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

Inclusion Criteria

• Males and females (of non-childbearing potential) 18-65 with moderate-to-sever MDD without psychotic features
• BMI <38 kg/m2
• Had an inadequate response to 2-4 different courses of ADT therapy of sufficient dose and duration (MGH-ATRQ) in the current episode
• Inadequate response is defined as ≤25% improvement in depressive symptoms following ADT therapy
• Tachyphylaxis is not a failure
• Increase in dose is still only 1 failure
• On a stable course of ADT therapy for ≥4 weeks before screening
• Prescribed doses and regimens of prior medications should be stable for ≥3 months before screening
• Has a reliable contact person (family member, social worker, case worker, case manager, or nurse) identified for emergent situations

Exclusion Criteria

• Depressive episode >2 years before screening
• Initiation of psychotherapy for depressive symptoms in the last 3 months before screening\
• Current or prior diagnosis of a psychotic disorder, bipolar and related disorders, MDD with psychosis, MDD with mixed features, posttraumatic stress disorder, obsessive-compulsive disorder, or autism spectrum disorder
• Chronic convulsion disorder (epilepsy or seizure disorder), except febrile seizures during childhood
• Neurodegenerative disorder (Parkingson’s, Alzheimer’s, Huntington’s), TBI causing ongoing cognitive difficulties, or any chronic organic disease of the CNS
• Intellectual disability of a severity that would affect the ability to participate
• Is or was under involuntary commitment for the current episode of MDD, because the participant is a danger to themselves or others
• Substance abuse disorder currently or within 12 months of screening
• Routinely consumes >3 alcoholic drinks per day or a positive breath test for alcohol at screening
• History of malignancy ≤3 years prior to screening
• Has HIV, nonstable hypothyroidism, diabetes, cardiovascular disease, respiratory disease, or another chronic medical condition that is not considered to be adequately treated
• Is at imminent risk of self-harm, suicidal ideation with intent, with or without a plan or methods in the past 2 months or suicidal behavior in the past 6 months
• Previously received ECT, TMS, DBS, or VNS for treatment of depression
• Failed to adequately respond to treatment with ketamine or esketamine for the current or a prior episode of MDD
• Has participated in a clinical study within 2 months of screening or has participated in >5 within the last 2 years