Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed Dose Study on the Efficacy of [Vortioxetine] Lu AA21004 on Cognitive Dysfunction in Adult Patients With Major Depressive Disorder (MDD)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 598
- 主要终点
- Change From Baseline to Week 8 in DSST (Number of Correct Symbols) and RAVLT (Acquisition and Delayed Recall) Using the Composite Z-score Defined as the Weighted Sum of the Individual Patient Z-scores
研究概览
简要总结
Major Depressive Disorder (MDD) is a severe and common psychiatric disorder. Although MDD primarily involves mood disturbances, patients also usually present alterations in cognitive function (attention, memory, executive functioning and psychomotor speed). Even though antidepressants are suggested in the literature to potentially improve cognitive dysfunction in patients with MDD to some degree, there is a lack of adequate and well-controlled studies to investigate this effect. This study will evaluate the efficacy, safety and tolerability of a new antidepressant Vortioxetine versus placebo on cognitive dysfunction in adult patients with MDD.
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
- •The patient is an inpatient in a psychiatric hospital or an outpatient at a psychiatric setting at the time of the study entry.
- •The patient is diagnosed with recurrent MDD according to DSM-IV-TR™ criteria (classification code 296.3x). The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
- •The patient has received prescribed treatment for a previous episode of depression.
- •The patient has a MADRS total score ≥
- •The reported duration of the current MDE is at least 3 months.
排除标准
- •The patient has a score ≥70 on the DSST (number of correct symbols), or ≥42 on the RAVLT (learning) or ≥14 on the RAVLT (memory) at the Baseline Visit.
- •The patient has any current Axis I disorder (DSM-IV-TR™ criteria) other than MDD, confirmed using the MINI.
- •The patient has a current diagnosis or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features.
- •The patient suffers from personality disorders, mental retardation, pervasive development disorder, attention-deficit/hyperactivity disorder, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
- •The patient has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
- •The patient is diagnosed with reading disability (dyslexia).
- •The patient is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide <6 months prior to the Screening Visit.
- •The patient has received electroconvulsive therapy <6 months prior to the Screening Visit.
- •The current depressive symptoms are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at the recommended dose.
- •The patient has a history of moderate or severe head trauma (for example, loss of consciousness for more than 1 hour) or other neurological disorders or systemic medical diseases that are, in the opinion of the investigator, likely to affect central nervous system functioning.
- •The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for >5 years prior to the first drug dose.
- •The patient has a clinically significant unstable illness, for example:
- •cardiovascular disease
- •seizure disorder or encephalopathy
- •congestive heart failure
- •cardiac hypertrophy
- •arrhythmia
- •bradycardia (pulse <50 bpm)
- •respiratory disease
- •hepatic impairment or renal insufficiency
- •metabolic disorder
- •endocrinological disorder
- •gastrointestinal disorder
- •haematological disorder
- •infectious disorder
- •any clinically significant immunological condition
- •dermatological disorder
- •venereal disease
- •The patient has, at the Screening Visit, an abnormal ECG that is, in the investigator's opinion, clinically significant.
- •The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.
- •The patient has previously been exposed to Vortioxetine.
- •Other protocol-defined inclusion and exclusion criteria may apply.
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Vortioxetine 10 mg
干预措施: Vortioxetine (Lu AA21004) (Drug)
Vortioxetine 20 mg
干预措施: Vortioxetine (Lu AA21004) (Drug)
结局指标
主要结局
Change From Baseline to Week 8 in DSST (Number of Correct Symbols) and RAVLT (Acquisition and Delayed Recall) Using the Composite Z-score Defined as the Weighted Sum of the Individual Patient Z-scores
时间窗: Baseline and Week 8
DSST assesses psychomotor speed of performance requiring visual perception, spatial decision-making, and motor skills. It consists of 133 digits and requires the patient to substitute each digit with a simple symbol in a 90-s period. Each correct symbol is counted, and the total score ranges from 0 (\< normal functioning) to 133 (\> normal functioning). RAVLT assesses verbal learning and memory, including immediate memory, efficiency of learning, retroactive and proactive interference effects, and encoding versus retrieval. It consists of a number of tasks, including immediate recall and delayed recall. The number of words correctly recalled on each task is recorded. The scores are standardized by subtracting the overall mean change from baseline from the individual change from baseline and dividing by the standard deviation estimate of the change from baseline. The 2 tests, DSST and RAVLT are each assigned a weight of 0.5, the 2 subtests of RAVLT are each assigned a weight of 0.25.
次要结局
- Change From Baseline to Week 8 in the TMT A (Speed of Processing)(Baseline and Week 8)
- Change From Baseline to Week 8 in MADRS Total Score(Baseline and Week 8)
- Clinical Status Using CGI-I Score at Week 8(Week 8)
- Proportion of Responders at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline(Baseline and Week 8)
- Proportion of Remitters at Week 8 (Remission is Defined as a MADRS Total Score <=10)(Week 8)
- Change From Baseline to Week 8 in DSST (Number of Correct Symbols)(Baseline and Week 8)
- Change From Baseline to Week 8 in RAVLT (Acquisition)(Baseline and Week 8)
- Change From Baseline to Week 8 in RAVLT (Delayed Recall)(Baseline and Week 8)
- Change From Baseline to Week 8 in the TMT B (Executive Function)(Baseline and Week 8)
- Change From Baseline to Week 8 in the SRT (Speed of Processing)(Baseline and Week 8)
- Risk of Suicidality Using C-SSRS Scores(Up to 8 weeks)
- Change From Baseline to Week 8 in Congruent STROOP Time to Complete (Executive Function)(Baseline and Week 8)
- Change From Baseline to Week 8 in Incongruent STROOP Time to Complete (Executive Function)(Baseline and Week 8)
- Change From Baseline to Week 8 in the CRT (Attention)(Baseline and Week 8)
- Change From Baseline to Week 8 in CGI-S Score(Baseline and Week 8)
- Change From Baseline to Week 8 Using the MADRS Total Score and the Composite Z-score(Baseline and Week 8)
- Change From Baseline to Week 1 Using the MADRS Total Score and the Composite Z-score(Baseline and Week 1)