A Study to Assess the Short-Term Efficacy and Safety of Olanzapine and Fluoxetine Compared to Placebo and Fluoxetine for Nonpsychotic Treatment-Resistant Depression
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 176
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline to 8 Week Endpoint in Montgomery-Äsberg Depression Rating Scale (MADRS)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of olanzapine and fluoxetine compared to placebo and fluoxetine as treatment for treatment-resistant depression (TRD) in Chinese participants.
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
- •Have single or recurrent unipolar major depressive disorder (MDD) without psychotic features by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) clinical assessment
- •Have a total score ≥22 on the 17-item Hamilton Depression Rating Scale (HAM-D17) at screening and randomization
- •Have treatment-resistant depression (TRD), defined as having failed to achieve a satisfactory antidepressant response, in the opinion of the investigator, to separate treatment courses of at least 2 different antidepressants, other than fluoxetine, of adequate dosage and duration (≥6 weeks) within the current major depressive episode
排除标准
- •Have a diagnosis of Parkinson's disease or a related disorder
- •Have a current or lifetime diagnosis of any of the following conditions, according to DSM-IV-TR criteria: Schizophrenia; Schizophreniform Disorder; Schizoaffective Disorder; Delusional Disorder; Psychotic Disorder Not Otherwise Specified; Bipolar Disorder I or II; Delirium of any type; Dementia of any type; Amnestic Disorder; any Substance-Induced Disorder; or any Psychotic Disorder due to a General Medical Condition
- •Have a current diagnosis of post-partum depression or MDD with a seasonal pattern as defined in the DSM-IV-TR
- •Have paranoid, schizoid, schizotypal, antisocial, or borderline personality disorder (Axis II) as a comorbid or primary diagnosis, based on DSM-IV-TR criteria
- •Have DSM-IV-TR substance dependence/abuse or are not willing to avoid use of the substance (not including dependence on nicotine or caffeine) within 30 days of screening
- •Are actively suicidal in the judgment of the investigator
- •Have uncorrected narrow-angle glaucoma
- •Have had one or more seizures without a clear and resolved etiology
- •Have leukopenia
- •Have any acute, serious, or unstable medical conditions
- •Have an increased serum prolactin concentration at screening
- •Have a rate-corrected cardiac QT interval, calculated using Bazett's formula (QTc Bazett's [Rate-corrected cardiac QT interval on electrocardiogram calculated using Bazett's formula(QTcB)]), on Electrocardiogram (ECG) >450 milliseconds (male) or >470 milliseconds (female) at screening
- •Have a history of allergic reaction to olanzapine, fluoxetine, or olanzapine in combination with fluoxetine
- •Have had treatment with olanzapine, fluoxetine, or olanzapine in combination with fluoxetine withdrawn due to clinically significant and/or intolerable adverse effects within 6 months of screening
- •Have received treatment with remoxipride within 6 months of randomization
- •Have received treatment with depot antipsychotics within one dosing interval before randomization
- •Have received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS) treatment within the current MDD episode, or has a history of failure to respond to adequate treatment courses of ECT or VNS, or is expected to require ECT or VNS at any time during the study
- •Have received previous treatment with clozapine
- •Have received treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of screening, or are expected to need MAOI treatment at any time during the study or up until 5 weeks after study discontinuation
研究组 & 干预措施
Olanzapine + Fluoxetine
Olanzapine starting dose is 5 milligram (mg) (1 tablet). May titrate up to 10 mg (2 tablets), or 15 mg (3 tablets) administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
干预措施: Olanzapine (Drug)
Olanzapine + Fluoxetine
Olanzapine starting dose is 5 milligram (mg) (1 tablet). May titrate up to 10 mg (2 tablets), or 15 mg (3 tablets) administered once daily by mouth for 8 weeks.
Fluoxetine starting dose is 20 mg. May titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
干预措施: Fluoxetine (Drug)
Placebo + Fluoxetine
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
干预措施: Fluoxetine (Drug)
Placebo + Fluoxetine
Placebo matches the Olanzapine tablet for blinding.
Fluoxetine starting dose is 20 mg, then may titrate up to 40 mg or 50 mg administered once daily by mouth for 8 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change From Baseline to 8 Week Endpoint in Montgomery-Äsberg Depression Rating Scale (MADRS)
时间窗: Baseline, 8 Weeks
The MADRS total score is the sum of the 10 items; therefore the possible MADRS total score ranges from 0 to 60. A higher MADRS total score indicates a greater severity of depressive symptoms. Least square means (LSM) change from baseline, standard error was derived using mixed model repeated measures (MMRM) methodology with factors for treatment, Pooled Investigator, Visit, (Baseline + Treatment)\*Visit.
次要结局
- Mean Change From Baseline to 8 Week Endpoint in the Simpson-Angus Scale (SAS)(Baseline, 8 Weeks)
- Percentage of Participants Who Achieve Remission Based on MADRS Total Score ≤10 at 8 Weeks(Baseline, 8 Weeks)
- Mean Change From Baseline to 8 Week Endpoint in Clinical Global Impressions-Severity of Depression (CGI-S) Scale(Baseline, 8 Weeks)
- Mean Change From Baseline to 8 Week Endpoint in the Sheehan Disability Scale (SDS)(Baseline, 8 Weeks)
- Mean Change From Baseline to 8 Week Endpoint in the Abnormal Involuntary Movement Scale (AIMS)(Baseline, 8 Weeks)
- Mean Change From Baseline to 8 Week Endpoint in the Short-Form 36 Health Survey (SF-36)(Baseline, 8 Weeks)
- Percentage of Participants Who Achieve a Response Based on a ≥50% Reduction From Baseline in MADRS Total Score(Baseline,8 Weeks)
- Mean Change From Baseline to 8 Week Endpoint in the Barnes Akathisia Scale (BAS)(Baseline, 8 Weeks)