A Phase 2a, Randomized, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of MK-1942 Added to Stable Antidepressant Therapy in Participants With Treatment-Resistant Depression
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 99
- 试验地点
- 88
- 主要终点
- Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 3
研究概览
简要总结
The main purpose of this study is to assess the efficacy and safety of daily and intermittent dosing of MK-1942 compared to placebo among participants with Treatment-Resistant Depression (TRD) on a stable course of antidepressant therapy. The dual primary hypotheses of the study are that the daily MK-1942 treatment or intermittent MK-1942 treatment are superior to placebo in reducing Montgomery-Asberg Depression Rating Scale (MADRS) score.
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)
盲法说明
Double
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
- •Meets the diagnostic criteria for moderate-to-severe major depressive disorder (MDD) without psychotic features according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria at Visit 1 (Screening)
- •Is currently experiencing an episode of moderate-to-severe MDD
- •Had an inadequate response to 1 to 4 different courses of antidepressant therapy for the current episode of moderate-to-severe MDD
- •Has been on a stable course of antidepressant therapy for ≥4 weeks before Visit 1 (Screening)
- •Has not initiated psychotherapy for depressive symptoms in the last 3 months before Visit 1 (Screening) and agrees not to initiate a new psychotherapy for depressive symptoms or to modify their current regimen of psychotherapy for depressive symptoms from Visit 1 (Screening) to Visit 9 (Post-dose Follow-up Visit)
- •Male participants are eligible if they agree to the following during the intervention period and for at least 7 days after last dose of study intervention: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or agrees to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
- •A female participant is eligible to participate if she is not a woman of childbearing potential (WOCBP) or a WOCBP who is not pregnant, breastfeeding, or within 3 months from postpartum. WOCBP should use contraceptive methods that are highly effective as per the study specifications or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, have a negative pregnancy test at screening, immediately prior to the first dosing event, and at regular intervals during the study period, and abstain from breastfeeding during the study intervention period and for at least 7 days after last study intervention
- •Has a reliable contact person
排除标准
- •Has an ongoing episode of MDD that started more than 2 years before Visit 1 (Screening)
- •Has a current or prior history of one or more of the following: a) diagnosis of a psychotic disorder b) chronic convulsive disorder, except febrile seizures during childhood c) neurodegenerative disorder, traumatic brain injury causing ongoing cognitive difficulties, or any chronic organic disease of the central nervous system d) intellectual disability of a severity that would affect the ability of the participant to participate in the study e) bipolar and related disorders, MDD with psychosis f) MDD with mixed features g) posttraumatic stress disorder if not in remission for at least 5 years before Visit 1 (Screening) h) obsessive-compulsive disorder i) autism spectrum disorder
- •Meets criteria for substance abuse or dependence disorder currently or within the 12 months before Visit 1 (Screening)
- •Has a known allergy or intolerance to the active or inert ingredients in MK-1942
- •Has a history of malignancy ≤3 years before Visit 1 (Screening) except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- •Has a Body Mass Index (BMI) >40 kg/m2
- •Has HIV or nonstable hypothyroidism, diabetes, cardiovascular disease, or respiratory disease
- •Failed to adequately respond to treatment with ketamine or esketamine for the current or a prior episode of MDD
- •Previously received electroconvulsive therapy within the past 10 years, deep brain stimulation, or vagal nerve stimulation for treatment of depression
- •Is imminent risk for self harm or harm to others
- •Is currently participating in or has previously participated in an interventional clinical study within the 2 months before Visit 1 (Screening), or has participated in >4 interventional clinical studies within the 2 years before Visit 1 (Screening)
- •Has known renal disease or is experiencing renal insufficiency
- •Routinely consumes >3 alcoholic drinks per day. One standard drink is defined as any beverage containing 14 gram (g) of pure alcohol
- •Requires use of a language interpreter to participate in the study
- •Had major surgery or donated or lost >1 unit of blood within the 4 weeks before Visit 1 (Screening)
- •Is pregnant or is currently breastfeeding or plans to breastfeed during the course of the study
- •Is a woman with <12 months of amenorrhea and is receiving hormone replacement therapy (HRT) or an estrogen-based contraceptive
- •Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study
研究组 & 干预措施
MK-1942 Daily Dose Group
Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
干预措施: MK-1942 (Drug)
MK-1942 Daily Dose Group
Participants receive a total daily dose titrated from 5 mg to 20 mg of MK-1942 twice daily (BID), orally, over 4 weeks of treatment duration: 5 mg in Week 1, 10 mg in Week 2, and 20 mg in Weeks 3 and 4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
干预措施: Placebo (Drug)
MK-1942 Intermittent Dose Group
Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
干预措施: MK-1942 (Drug)
MK-1942 Intermittent Dose Group
Participants receive a total daily dose of 10 mg of MK-1942 twice weekly (BIW), orally, for Weeks 1-4. Participants receive MK-1942 and matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
干预措施: Placebo (Drug)
Placebo
Participants receive a dose-matched placebo BID, orally, for 4 weeks. Participants receive matching placebo packaged in blister cards with an equal number of capsules administered in the morning and evening regardless of treatment assignment.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 3
时间窗: Baseline and Week 3
The change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score is presented. MADRS includes 10 participant-rated items, each scored on a scale from 0 (normal, no symptom) to 6 (symptoms of maximum severity) \[total scores range from 0 (normal/no symptom) to 60 (severe depression). Higher scores correspond to greater symptom severity, whereas a negative change from baseline score indicates improvement.
Change From Baseline in MADRS Total Score to Week 1
时间窗: Baseline and Week 1
The change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score is presented. MADRS includes 10 participant-rated items, each scored on a scale from 0 (normal, no symptom) to 6 (symptoms of maximum severity) \[total scores range from 0 (normal/no symptom) to 60 (severe depression). Higher scores correspond to greater symptom severity, whereas a negative change from baseline score indicates improvement.
Number of Participants Who Experienced An Adverse Event (AE)
时间窗: Up to approximately 6 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to approximately 4 Weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Change From Baseline in the Hamilton Depression Rating Scale (HAM-D17) Total Score to Week 3(Baseline and Week 3)
- Change From Baseline in the HAM-D17 Scale Total Score to Week 1(Baseline and Week 1)
- Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 3(Baseline and Week 3)
- Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 1(Baseline and Week 1)
- Mean Plasma Concentration of MK-1942 Plasma Concentration(Day 15: 12 (Daily Dose) or 72 (Intermittent Dose) hours postdose)