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

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.


Eligibility Criteria:
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