A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-653 in the Treatment of Subjects With Treatment-Resistant Depression
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Cohort 1: Time to Relapse of Depressive Symptoms Postdose as Measured by Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of TAK-653 compared with placebo in maintaining the effect of ketamine treatment on depressive symptoms.
详细描述
The drug being tested in this study is called TAK-653. TAK-653 is being tested to treat people who have depression and have not responded to several treatments (treatment-resistant depression).
This study will look at the efficacy and safety of TAK-653 in participants with treatment-resistant depression who take TAK-653 in addition to standard care.
The study will enroll approximately 90 patients. Participants who meet the study entry criteria will be assessed for response to ketamine by administering 2 intravenous (IV) infusions of ketamine (0.5 mg/kg given over 40 minutes; maximum dose 40 mg/day) on Day -5 (±1) and Day -1 (±1). To determine response to ketamine, the Day -5 predose Montgomery Åsberg Depression Rating Scale (MADRS) total score (before the first ketamine infusion) will be compared with the MADRS total score predose on Day 1 (24 hours after the second ketamine infusion on Day -1). Two cohorts (ketamine responders and ketamine nonresponders) of participants will be enrolled in parallel into the study.
Participants will then be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups - which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- TAK-653
- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.
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
- •Has a primary diagnosis of major depressive disorder (MDD), without psychotic features, according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) criteria, as assessed by a board-certified psychiatrist. MDD should be the principal diagnosis and the condition that best accounts for the clinical presentation. Participants with a secondary diagnosis of generalized anxiety disorder or social anxiety disorder may be included if, in the principal investigator's judgment, such diagnosis will not interfere with participation in the study or with outcome assessments. The diagnostic assessment must include a face-to-face evaluation of the participant using the Mini International Neuropsychiatric Interview (MINI).
- •Has MDD that is resistant to treatment (i.e., TRD), defined as failure to respond to at least 2, but not more than 5, adequate trials of pharmacological treatment in the current episode, as determined using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH ATRQ).
- •Qualifies as a candidate for receiving ketamine infusions as a treatment for their depression, in the opinion of the investigator.
- •Is naive to ketamine treatment.
- •Has a Hamilton Depression Rating Scale-17 (HAMD-17) total score of ≥22 at Screening.
- •Is on stable pharmacological treatment for depression (≤50% change in dose) during the last 6 weeks prior to Randomization. Participants who are not currently taking pharmacological treatment for depression may be eligible, with the approval of the medical monitor.
排除标准
- •The participant or any immediate family member has a seizure disorder or a history of seizure disorder, except febrile convulsions.
- •Is currently diagnosed with a personality disorder, dementia, eating disorder, schizophrenia, schizoaffective disorder, or bipolar disorder.
- •Has a history of neurological abnormalities that is judged by the medical monitor to preclude the participant's participation in the study; or brain injury including traumatic injury, perinatal encephalopathy, and postnatal brain damage, blood-brain barrier abnormality, and cavernous angioma.
- •Has a history of cerebral arteriosclerosis.
- •Is currently diagnosed with glaucoma.
- •Is at an imminent risk of suicide per the Columbia - Suicide Severity Rating Scale (C-SSRS) (score of 5) or per the investigator's clinical judgment.
- •Has uncontrolled hypertension or a systolic blood pressure of >150 millimeter of mercury (mm Hg) or diastolic blood pressure >95 mm Hg at Screening.
- •Has a positive urine test result for drugs of abuse (defined as any illicit drug use) at Screening or Day
- •Has a blood alcohol content of ≥0.06% at Screening, prior to ketamine infusion (Day -5 or Day -1), or Day
- •Is currently diagnosed with abuse of or dependence on alcohol or other drugs (except nicotine). The participant will be allowed to enroll if his/her drug and alcohol abuse/dependence is in full (complete, not partial) sustained (>1 year) remission.
- •Has any contraindication to the administration of ketamine.
研究组 & 干预措施
Cohort 1 (Ketamine Responders): TAK-653 6 mg
TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 1 and 2; followed by TAK-653 tablets, orally, once daily on Days 3 and 4; followed by TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 5 to 7; followed by TAK-653 tablets, orally, once daily on Days 8 to 56.
干预措施: TAK-653 (Drug)
Cohort 1 (Ketamine Responders): TAK-653 6 mg
TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 1 and 2; followed by TAK-653 tablets, orally, once daily on Days 3 and 4; followed by TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 5 to 7; followed by TAK-653 tablets, orally, once daily on Days 8 to 56.
干预措施: Placebo (Drug)
Cohort 1 (Ketamine Responders): Placebo
TAK-653 placebo-matching tablets, orally, once daily up to Day 56
干预措施: Placebo (Drug)
Cohort 2 (Ketamine Nonresponders): TAK-653 6 mg
TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 1 and 2; followed by TAK-653 tablets, orally, once daily on Days 3 and 4; followed by TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 5 to 7; followed by TAK-653 tablets, orally, once daily on Days 8 to 56.
干预措施: TAK-653 (Drug)
Cohort 2 (Ketamine Nonresponders): TAK-653 6 mg
TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 1 and 2; followed by TAK-653 tablets, orally, once daily on Days 3 and 4; followed by TAK-653 tablets plus TAK-653 placebo-matching tablets, orally, once daily on Days 5 to 7; followed by TAK-653 tablets, orally, once daily on Days 8 to 56.
干预措施: Placebo (Drug)
Cohort 2 (Ketamine Nonresponders): Placebo
TAK-653 Placebo-matching tablets, orally, once daily up to Day 56
干预措施: Placebo (Drug)
结局指标
主要结局
Cohort 1: Time to Relapse of Depressive Symptoms Postdose as Measured by Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
时间窗: Baseline up to Day 57
The MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms. Items are rated on scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).
次要结局
- Cohort 1: Change from Baseline in Clinical Global Impression-Severity Scale (CGI-S) Score at the End of Each Week of Treatment(Baseline and weekly up to Day 57)
- Cohort 1: Change From Baseline in Quick Inventory of Depressive Symptomatology-16 Item (QIDS-SR16) Total Score at the End of Each Week of Treatment(Baseline and weekly up to Day 57)
- Cohort 1: Percentage of Participants who Meet the Markedly Abnormal Criteria for Vital Signs Measurement at Least Once Postdose(Baseline up to Day 78)
- Cohort 1: Percentage of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Postdose(Baseline up to Day 78)
- Cohort 1: Percentage of Participants who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Postdose(Baseline up to Day 78)
- Cohort 1: Change from Baseline in MADRS Total Score at the End of Each Week of Treatment(Baseline and weekly up to Day 57)
- Cohort 1: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Day 78)
- Cohort 1: Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs) that Led to Study Drug Discontinuation(Baseline up to Day 78)