Efficacy and Safety of MK-1942 When Added to Stable Antidepressant Therapy in Participants With Treatment-Resistant Depression (TRD) (MK-1942-006)
- Registration Number
- NCT04663321
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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 and/or intermittent MK-1942 treatment are superior to placebo in reducing Montgomery-Asberg Depression Rating Scale (MADRS) score.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 99
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MK-1942 Daily Dose Group MK-1942 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. MK-1942 Daily Dose Group Placebo 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. MK-1942 Intermittent Dose Group Placebo 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. Placebo 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. MK-1942 Intermittent Dose Group MK-1942 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 3 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 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) 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 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the Hamilton Depression Rating Scale (HAM-D17) Total Score to Week 3 Baseline and Week 3 The HAM-D17 scale was used to evaluate the depressive symptoms experienced over the past week. The HAM-D17 is a 17-item participant-rated scale, with each item scored from 0 to 2 or 4 (depending on the question) reflective of severity (0 is absence of symptom and higher scores indicate greater symptom severity). The total score ranges from 0 (no apparent symptoms) to 52 (most severe symptoms). A negative change from baseline indicates symptom improvement, and vice versa.
Change From Baseline in the HAM-D17 Scale Total Score to Week 1 Baseline and Week 1 The HAM-D17 scale was used to evaluate the depressive symptoms experienced over the past week. The HAM-D17 is a 17-item participant-rated scale, with each item scored from 0 to 2 or 4 (depending on the question) reflective of severity (0 is absence of symptom and higher scores indicate greater symptom severity). The total score ranges from 0 (no apparent symptoms) to 52 (most severe symptoms). A negative change from baseline indicates symptom improvement, and vice versa.
Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 3 Baseline and Week 3 The CGI-S is rated on a 7-point scale using a range of responses from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher score corresponds to greater symptom severity. A negative change score indicates improvement, and vice versa.
Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 1 Baseline and Week 1 The CGI-S is rated on a 7-point scale using a range of responses from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher score corresponds to greater symptom severity. A negative change score indicates improvement, and vice versa.
Mean Plasma Concentration of MK-1942 Plasma Concentration Day 15: 12 (Daily Dose) or 72 (Intermittent Dose) hours postdose The mean plasma concentration of MK-1942 10 mg given as a single or multiple dose regimen was determined.
Trial Locations
- Locations (45)
Atlanta Center for Medical Research ( Site 1022)
🇺🇸Atlanta, Georgia, United States
Woodland International Research Group ( Site 1017)
🇺🇸Little Rock, Arkansas, United States
Institute of Living ( Site 1061)
🇺🇸Hartford, Connecticut, United States
Preferred Research Partners ( Site 1079)
🇺🇸Little Rock, Arkansas, United States
University of South Florida-Psychiatry and Behavioral Neurosciences ( Site 1093)
🇺🇸Tampa, Florida, United States
Axiom Research ( Site 1053)
🇺🇸Colton, California, United States
CITrials-Outpatient Facility ( Site 1098)
🇺🇸Bellflower, California, United States
APG RESEARCH, LLC ( Site 1087)
🇺🇸Orlando, Florida, United States
K2 Medical Research - Winter Park ( Site 1115)
🇺🇸Winter Park, Florida, United States
University of Michigan-Psychiatry ( Site 1051)
🇺🇸Ann Arbor, Michigan, United States
Psych Atlanta ( Site 1108)
🇺🇸Marietta, Georgia, United States
CBH Health ( Site 1076)
🇺🇸Gaithersburg, Maryland, United States
iResearch Savannah ( Site 1041)
🇺🇸Savannah, Georgia, United States
Hassman Research Institute ( Site 1036)
🇺🇸Berlin, New Jersey, United States
Ascension Saint Elizabeth ( Site 1003)
🇺🇸Chicago, Illinois, United States
Altea Research ( Site 1018)
🇺🇸Las Vegas, Nevada, United States
Manhattan Behavioral Medicine ( Site 1096)
🇺🇸New York, New York, United States
Global Medical Institutes LLC; Princeton Medical Institute ( Site 1049)
🇺🇸Princeton, New Jersey, United States
Neuro-Behavioral Clinical Research ( Site 1045)
🇺🇸North Canton, Ohio, United States
Woodstock Research Center ( Site 1084)
🇺🇸Woodstock, Vermont, United States
Richmond Behavioral Associates ( Site 1011)
🇺🇸Staten Island, New York, United States
Penn Medicine: University of Pennsylvania Health System-Mood Disorders Treatment and Research Proga
🇺🇸Philadelphia, Pennsylvania, United States
Paradigm Research Professionals ( Site 1089)
🇺🇸Oklahoma City, Oklahoma, United States
Baylor College of Medicine ( Site 1019)
🇺🇸Houston, Texas, United States
AIM Trials, LLC ( Site 1111)
🇺🇸Plano, Texas, United States
Northwest Clinical Research Center ( Site 1112)
🇺🇸Bellevue, Washington, United States
University of Alabama at Birmingham - School of Medicine-Psychiatry ( Site 1073)
🇺🇸Birmingham, Alabama, United States
CITrials ( Site 1105)
🇺🇸Santa Ana, California, United States
Collaborative Neuroscience Network, LLC. ( Site 1032)
🇺🇸Garden Grove, California, United States
Gulfcoast Clinical Research Center ( Site 1110)
🇺🇸Fort Myers, Florida, United States
Aqualane Clinical Research ( Site 1113)
🇺🇸Naples, Florida, United States
Behavioral Clinical Research ( Site 1037)
🇺🇸Miami, Florida, United States
iResearch Atlanta ( Site 1040)
🇺🇸Decatur, Georgia, United States
Boston Clinical Trials ( Site 1028)
🇺🇸Boston, Massachusetts, United States
New Hope Clinical Research ( Site 1082)
🇺🇸Charlotte, North Carolina, United States
Clinical Trials of America, LLC ( Site 1103)
🇺🇸Hickory, North Carolina, United States
Hapworth Research Inc.-Clinical Research Department ( Site 1090)
🇺🇸New York, New York, United States
Velocity Clinical Research, Hallandale Beach ( Site 1116)
🇺🇸Hallandale Beach, Florida, United States
Cedar Clinical Research ( Site 1023)
🇺🇸Draper, Utah, United States
Suburban Research Associates-Clinical Research ( Site 1042)
🇺🇸Media, Pennsylvania, United States
Keystone Clinical Studies ( Site 1031)
🇺🇸Plymouth Meeting, Pennsylvania, United States
Clinical Neuroscience Solutions, Inc. dba CNS Healthcare ( Site 1039)
🇺🇸Jacksonville, Florida, United States
Albuquerque Neuroscience Inc. ( Site 1107)
🇺🇸Albuquerque, New Mexico, United States
Core Clinical Research ( Site 1081)
🇺🇸Everett, Washington, United States
Innovative Clinical Research ( Site 1044)
🇺🇸Lauderhill, Florida, United States