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

NCT04663321 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 1942-006MK-1942-006
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 45

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 or intermittent MK-1942 treatment are superior to placebo in reducing Montgomery-Asberg Depression Rating Scale (MADRS) score.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (4)

• 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

• 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

Secondary Outcomes (5)

• 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

Study Arms (3)

MK-1942 Daily Dose Group

EXPERIMENTAL

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; Drug: Placebo

MK-1942 Intermittent Dose Group

EXPERIMENTAL

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; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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

Interventions

MK-1942 DRUG

MK-1942 (5 mg or 10 mg capsules) titrated from 5 mg to 20 mg dose BID or 10 mg BIW over 4 weeks.

MK-1942 Daily Dose Group; MK-1942 Intermittent Dose Group

Placebo DRUG

Dose matched placebo capsules BID orally over 4 weeks.

MK-1942 Daily Dose Group; MK-1942 Intermittent Dose Group; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (45)

University of Alabama at Birmingham - School of Medicine-Psychiatry ( Site 1073)

Birmingham, Alabama, 35233, United States

Location

Preferred Research Partners ( Site 1079)

Little Rock, Arkansas, 72211, United States

Location

Woodland International Research Group ( Site 1017)

Little Rock, Arkansas, 72211, United States

Location

CITrials-Outpatient Facility ( Site 1098)

Bellflower, California, 90706, United States

Location

Axiom Research ( Site 1053)

Colton, California, 92324, United States

Location

Collaborative Neuroscience Network, LLC. ( Site 1032)

Garden Grove, California, 92845, United States

Location

CITrials ( Site 1105)

Santa Ana, California, 92705, United States

Location

Institute of Living ( Site 1061)

Hartford, Connecticut, 06106, United States

Location

Gulfcoast Clinical Research Center ( Site 1110)

Fort Myers, Florida, 33912, United States

Location

Velocity Clinical Research, Hallandale Beach ( Site 1116)

Hallandale, Florida, 33009, United States

Location

Clinical Neuroscience Solutions, Inc. dba CNS Healthcare ( Site 1039)

Jacksonville, Florida, 32256, United States

Location

Innovative Clinical Research ( Site 1044)

Lauderhill, Florida, 33319, United States

Location

Behavioral Clinical Research ( Site 1037)

Miami, Florida, 33016, United States

Location

Aqualane Clinical Research ( Site 1113)

Naples, Florida, 34105, United States

Location

APG RESEARCH, LLC ( Site 1087)

Orlando, Florida, 32803, United States

Location

University of South Florida-Psychiatry and Behavioral Neurosciences ( Site 1093)

Tampa, Florida, 33613, United States

Location

K2 Medical Research - Winter Park ( Site 1115)

Winter Park, Florida, 32792, United States

Location

Atlanta Center for Medical Research ( Site 1022)

Atlanta, Georgia, 30331, United States

Location

iResearch Atlanta ( Site 1040)

Decatur, Georgia, 30030, United States

Location

Psych Atlanta ( Site 1108)

Marietta, Georgia, 30060, United States

Location

iResearch Savannah ( Site 1041)

Savannah, Georgia, 31405, United States

Location

Ascension Saint Elizabeth ( Site 1003)

Chicago, Illinois, 60622, United States

Location

CBH Health ( Site 1076)

Gaithersburg, Maryland, 20877, United States

Location

Boston Clinical Trials ( Site 1028)

Boston, Massachusetts, 02131, United States

Location

University of Michigan-Psychiatry ( Site 1051)

Ann Arbor, Michigan, 48026, United States

Location

Altea Research ( Site 1018)

Las Vegas, Nevada, 89102, United States

Location

Hassman Research Institute ( Site 1036)

Berlin, New Jersey, 08009, United States

Location

Global Medical Institutes LLC; Princeton Medical Institute ( Site 1049)

Princeton, New Jersey, 08540, United States

Location

Albuquerque Neuroscience Inc. ( Site 1107)

Albuquerque, New Mexico, 87109, United States

Location

Hapworth Research Inc.-Clinical Research Department ( Site 1090)

New York, New York, 10022, United States

Location

Manhattan Behavioral Medicine ( Site 1096)

New York, New York, 10036, United States

Location

Richmond Behavioral Associates ( Site 1011)

Staten Island, New York, 10314, United States

Location

New Hope Clinical Research ( Site 1082)

Charlotte, North Carolina, 28211, United States

Location

Clinical Trials of America, LLC ( Site 1103)

Hickory, North Carolina, 28601, United States

Location

Neuro-Behavioral Clinical Research ( Site 1045)

North Canton, Ohio, 44720, United States

Location

Paradigm Research Professionals ( Site 1089)

Oklahoma City, Oklahoma, 73118, United States

Location

Suburban Research Associates-Clinical Research ( Site 1042)

Media, Pennsylvania, 19063, United States

Location

Penn Medicine: University of Pennsylvania Health System-Mood Disorders Treatment and Research Proga

Philadelphia, Pennsylvania, 19104, United States

Location

Keystone Clinical Studies ( Site 1031)

Plymouth Meeting, Pennsylvania, 19462, United States

Location

Baylor College of Medicine ( Site 1019)

Houston, Texas, 77030, United States

Location

AIM Trials, LLC ( Site 1111)

Plano, Texas, 75093, United States

Location

Cedar Clinical Research ( Site 1023)

Draper, Utah, 84020, United States

Location

Woodstock Research Center ( Site 1084)

Woodstock, Vermont, 05091, United States

Location

Northwest Clinical Research Center ( Site 1112)

Bellevue, Washington, 98007, United States

Location

Core Clinical Research ( Site 1081)

Everett, Washington, 98201, United States

Location

Related Publications (1)

• 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.

  PMID: 41854661 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: December 11, 2020
• Study Start: May 20, 2021
• Primary Completion: September 8, 2023
• Study Completion: September 8, 2023
• Last Updated: May 4, 2026
• Results First Posted: September 19, 2024

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (45)