NCT03965871已完成2 期
A Multicentre, Double-blind, Randomised, Placebo - Controlled Phase II Study to Assess Efficacy, Safety and Pharmacokinetics of Inhaled Esketamine in Subject With Treatment-resistant Bipolar Depression
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 88
- 试验地点
- 11
- 主要终点
- Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Day 14
研究概览
简要总结
The purpose of the study is to determine the efficacy, safety and pharmacokinetics of inhaled Esketamine in participants with treatment-resistant bipolar depression (TRBD). The study is to determine the efficacy and dose response of three Esketamine doses, compared with placebo.
详细描述
This is a randomized, multiple dose, placebo-controlled, double-blind, multicentre study of Esketamine DPI, inhalation powder delivered via dry powder inhaler (DPI) in participants with TRBD. There are 3 study phases: Screening phase, a two weeks double-blind treatment phase and a 6-week follow-up phase. Participants are to be randomized in 1:1:1:1 ratio to receive placebo or one of the three doses of Esketamine DPI. Participants from each group will receive different dosing sequences, consider as a single dose, corresponding to low, medium, high Esketamine dose or placebo. Participants will undergo one cycle of treatment consisting of four doses of Esketamine DPI or placebo over 14-day period. Participants safety will be monitored throughout the study.
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
- •Gender: female or male,
- •Age: 18 - 65 years old, inclusive, on the day of Screening,
- •Participant must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for depressive episode in Bipolar Disorder (BD) type I or II, without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI),
- •Participant must have in Montgomery-Asberg Depression Rating Scale (MADRS) total score of >= 24 at Screening and predose on Day 1,
- •Participant is treatment resistant in the current episode of depression, defined as having an inadequate response to at least 2 adequate mood stabilizing treatment regimens administered for the sufficient duration and dose and administered in the current episode of depression,
- •Participant in the last mood stabilizing treatment regimen is to be administered at least one of the medication listed in the protocol,
- •Participant's last mood stabilizing treatment regimen is to be without antidepressant drugs from the class: SSRI, SNRI, TCA, MAOI or NaSSA,
- •Participant must be on stable mood stabilizing treatment regimen (listed in the protocol), remain non-responsive to it and continue the treatment from Screening to at least the duration of the double-blind treatment phase,
- •Participant's other drugs taken as a standard treatment for bipolar disorder, but not for depressive episode treatment, are to be allowed and may be continued through the study and it's administration is up to Investigator discretion,
- •Participant agrees to be hospitalized voluntarily for a period of 12 h before first administration and until the end of treatment phase on Day 14,
- •Participant must be medically stable on the basis of clinical laboratory tests, physical examination, vital signs, 12-lead ECG,
- •Participant agrees to blood sample collection for DNA analysis,
- •Participant of childbearing potential willing to use acceptable forms of contraception.
排除标准
- •Participant has a current DSM-5 diagnosis, according to MINI, of any other than BD disorder,
- •Participant has a BD with a rapid-cycling course (≥ 4 episodes per year),
- •Participant has in Young Mania Rating Scale (YMRS) total score of greater than 12 at Screening and every other assessment,
- •Participant has suicidal ideation in MADRS 'suicidal thoughts' subscale score greater or equal to 2 and/or in C-SSRS score greater or equal to 4 at Screening and/or has a history of suicidal thoughts within 6 months prior to Screening and/or history of suicidal attempt within 1 year prior to Screening,
- •Participant has a history or current signs and symptoms of chronic obstructive pulmonary disease (COPD), asthma, liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, hematologic, neurologic, rheumatologic or metabolic disturbances that are uncontrolled with medication change during last three months before Screening and/or that could influence the present general health condition at the Investigator's discretion,
- •Participant has uncontrolled hypertension,
- •Upper respiratory tract and/or chest infection and/or inflammation within 2 weeks preceding the first administration and during the treatment phase,
- •Participant took part in other clinical trial within 90 days preceding the Screening,
- •Known allergy or hypersensitivity, intolerance or contraindication to Esketamine/ketamine or its derivatives and/or to any study product excipients,
- •Blood drawn within 30 days prior to inclusion to the study,
- •History of drug, alcohol, chemical, sedatives or sleeping medications abuse or dependence (except nicotine or caffeine) within 2 years prior to Screening,
- •Lifetime abuse or dependence on ketamine or phencyclidine,
- •Positive results from pregnancy test for female participants,
- •Lactation in female participants,
- •Positive drug screen (except benzodiazepines evaluation during follow-up) or alcohol breath test.
研究组 & 干预措施
Esketamine low dose
Experimental
Participants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).
干预措施: Esketamine DPI - low dose (Drug)
Esketamine medium dose
Experimental
Participants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).
干预措施: Esketamine DPI - medium dose (Drug)
Esketamine high dose
Experimental
Participants are to receive four doses of Esketamine DPI administered over 14-day period (on Day 1, 4, 8 and 11).
干预措施: Esketamine DPI - high dose (Drug)
Placebo
Placebo Comparator
Participants are to receive four doses of Placebo DPI administered over 14-day period (on Day 1, 4, 8 and 11).
干预措施: Placebo DPI (Drug)
结局指标
主要结局
Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at Day 14
时间窗: Day 1 and Day 14
The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The test consists of 10 items, each scored from 0 (symptoms not present or normal) to 6 (severe or continuous presence of the symptoms). Total score is 60. The higher MADRS total score, the more severe depression.
次要结局
- Number of participants with clinical response (>= 50% decrease in MADRS baseline score)(Day 1, 2, 4, 5, 8, 9, 11, 12, 14 and up to 6 weeks after the treatment phase)
- Change from baseline in depression severity, measured by Hamilton Depression Rating Scale (HDRS) at every timepoint(Day 1, 2, 4, 5, 8, 9, 11, 12, 14 and week 3, 4, 5, 6, 7 and 8)
- Number of participants with clinical remission (MADRS total score <= 10)(Day 1, 2, 4, 5, 8, 9, 11, 12, 14 and up to 6 weeks after the treatment phase)
- Esnorketamine AUC0-24h - area under the plasma concentration - time curve from 0 to 24 h(up to 24 hours following the start of first and fourth administration)
- Onset of clinical response that was sustained through the end of the 2-week, double-blind, treatment phase(Day 1, 2, 4, 5, 8, 9, 11, 12, 14)
- Change from baseline in Clinical Global Impression - Severity (CGI-S) score at Day 14 and every other timepoint(Day 1, 2, 4, 5, 8, 9, 11, 12, 14 and week 3, 4, 5, 6, 7 and 8)
- Change from baseline in the Clinician Administered Dissociative States Scale (CADSS) at each day of administration(up to 24 hours following the start of each administration)
- Change from baseline in Columbia Suicide Severity Rating Scale (C-SSRS) at Day 14 and every other timepoint(Day 1, 14 and week 5, 8)
- Esnorketamine Tmax - time to reach maximum concentration in plasma(up to 24 hours following the start of first and fourth administration)
- Esketamine Kel - terminal elimination rate constant(up to 24 hours following the start of first and fourth administration)
- Esketamine t1/2 - plasma elimination half-life(up to 24 hours following the start of first and fourth administration)
- Potential Esketamine effect on cognition as measured by Montreal Cognitive Assessment (MoCA)(Day 0, week 4 and 8)
- Change from baseline in MADRS total score at each other than Day 14 timepoint(Day 1, 2, 4, 5, 8, 9, 11, 12 and week 3, 4, 5, 6, 7 and 8)
- Time to relapse(Day 14 and week 3, 4, 5, 6, 7 and 8)
- Change from baseline in the Brief Psychiatric Rating Scale (BPRS) at each day of administration(up to 24 hours following the start of each administration)
- Severity of manic behaviour as assessed by the Young Mania Rating Scale (YMRS)(Day 0, 3, 7, 10, 14 and week 3, 4, 5, 6, 7, 8)
- Potential withdrawal symptoms after Esketamine treatment, as measured by the 20-item Physician Withdrawal Checklist (PWC-20)(Day 0, week 3, 4 and 5)
- Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(up to 8 weeks)
- Esnorketamine Cmax - maximum plasma concentration(up to 24 hours following the start of first and fourth administration)
- Esketamine AUC0-24h - area under the plasma concentration - time curve from 0 to 24 h(up to 24 hours following the start of first and fourth administration)
- Esketamine Cmax - maximum plasma concentration(up to 24 hours following the start of first and fourth administration)
- Esketamine AUC0-inf - area under the plasma concentration - time curve from 0 to infinity(up to 24 hours following the start of first and fourth administration)
- Esketamine Tmax - time to reach maximum concentration in plasma(up to 24 hours following the start of first and fourth administration)
- Changes between predose and postdose values for each administration in hematology and biochemistry(up to 6 weeks)
- Changes between predose and postdose values for each administration in vital signs (heart rate, blood pressure, respiratory rate) and urinalysis(up to 8 weeks)
- Changes between predose and postdose values for each administration in SpO2 (blood oxygen saturation)(up to 2 hours following the start of each administration)
研究者
研究点 (11)
Loading locations...
相似试验
已完成
2 期
Efficacy, Safety and Pharmacokinetic Study of Inhaled Esketamine in Treatment-resistant DepressionMajor Depressive DisorderNCT03965858Celon Pharma SA88
已完成
3 期
54135419SUI3001: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for SuicideDepressive Disorder, MajorNCT03039192Janssen Research & Development, LLC226
已完成
3 期
54135419SUI3002: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for SuicideDepressive Disorder, MajorNCT03097133Janssen Research & Development, LLC230
已完成
2 期
A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for SuicideMajor Depressive DisorderNCT02133001Janssen Research & Development, LLC68
已完成
2 期
A Study to Evaluate the Safety and Efficacy of Intranasal Esketamine in Treatment-resistant DepressionTreatment Resistant Depressive DisorderNCT01998958Janssen Research & Development, LLC108