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

Treatment Resistant Depression Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04663321
• Other study ID #: 1942-006
• Secondary ID: MK-1942-006
• Status: Terminated
• Phase: Phase 2
• Start date: May 20, 2021
• Est. completion date: September 8, 2023

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. The dual primary hypotheses of the study are that the daily MK-1942 treatment and/or intermittent MK-1942 treatment are superior to placebo in reducing Montgomery-Asberg Depression Rating Scale (MADRS) score.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 99
• Est. completion date: September 8, 2023
• Est. primary completion date: September 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

Drug:
• MK-1942
MK-1942 (5 mg or 10 mg capsules) titrated from 5 mg to 20 mg dose BID or 10 mg BIW over 4 weeks.
• Placebo
Dose matched placebo capsules BID orally over 4 weeks.

Locations

Country	Name	City	State
United States	Albuquerque Neuroscience Inc. ( Site 1107)	Albuquerque	New Mexico
United States	University of Michigan-Psychiatry ( Site 1051)	Ann Arbor	Michigan
United States	Atlanta Center for Medical Research ( Site 1022)	Atlanta	Georgia
United States	Northwest Clinical Research Center ( Site 1112)	Bellevue	Washington
United States	CITrials-Outpatient Facility ( Site 1098)	Bellflower	California
United States	Hassman Research Institute ( Site 1036)	Berlin	New Jersey
United States	University of Alabama at Birmingham - School of Medicine-Psychiatry ( Site 1073)	Birmingham	Alabama
United States	Boston Clinical Trials ( Site 1028)	Boston	Massachusetts
United States	New Hope Clinical Research ( Site 1082)	Charlotte	North Carolina
United States	Ascension Saint Elizabeth ( Site 1003)	Chicago	Illinois
United States	Axiom Research ( Site 1053)	Colton	California
United States	iResearch Atlanta ( Site 1040)	Decatur	Georgia
United States	Cedar Clinical Research ( Site 1023)	Draper	Utah
United States	Core Clinical Research ( Site 1081)	Everett	Washington
United States	Gulfcoast Clinical Research Center ( Site 1110)	Fort Myers	Florida
United States	CBH Health ( Site 1076)	Gaithersburg	Maryland
United States	Collaborative Neuroscience Network, LLC. ( Site 1032)	Garden Grove	California
United States	Velocity Clinical Research, Hallandale Beach ( Site 1116)	Hallandale Beach	Florida
United States	Institute of Living ( Site 1061)	Hartford	Connecticut
United States	Clinical Trials of America, LLC ( Site 1103)	Hickory	North Carolina
United States	Baylor College of Medicine ( Site 1019)	Houston	Texas
United States	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare ( Site 1039)	Jacksonville	Florida
United States	Altea Research ( Site 1018)	Las Vegas	Nevada
United States	Innovative Clinical Research ( Site 1044)	Lauderhill	Florida
United States	Preferred Research Partners ( Site 1079)	Little Rock	Arkansas
United States	Woodland International Research Group ( Site 1017)	Little Rock	Arkansas
United States	Psych Atlanta ( Site 1108)	Marietta	Georgia
United States	Suburban Research Associates-Clinical Research ( Site 1042)	Media	Pennsylvania
United States	Behavioral Clinical Research ( Site 1037)	Miami	Florida
United States	Aqualane Clinical Research ( Site 1113)	Naples	Florida
United States	Hapworth Research Inc.-Clinical Research Department ( Site 1090)	New York	New York
United States	Manhattan Behavioral Medicine ( Site 1096)	New York	New York
United States	Neuro-Behavioral Clinical Research ( Site 1045)	North Canton	Ohio
United States	Paradigm Research Professionals ( Site 1089)	Oklahoma City	Oklahoma
United States	APG RESEARCH, LLC ( Site 1087)	Orlando	Florida
United States	Penn Medicine: University of Pennsylvania Health System-Mood Disorders Treatment and Research Proga	Philadelphia	Pennsylvania
United States	AIM Trials, LLC ( Site 1111)	Plano	Texas
United States	Keystone Clinical Studies ( Site 1031)	Plymouth Meeting	Pennsylvania
United States	Global Medical Institutes LLC; Princeton Medical Institute ( Site 1049)	Princeton	New Jersey
United States	CITrials ( Site 1105)	Santa Ana	California
United States	iResearch Savannah ( Site 1041)	Savannah	Georgia
United States	Richmond Behavioral Associates ( Site 1011)	Staten Island	New York
United States	University of South Florida-Psychiatry and Behavioral Neurosciences ( Site 1093)	Tampa	Florida
United States	K2 Medical Research - Winter Park ( Site 1115)	Winter Park	Florida
United States	Woodstock Research Center ( Site 1084)	Woodstock	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 3	The 10-item MADRS scale will be used to evaluate the severity of depressive symptoms. Participants receiving daily dose of MK-1942 will be rated on 10 items, rated on a scale from 0 (normal, no symptom) to 6 (symptoms of maximum severity) with total scores ranging from 0 (normal/no symptom) to 60 (severe depression). Higher scores correspond to greater symptom severity. A negative change score indicates improvement. The longitudinal analysis of covariance (ANCOVA) model will be used to report the mean change from baseline in the MADRS total score to Week 3.	Baseline, Week 3
Primary	Change From Baseline in MADRS Total Score to Week 1	The 10-item MADRS scale will be used to evaluate the severity of depressive symptoms. Participants receiving intermittent dose of MK-1942 will be rated on 10 items, rated on a scale from 0 (normal, no symptom) to 6 (symptoms of maximum severity) with total scores ranging from 0 (normal/no symptom) to 60 (severe depression). Higher scores correspond to greater symptom severity. A negative change score indicates improvement. The longitudinal analysis of covariance (ANCOVA) model will be used to report the mean change from baseline in the MADRS total score to Week 1.	Baseline, Week 1
Primary	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.	Up to approximately 6 Weeks
Primary	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.	Up to approximately 4 Weeks
Secondary	Change From Baseline in the Hamilton Depression Rating Scale (HAM-D17) Total Score to Week 3	The 17 item HAM-D17 scale will be used to evaluate the depressive symptoms experienced over the past week among participants who received daily dose of MK-1942. Participants will be rated using 17 individual items. Each item is rated on a scale from 0 to 2 or 0 to 4 reflective of severity (0 being absence of symptom and higher scores being more severe), with total scores ranging from 0 (no apparent symptoms) to 52 (most severe symptoms). Higher scores correspond to greater symptom. A negative change score indicates improvement. The longitudinal ANCOVA model will be used to report the mean change from baseline in HAM-D17 total score to Week 3.	Baseline, Week 3
Secondary	Change From Baseline in the HAM-D17 Scale Total Score to Week 1	The 17 item HAM-D17 scale will be used to evaluate the depressive symptoms experienced over the past week among participants who received intermittent dose of MK-1942. Participants will be rated using 17 individual items. Each item is rated on a scale from 0 to 2 or 0 to 4 reflective of severity (0 being absence of symptom and higher scores being more severe), with total scores ranging from 0 (no apparent symptoms) to 52 (most severe symptoms). Higher scores correspond to greater symptom severity. A negative change score indicates improvement. The longitudinal ANCOVA model will be used to report the mean change from baseline in HAM-D17 total score to Week 1.	Baseline, Week 1
Secondary	Change From Baseline in the Clinician Global Impression-Severity (CGI-S) Total Score to Week 3	A single-item CGI-S scale will be used to assess the severity of depression among participants who received daily dose of MK-1942. 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. The longitudinal ANCOVA model will be used to report the mean change from baseline in CGI-S score to Week 3.	Baseline, Week 3
Secondary	Change From Baseline in the CGI-S Total Score to Week 1	A single-item CGI-S scale will be used to assess the severity of depression among participants who received intermittent dose of MK-1942. 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. The longitudinal ANCOVA model will be used to report the mean change from baseline in CGI-S score to Week 1.	Baseline, Week 1
Secondary	Mean Plasma Concentration of MK-1942 plasma concentration	Blood samples will be collected at predetermined predose and postdose specified timepoints to report the mean plasma concentration of MK-1942 at prespecified timepoints.	Week 0 (Day 1): Predose and 1-hour postdose and Weeks 1, 2, 3 & 4: Predose

External Links

•   Merck Clinical Trials Information