participants With Potentially Clinical Significant Change in Fasting Glucose Level(Baseline through 52 weeks)
- Number of Participants With Potentially Clinical Significant Change in Lipids Level(Baseline through 52 weeks)
- Number of Participants With Treatment-Emergent Change in Neurological Examination(Baseline through 52 weeks)
- Change From Baseline in Pulse Rate at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 52 Weeks Endpoint(Baseline, 52 weeks)
- Percentage of Participants With Response (Rate of Response) at 6 and 24 Weeks Endpoints(6 and 24 weeks)
- Percentage of Participants With Relapse (Rate of Relapse)(Baseline through 52 weeks)
- Change From Baseline in Personal and Social Performance (PSP) at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in Weight at 52 Weeks Endpoint(Baseline, 52 weeks)
- Number of Participants With Suicidal Behaviors and Ideations Baseline Through 52 Weeks(Baseline through 52 weeks)
- Change From Baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB): Overall Composite T-Score at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in University of California-San Diego (UCSD) Performance-Based Skills Assessment-B (UPSA-B) Total Score at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in Number of Psychiatric Visits at 24 Weeks Endpoint(Baseline, 24 weeks)
- Change From Baseline in Subjective Well-Being Under Neuroleptic Treatment-Short Form (SWN-S) Total Score at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in EuroQoL Questionnaire-5 Dimension (EQ-5D) at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in Barnes Akathisia Scale (BAS) Global Score at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at 52 Weeks Endpoint(Baseline, 52 weeks)
- Change From Baseline in Simpson-Angus Scale (SAS) Total Score at 52 Weeks Endpoint(Baseline, 52 weeks)