A Study to Assess the Long-Term Efficacy and Safety of Olanzapine and Fluoxetine Combination Versus Fluoxetine Only in the Relapse Prevention of Stabilized Patients With Treatment-Resistant Depression
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 892
- 试验地点
- 1
- 主要终点
- Time to Relapse by Any Criteria
研究概览
简要总结
The purpose of this study is to determine whether olanzapine and fluoxetine combination (OFC) if used for a long time (47 weeks) makes patients suffering from Treatment Resistant Depression stable, determine if OFC is safe when used to treat patients with Treatment Resistant Depression for a long time (up to 47 weeks), to determine whether olanzapine and fluoxetine combination or fluoxetine alone is better to treat Treatment Resistant Depression when treated for a long time (up to 47 weeks) and to assess the quality of life during treatment.
详细描述
This is a multicenter, randomized, double-blind, active comparator-controlled, parallel study of participants with Treatment Resistant Depression (TRD), comparing the efficacy and safety of olanzapine and fluoxetine Combination (OFC) versus fluoxetine in relapse prevention of stabilized participants with TRD. The study will consist of 4 phases: a screening phase; a 6- to 8-week open-label acute treatment phase; a 10- to 12-week open-label stabilization phase; and a 27- to 29-week double-blind relapse prevention treatment phase. Participants who demonstrate response to open-label OFC during the acute treatment phase will continue into the stabilization phase. Participants who remain stable while receiving open-label OFC during this phase will be randomized to receive either OFC or fluoxetine during the double-blind relapse prevention phase. Investigators and participants will be blinded to the precise duration of the stabilization period, the definition of remission, and the criteria for entry into the relapse prevention phase; this information is described in a supplement given to Ethical Review Boards (ERBs) and regulatory authorities.
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
- Triple (Participant, 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, confirmed by the structured clinician Interview for DSM-IV Axis 1 disorders (SCID-I).
- •If female and of childbearing potential, test negative for pregnancy and agree to abstain from sexual activity or use a medically accepted means of contraception during the study. Use of any oral or injectable contraception must be initiated prior to receiving treatment.
- •Have 17-item Hamilton Depression (HAM-D) score greater than or equal to 18 at screening and the day treatment is due to be received for the first time.
- •Have treatment-resistant depression, as defined by having demonstrated failure to achieve satisfactory antidepressant response to adequate separate treatment courses of at least 2 different antidepressants within the current episode of MDD.
排除标准
- •Have a diagnosis of Parkinson's disease or related disorders.
- •Have a current or lifetime diagnosis of any of the following according to DSM-IV 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 current diagnosis of post-partum depression, MDD with atypical features, or MDD with a seasonal pattern as defined in the DSM-IV.
- •Have paranoid, schizoid, schizotypal, antisocial, and borderline personality disorders (Axis II) as a comorbid or primary diagnosis, based on DSM-IV criteria.
- •Have had psychotic symptoms within 1 month prior to Screening or demonstrate psychotic features at screening and on the day treatment is due to be assigned for the first time as determined by the investigator.
- •Have DSM-IV substance dependence/abuse or not willing to avoid use of the substance (not including dependence on nicotine or caffeine), as defined by the SCID-I, within the past 30 days.
- •Are actively suicidal in the judgment of the investigator.
- •Have had one or more seizures without a clear and resolved etiology.
- •Have leukopenia or history of leukopenia without a clear and resolved etiology, or known history of agranulocytosis during the participant's lifetime.
- •Have alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) values greater than or equal to 2 times the upper limit of normal (ULN) of the performing laboratory or aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) values greater than or equal to 2 times the ULN or total bilirubin values greater than or equal to 1.5 times the ULN at any time during screening.
- •Have acute, serious, or unstable medical conditions.
- •Have any illness such that death is anticipated within 1 year or intensive care unit hospitalization for the illness is anticipated within 6 months.
- •Have elevated prolactin levels at screening.
- •Have Bazett's corrected QT interval (QTc) greater than 450 milliseconds (male) or greater than 470 milliseconds (female) at screening and when treatment is due to be received for the first time.
- •Have received electroconvulsive therapy (ECT) or vagus nerve stimulation (VNS) treatment within the current episode; have a history of failure to adequate treatment courses of ECT or VNS; or will require ECT or VNS at any time during study participation.
- •If receiving psychotherapy, light therapy, or both, are anticipated to require changes in frequency/intensity of treatment regimen or to cease treatment regimen over the duration of the study. Participants who are not receiving any of these therapies upon study entry may not begin any of these therapies during screening, or during any treatment phases of the study.
- •Have received previous treatment with clozapine.
- •Have used a monoamine oxidase inhibitor (MAOI) within 14 days prior to screening or are expected to need MAOI treatment at any time during this study through 5 weeks after the participant discontinues from the study.
研究组 & 干预措施
Olanzapine and Fluoxetine combination (OFC)
干预措施: Olanzapine and Fluoxetine combination (OFC) (Drug)
Fluoxetine
干预措施: Fluoxetine (Drug)
结局指标
主要结局
Time to Relapse by Any Criteria
时间窗: Randomization (Week 20) to Week 47
Relapse defined as meeting any of these criteria: 50% increase in Montgomery-Asberg Depression Rating Scale (MADRS) score from randomization with a Clinical Global Impressions-Severity (CGI-S) of Depression score increase to a score of 4 or more; Hospitalized for depression or suicidality; Discontinued due to lack of efficacy/worsening of depression/suicidality. MADRS is a 10-item rating scale for depressive mood symptoms severity, items rated on 0-6 scale, with total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). CGI-S measures severity of illness at time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (the most extremely ill). Lack of Efficacy/Worsening of depression was at discretion of investigator based on clinical observation. Suicidality is thoughts or actions of self-harm as determined by the investigator. Those who did not relapse were "censored" at their last observation.
次要结局
- Percentage of Participants Maintaining Response at Any Point During Stabilization Treatment Phase(Week 8 to Week 20)
- Percentage of Participants Achieving Remission at Any Point During Stabilization Treatment Phase(Week 8 to Week 20)
- Percentage of Participants Who Relapse by Any Criteria(Randomization (Week 20) to Week 47)
- Percentage of Participants Who Relapse Based on Montgomery-Åsberg Depression Rating Scale (MADRS) Score With Concomitant Clinical Global Impressions-Severity (CGI-S) of Depression Score(Randomization (Week 20) to Week 47)
- Percentage of Participants Who Relapse as Measured by Hospitalization for Depression or Suicidality(Randomization (Week 20) to Week 47)
- Percentage of Participants Who Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality(Randomization (Week 20) to Week 47)
- Time to Relapse Based on the Montgomery-Åsberg Depression Rating Scale (MADRS) Score With Concomitant Clinical Global Impressions-Severity (CGI-S) of Depression Score(Randomization (Week 20) to Week 47)
- Time to Relapse as Measured by Hospitalization for Depression or Suicidality(Randomization (Week 20) to Week 47)
- Time to Relapse as Measured by Discontinuation Due to Lack of Efficacy/Worsening of Depression/Suicidality(Randomization (Week 20) to Week 47)
- Percentage of Participants Responding to Treatment During Open-Label Acute Treatment Phase(Week 0 to Week 8)
- Percentage of Participants Maintaining Remission(Randomization (Week 20) to Week 47)
- Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Mixed-Effects Model Repeated Measures (MMRM) Analysis(Randomization (Week 20), Week 47)
- Mean Change From Week 20 to Week 47 in Montgomery-Asberg Depression Rating Scale (MADRS) Using Last Observation Carried Forward (LOCF) Analysis(Randomization (Week 20), up to Week 47)
- Mean Change From Week 20 to Week 47 in Clinical Global Impressions - Severity (CGI-S) of Depression Using Mixed-Effects Model Repeated Measures (MMRM) Analysis(Randomization (Week 20), Week 47)
- Resource Utilization - Average Number of Hours Worked for Pay Per Week at Week 47(Week 47)
- Resource Utilization (Number of Psychiatric Visits, Number of Emergency Room or Equivalent Facility Visits for Psychiatric Illness)(Randomization (Week 20) to Week 47)
- Change From Week 20 to Week 47 Endpoint in the Sheehan Disability Scale (SDS)(Randomization (Week 20), up to Week 47)
- Percent of Participants With Treatment-Emergent Akathisia(Randomization (Week 20) to Week 47)
- Percent of Participants With Treatment-Emergent Parkinsonism(Randomization (Week 20) to Week 47)
- Percent of Participants With Treatment-Emergent Dyskinesia(Randomization (Week 20) to Week 47)
- Mean Change From Week 20 to Week 47 in Fasting Total Cholesterol(Randomization (Week 20), Week 47)
- Percent of Participants With Treatment-Emergent High Fasting Total Cholesterol(Randomization (Week 20) to Week 47)
- Mean Change From Week 20 to Week 47 in Fasting Low-Density Lipoprotein (LDL) Cholesterol(Randomization (Week 20), Week 47)
- Percent of Participants With Treatment-Emergent High Fasting Low-Density Lipoprotein (LDL) Cholesterol(Randomization (Week 20) to Week 47)
- Mean Change From Week 20 to Week 47 in Fasting High-Density Lipoprotein (HDL) Cholesterol(Randomization (Week 20), Week 47)
- Percent of Participants With Treatment-Emergent Low Fasting High-Density Lipoprotein (HDL) Cholesterol(Randomization (Week 20) to Week 47)
- Percent of Participants With Treatment-Emergent Hepatic Events(Randomization (Week 20) to Week 47)
- Mean Change From Week 20 to Week 47 in Fasting Triglycerides(Randomization (Week 20), Week 47)
- Percent of Participants With Treatment-Emergent High Fasting Triglycerides(Randomization (Week 20) to Week 47)
- Mean Change From Week 20 to Week 47 in Fasting Glucose(Randomization (Week 20), Week 47)
- Percent of Participants With a 60 Milliseconds (Msec) Increase in Fridericia-Corrected (for Rate) Cardiac QT Interval (QTcF) on Electrocardiogram(Randomization (Week 20) to Week 47)
- Percent of Participants With Treatment-Emergent High Fasting Glucose(Randomization (Week 20) to Week 47)
- Mean Change From Week 20 to Week 47 in Weight(Randomization (Week 20), Week 47)
- Percent of Participants With Week 20-to-Week 47 Endpoint Increase in Weight of at Least 7%(Week 20 to Week 47)
- Percent of Participants With Suicide-Related Thoughts and Behaviors(Randomization (Week 20) to Week 47)
- Mean Change in Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) on Electrocardiogram(Randomization (Week 20), Week 47)
- Percent of Participants With Treatment-Emergent Corrected (for Rate) Cardiac QT Interval Using Fridericia's Formula (QTcF) on Electrocardiogram ≥500 Milliseconds (Msec)(Randomization (Week 20) to Week 47)