A Phase 3, Multicenter, Double-Blind Comparison of LY2140023 and Aripiprazole in Patients With DSM-IV-TR Schizophrenia Followed by Open-Label Treatment With LY2140023
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 678
- 试验地点
- 1
- 主要终点
- Change From Baseline to 24 Weeks in Body Weight
研究概览
简要总结
The purpose of this study is to determine whether weight gain will be significantly less in LY2140023 than aripiprazole in patients with schizophrenia.
详细描述
The primary objective of this study was to test the hypothesis that mean weight gain, as assessed by change from baseline, would be statistically significantly less for flexibly dosed LY2140023 (20, 40, or 80 mg twice daily [BID]) than for flexibly dosed aripiprazole (10, 15, or 30 mg/day) in patients with schizophrenia after 24 weeks of double-blind treatment.
This was a multicenter, randomized, double-blind, Phase 3 study to assess the safety and efficacy of LY2140023 (flexibly dosed between 20 and 80 mg BID) in patients with schizophrenia. An active control, aripiprazole (flexibly dosed between 10 and 30 mg/day), was included for comparison.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Female participants of childbearing age must test negative for pregnancy at screening and agree to use single, effective, medically acceptable method of birth control
- •Participants must require initiation of or modification to current antipsychotic treatment as outpatients
- •Participants 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
- •Participants must be able to understand the nature of the study and have given their own informed consent
排除标准
- •Have been on treatment with aripiprazole in the past 2 months or are aripiprazole nonresponders
- •Participants who are pregnant, nursing, or intend to become pregnant within 30 days of completing the study
- •Hospitalized within 2 weeks of screening or have been hospitalized for an exacerbation of symptoms of schizophrenia with a discharge date in the past 2 months
- •Participants who are actively suicidal
- •Participants with uncorrected narrow-angle glaucoma, history of or current seizure disorder, uncontrolled diabetes, certain diseases of the liver, renal insufficiency, uncontrolled thyroid condition or other serious or unstable illnesses
- •Participants who have had electroconvulsive therapy (ECT) within 3 months prior to screening or will have ECT at any time during the study
- •Participants with known medical history of Human Immunodeficiency Virus positive (HIV+) status
- •Test positive for (1) Hepatitis C virus antibody or (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody
- •Participants with a corrected QT interval (Bazett's; QTcB)>450 milliseconds (msec) (male) or >470 msec (female) at screening
- •Participants who have a history of inadequate clinical response to antipsychotic treatment for schizophrenia
- •Participants who have received treatment with any depot formulation of an antipsychotic medication within 1 dosing interval, minimum of 4 weeks, prior to screening
- •Are currently enrolled in, or discontinued within the last 60 days from, a clinical trial involving an investigational product or unapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Have any other psychiatric diagnoses in addition to schizophrenia
- •Have previously completed or withdrawn from this study, or any other study investigating LY2140023 or any predecessor molecules with glutamatergic activity
- •Participants who have received an adequate treatment trial, in the opinion of the investigator, with clozapine at doses greater than 200 milligrams (mg) daily within 12 months prior to screening, or who have received any clozapine at all during the month before screening
- •Diagnosis of substance-induced psychosis within 7 days of screening (or at any time during the study)
研究组 & 干预措施
LY2140023
Double Blind Phase: 40 milligrams (mg) administered orally, given twice daily for 24 weeks. Dose may be adjusted to a minimum of 20 mg or a maximum of 80 mg. Open Label Phase: 40 mg administered orally, given twice daily for an additional 28 weeks.
干预措施: LY2140023 (Drug)
Aripiprazole
Double Blind Phase: 15 mg administered orally, given once daily for 24 weeks. Dose can be adjusted to a minimum of 10 mg or a maximum of 30 mg. Open Label Phase: LY2140023, 40 mg administered orally, given twice daily for an additional 28 weeks.
干预措施: LY2140023 (Drug)
Aripiprazole
Double Blind Phase: 15 mg administered orally, given once daily for 24 weeks. Dose can be adjusted to a minimum of 10 mg or a maximum of 30 mg. Open Label Phase: LY2140023, 40 mg administered orally, given twice daily for an additional 28 weeks.
干预措施: Aripiprazole (Drug)
结局指标
主要结局
Change From Baseline to 24 Weeks in Body Weight
时间窗: Baseline, 24 weeks
Mixed model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) mean and standard error. LS mean values were adjusted for baseline, treatment, gender, pooled investigator, visit, prior olanzapine use, treatment-by-visit interaction and baseline-by-visit interaction.
次要结局
- Percentage of Participants With Clinically Significant Weight Change(Baseline up to 24 weeks)
- Change From Baseline up to 24 Weeks in Barnes Akathisia Scale (BAS)(Baseline, 24 weeks)
- Change From Baseline up to 24 Weeks in Simpson-Angus Scale (SAS)(Baseline, 24 weeks)
- Change From Baseline up to 24 Weeks in Abnormal Involuntary Movement Scale (AIMS)(Baseline, 24 weeks)
- Change From Baseline up to 24 Weeks in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores(Baseline, 24 weeks)
- Change From Baseline up to 24 Weeks in EuroQol-5 Dimensions Questionnaire (EQ-5D) Visual Analog Scale (VAS) Health State Score(Baseline, 24 weeks)
- Schizophrenia Resource Utilization Module (S-RUM) - Number of Emergency Room (ER) or Equivalent Facility Visits and Outpatient Medical Visits(Baseline to 24 weeks)
- Schizophrenia Resource Use Module (S-RUM) - Number of Sessions With a Psychiatrist(Baseline to 24 weeks)
- Change From Baseline up to 24 Weeks in Subjective Well-Being Under Neuroleptic Treatment Scale- Short Form (SWN-SF) Total Score(Baseline, 24 weeks)
- Change From Baseline up to 24 Weeks in Personal and Social Performance (PSP) Score(Baseline, 24 weeks)
- Change From Baseline up to 24 Weeks in Clinical Global Impression-Severity Scale (CGI-S)(Baseline, 24 weeks)
- Change From Baseline up to 24 Weeks in 16-Item Negative Symptom Assessment (NSA-16)(Baseline, 24 weeks)
- Number of Participants With 30% or Greater Decrease in Positive and Negative Syndrome Scale (PANSS) Total Score(Baseline up to 24 weeks)
- Number of Participants With Suicidal Behaviors and Ideations Measured by Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline to 24 weeks)
- Time to Discontinuation(Randomization up to 24 weeks)