Efficacy and Safety of MK-1942 When Added to Stable Antidepressant Therapy in Participants With Treatment-Resistant Depression (TRD) (MK-1942-006)

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

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.

Study Overview

• Status: Terminated
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Drug: MK-1942; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham - School of Medicine-Psychiatry ( Site 1073)
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners ( Site 1079)
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group ( Site 1017)
  • California
    • Bellflower, California, United States, 90706
      • CITrials-Outpatient Facility ( Site 1098)
    • Colton, California, United States, 92324
      • Axiom Research ( Site 1053)
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Network, LLC. ( Site 1032)
    • Santa Ana, California, United States, 92705
      • CITrials ( Site 1105)
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Institute of Living ( Site 1061)
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center ( Site 1110)
    • Hallandale, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 1116)
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare ( Site 1039)
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research ( Site 1044)
    • Miami, Florida, United States, 33016
      • Behavioral Clinical Research ( Site 1037)
    • Naples, Florida, United States, 34105
      • Aqualane Clinical Research ( Site 1113)
    • Orlando, Florida, United States, 32803
      • APG RESEARCH, LLC ( Site 1087)
    • Tampa, Florida, United States, 33613
      • University of South Florida-Psychiatry and Behavioral Neurosciences ( Site 1093)
    • Winter Park, Florida, United States, 32792
      • K2 Medical Research - Winter Park ( Site 1115)
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research ( Site 1022)
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta ( Site 1040)
    • Marietta, Georgia, United States, 30060
      • Psych Atlanta ( Site 1108)
    • Savannah, Georgia, United States, 31405
      • iResearch Savannah ( Site 1041)
  • Illinois
    • Chicago, Illinois, United States, 60622
      • Ascension Saint Elizabeth ( Site 1003)
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health ( Site 1076)
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials ( Site 1028)
  • Michigan
    • Ann Arbor, Michigan, United States, 48026
      • University of Michigan-Psychiatry ( Site 1051)
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research ( Site 1018)
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute ( Site 1036)
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes LLC; Princeton Medical Institute ( Site 1049)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience Inc. ( Site 1107)
  • New York
    • New York, New York, United States, 10022
      • Hapworth Research Inc.-Clinical Research Department ( Site 1090)
    • New York, New York, United States, 10036
      • Manhattan Behavioral Medicine ( Site 1096)
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates ( Site 1011)
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research ( Site 1082)
    • Hickory, North Carolina, United States, 28601
      • Clinical Trials of America, LLC ( Site 1103)
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research ( Site 1045)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
      • Paradigm Research Professionals ( Site 1089)
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates-Clinical Research ( Site 1042)
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine: University of Pennsylvania Health System-Mood Disorders Treatment and Research Proga
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Keystone Clinical Studies ( Site 1031)
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine ( Site 1019)
    • Plano, Texas, United States, 75093
      • AIM Trials, LLC ( Site 1111)
  • Utah
    • Draper, Utah, United States, 84020
      • Cedar Clinical Research ( Site 1023)
  • Vermont
    • Woodstock, Vermont, United States, 05091
      • Woodstock Research Center ( Site 1084)
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center ( Site 1112)
    • Everett, Washington, United States, 98201
      • Core Clinical Research ( Site 1081)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: MK-1942; MK-1942 (5 mg or 10 mg capsules) titrated from 5 mg to 20 mg dose BID or 10 mg BIW over 4 weeks.; Drug: Placebo; Dose matched placebo capsules BID orally over 4 weeks.
Experimental: 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.	Drug: MK-1942; MK-1942 (5 mg or 10 mg capsules) titrated from 5 mg to 20 mg dose BID or 10 mg BIW over 4 weeks.; Drug: Placebo; Dose matched placebo capsules BID orally over 4 weeks.
Placebo Comparator: 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.	Drug: Placebo; Dose matched placebo capsules BID orally over 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced An Adverse Event (AE)	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.	Up to approximately 6 Weeks
Number of Participants Who Discontinued Study Treatment Due to an AE	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.	Up to approximately 4 Weeks
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to 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.	Baseline and Week 3
Change From Baseline in MADRS Total Score to 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.	Baseline and Week 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Hamilton Depression Rating Scale (HAM-D17) Total Score to 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.	Baseline and Week 3
Change From Baseline in the HAM-D17 Scale Total Score to 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.	Baseline and Week 1
Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to 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.	Baseline and Week 3
Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to 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.	Baseline and Week 1
Mean Plasma Concentration of MK-1942 Plasma Concentration	The mean plasma concentration of MK-1942 10 mg given as a single or multiple dose regimen was determined.	Day 15: 12 (Daily Dose) or 72 (Intermittent Dose) hours postdose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Merola A, Mukai Y, Bueters T, Ceesay P, Dupre N, Furtek C, Sanacora G, Thase ME, Targum SD, Smith SM, Egan MF. Phase 2 Clinical Trial of MK-1942, a Negative Allosteric Modulator of Metabotropic Glutamate Receptor 2, for Treatment-Resistant Depression. J Clin Psychopharmacol. 2026 Mar 19. doi: 10.1097/JCP.0000000000002171. Online ahead of print.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Actual): September 8, 2023
• Study Completion (Actual): September 8, 2023

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 4, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 1942-006; MK-1942-006 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No