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.
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
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
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.
- Conditions
- Treatment Resistant Depression
- 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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
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
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)
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
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
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
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
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.
- First posted11 Dec 2020
- Study start20 May 2021
- Primary completion8 Sep 2023
- Study completion8 Sep 2023
Why it stopped: Voluntarily terminated due to benefit/risk assessment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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