Clinical trial NCT04663321: Efficacy and Safety of MK-1942 When Added to Stable Antidepressant Therapy in Participants With Treatment-Resistant Depression (TRD) (MK-1942-006)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Treatment Resistant Depression
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-12-11
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 3
timeFrame: Baseline and Week 3
measure: Change From Baseline in MADRS Total Score to Week 1
timeFrame: Baseline and Week 1
measure: Number of Participants Who Experienced An Adverse Event (AE)
timeFrame: Up to approximately 6 Weeks
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 4 Weeks
Secondary outcomes:
measure: Change From Baseline in the Hamilton Depression Rating Scale (HAM-D17) Total Score to Week 3
timeFrame: Baseline and Week 3
measure: Change From Baseline in the HAM-D17 Scale Total Score to Week 1
timeFrame: Baseline and Week 1
measure: Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 3
timeFrame: Baseline and Week 3
measure: Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 1
timeFrame: Baseline and Week 1
measure: Mean Plasma Concentration of MK-1942 Plasma Concentration
timeFrame: Day 15: 12 (Daily Dose) or 72 (Intermittent Dose) hours postdose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - School of Medicine-Psychiatry ( Site 1073)
state: Alabama
city: Little Rock
country: United States
facility: Preferred Research Partners ( Site 1079)
state: Arkansas
city: Little Rock
country: United States
facility: Woodland International Research Group ( Site 1017)
state: Arkansas
city: Bellflower
country: United States
facility: CITrials-Outpatient Facility ( Site 1098)
state: California
city: Colton
country: United States
facility: Axiom Research ( Site 1053)
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Network, LLC. ( Site 1032)
state: California
city: Santa Ana
country: United States
facility: CITrials ( Site 1105)
state: California
city: Hartford
country: United States
facility: Institute of Living ( Site 1061)
state: Connecticut
city: Fort Myers
country: United States
facility: Gulfcoast Clinical Research Center ( Site 1110)
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach ( Site 1116)
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc. dba CNS Healthcare ( Site 1039)
state: Florida
city: Lauderhill
country: United States
facility: Innovative Clinical Research ( Site 1044)
state: Florida
city: Miami
country: United States
facility: Behavioral Clinical Research ( Site 1037)
state: Florida
city: Naples
country: United States
facility: Aqualane Clinical Research ( Site 1113)
state: Florida
city: Orlando
country: United States
facility: APG RESEARCH, LLC ( Site 1087)
state: Florida
city: Tampa
country: United States
facility: University of South Florida-Psychiatry and Behavioral Neurosciences ( Site 1093)
state: Florida
city: Winter Park
country: United States
facility: K2 Medical Research - Winter Park ( Site 1115)
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research ( Site 1022)
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta ( Site 1040)
state: Georgia
city: Marietta
country: United States
facility: Psych Atlanta ( Site 1108)
state: Georgia
city: Savannah
country: United States
facility: iResearch Savannah ( Site 1041)
state: Georgia
city: Chicago
country: United States
facility: Ascension Saint Elizabeth ( Site 1003)
state: Illinois
city: Gaithersburg
country: United States
facility: CBH Health ( Site 1076)
state: Maryland
city: Boston
country: United States
facility: Boston Clinical Trials ( Site 1028)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan-Psychiatry ( Site 1051)
state: Michigan
city: Las Vegas
country: United States
facility: Altea Research ( Site 1018)
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute ( Site 1036)
state: New Jersey
city: Princeton
country: United States
facility: Global Medical Institutes LLC; Princeton Medical Institute ( Site 1049)
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience Inc. ( Site 1107)
state: New Mexico
city: New York
country: United States
facility: Hapworth Research Inc.-Clinical Research Department ( Site 1090)
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine ( Site 1096)
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates ( Site 1011)
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research ( Site 1082)
state: North Carolina
city: Hickory
country: United States
facility: Clinical Trials of America, LLC ( Site 1103)
state: North Carolina
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research ( Site 1045)
state: Ohio
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals ( Site 1089)
state: Oklahoma
city: Media
country: United States
facility: Suburban Research Associates-Clinical Research ( Site 1042)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System-Mood Disorders Treatment and Research Proga
state: Pennsylvania
city: Plymouth Meeting
country: United States
facility: Keystone Clinical Studies ( Site 1031)
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine ( Site 1019)
state: Texas
city: Plano
country: United States
facility: AIM Trials, LLC ( Site 1111)
state: Texas
city: Draper
country: United States
facility: Cedar Clinical Research ( Site 1023)
state: Utah
city: Woodstock
country: United States
facility: Woodstock Research Center ( Site 1084)
state: Vermont
city: Bellevue
country: United States
facility: Northwest Clinical Research Center ( Site 1112)
state: Washington
city: Everett
country: United States
facility: Core Clinical Research ( Site 1081)
state: Washington
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: