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Treatment Resistant DepressionPhase 2NCT04663321

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

A Phase 2 study testing MK-1942 in people with Treatment Resistant Depression, run by Merck Sharp & Dohme LLC at 45 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Treatment Resistant Depression
What is being tested?
MK-1942
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
99 participants
Where
45 sitesUnited States
Study dates
20 May 2021to 8 Sep 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

45 sites in 1 country.

45 sites in 1 country

United States45 sites

  • Albuquerque Neuroscience Inc. ( Site 1107)

    Albuquerque, New Mexico, 87109

  • University of Michigan-Psychiatry ( Site 1051)

    Ann Arbor, Michigan, 48026

  • Atlanta Center for Medical Research ( Site 1022)

    Atlanta, Georgia, 30331

  • Northwest Clinical Research Center ( Site 1112)

    Bellevue, Washington, 98007

  • CITrials-Outpatient Facility ( Site 1098)

    Bellflower, California, 90706

  • Hassman Research Institute ( Site 1036)

    Berlin, New Jersey, 08009

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

    Birmingham, Alabama, 35233

  • Boston Clinical Trials ( Site 1028)

    Boston, Massachusetts, 02131

  • New Hope Clinical Research ( Site 1082)

    Charlotte, North Carolina, 28211

  • Ascension Saint Elizabeth ( Site 1003)

    Chicago, Illinois, 60622

  • Axiom Research ( Site 1053)

    Colton, California, 92324

  • iResearch Atlanta ( Site 1040)

    Decatur, Georgia, 30030

  • Cedar Clinical Research ( Site 1023)

    Draper, Utah, 84020

  • Core Clinical Research ( Site 1081)

    Everett, Washington, 98201

  • Gulfcoast Clinical Research Center ( Site 1110)

    Fort Myers, Florida, 33912

  • CBH Health ( Site 1076)

    Gaithersburg, Maryland, 20877

  • Collaborative Neuroscience Network, LLC. ( Site 1032)

    Garden Grove, California, 92845

  • Velocity Clinical Research, Hallandale Beach ( Site 1116)

    Hallandale, Florida, 33009

  • Institute of Living ( Site 1061)

    Hartford, Connecticut, 06106

  • Clinical Trials of America, LLC ( Site 1103)

    Hickory, North Carolina, 28601

  • Baylor College of Medicine ( Site 1019)

    Houston, Texas, 77030

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

    Jacksonville, Florida, 32256

  • Altea Research ( Site 1018)

    Las Vegas, Nevada, 89102

  • Innovative Clinical Research ( Site 1044)

    Lauderhill, Florida, 33319

  • Preferred Research Partners ( Site 1079)

    Little Rock, Arkansas, 72211

  • Woodland International Research Group ( Site 1017)

    Little Rock, Arkansas, 72211

  • Psych Atlanta ( Site 1108)

    Marietta, Georgia, 30060

  • Suburban Research Associates-Clinical Research ( Site 1042)

    Media, Pennsylvania, 19063

  • Behavioral Clinical Research ( Site 1037)

    Miami, Florida, 33016

  • Aqualane Clinical Research ( Site 1113)

    Naples, Florida, 34105

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

    New York, New York, 10022

  • Manhattan Behavioral Medicine ( Site 1096)

    New York, New York, 10036

  • Neuro-Behavioral Clinical Research ( Site 1045)

    North Canton, Ohio, 44720

  • Paradigm Research Professionals ( Site 1089)

    Oklahoma City, Oklahoma, 73118

  • APG RESEARCH, LLC ( Site 1087)

    Orlando, Florida, 32803

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

    Philadelphia, Pennsylvania, 19104

  • AIM Trials, LLC ( Site 1111)

    Plano, Texas, 75093

  • Keystone Clinical Studies ( Site 1031)

    Plymouth Meeting, Pennsylvania, 19462

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

    Princeton, New Jersey, 08540

  • CITrials ( Site 1105)

    Santa Ana, California, 92705

  • iResearch Savannah ( Site 1041)

    Savannah, Georgia, 31405

  • Richmond Behavioral Associates ( Site 1011)

    Staten Island, New York, 10314

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

    Tampa, Florida, 33613

  • K2 Medical Research - Winter Park ( Site 1115)

    Winter Park, Florida, 32792

  • Woodstock Research Center ( Site 1084)

    Woodstock, Vermont, 05091

Other trials in United States

About this study

Official title: 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.

Being tested
MK-1942, Placebo
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-1942Drug

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

  • PlaceboDrug

    Dose matched placebo capsules BID orally over 4 weeks.

Study groups in NCT04663321
Study groupRoleWhat they receive
MK-1942 Daily Dose GroupExperimentalParticipants 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.
Receives: Drug: MK-1942; Drug: Placebo
MK-1942 Intermittent Dose GroupExperimentalParticipants 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.
Receives: Drug: MK-1942; Drug: Placebo
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and Week 3

  2. 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.

    Measured: Baseline and Week 1

  3. 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.

    Measured: Up to approximately 6 Weeks

  4. 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.

    Measured: Up to approximately 4 Weeks

Secondary outcomes (5)

  1. 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.

    Measured: Baseline and Week 3

  2. 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.

    Measured: Baseline and Week 1

  3. 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.

    Measured: Baseline and Week 3

  4. 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.

    Measured: Baseline and Week 1

  5. 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.

    Measured: Day 15: 12 (Daily Dose) or 72 (Intermittent Dose) hours postdose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2020
  2. Study start20 May 2021
  3. Primary completion8 Sep 2023
  4. Study completion8 Sep 2023

Why it stopped: Voluntarily terminated due to benefit/risk assessment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
99 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04663321
Sponsor's protocol ID
1942-006
Other IDs
MK-1942-006
Status last verified
Apr 2026
First submitted
4 Dec 2020
Last updated
4 May 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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 Jul-Aug 01;46(4):427-432. doi: 10.1097/JCP.0000000000002171. Epub 2026 Mar 19.

    PubMed 41854661

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MK-1942 in people with Treatment Resistant Depression, run by Merck Sharp & Dohme LLC at 45 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 3 (time frame: Baseline and Week 3). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04663321, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.

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