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

Recruiting at 46 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Antidepressants

Must not be taking: Ketamine, Esketamine

Disqualifiers: Psychotic disorder, Bipolar, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

99 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called MK-1942 to see if it helps people with depression that doesn't improve with regular treatments. The goal is to find out if MK-1942 can reduce depression symptoms.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable course of antidepressant therapy for at least 4 weeks before joining, so you will not need to stop your current antidepressant medications.

What safety data exists for the treatment known as MK-1942, Placebo, Control, or Dummy Treatment?

In studies involving healthy volunteers, placebo treatments, which are inactive substances, showed that 19% of participants reported side effects like headaches, drowsiness, and weakness. These effects were more common with repeated doses and in older participants. ^{1 2 3 4 5}

How does the drug MK-801 differ from other treatments for memory and learning impairments?

MK-801 is unique because it works by blocking NMDA receptors, which are involved in memory and learning processes. This mechanism can lead to cognitive impairments, making it useful in research to study these effects, unlike other treatments that might aim to improve memory and learning. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

Inclusion Criteria

You are currently going through a period of moderate to severe depression.

You have tried 1 to 4 different antidepressant medications for your current episode of moderate-to-severe depression, but they did not work well enough for you.

Has a reliable contact person

Exclusion Criteria

You have struggled with substance abuse or addiction in the past year or currently.

You have HIV or unstable conditions like hypothyroidism, diabetes, heart problems, or lung problems.

You are allergic to any of the ingredients in the medication MK-1942.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MK-1942 or placebo for 4 weeks, with daily or intermittent dosing

4 weeks

Weekly visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• MK-1942
• Placebo

Participant Groups

Group I: MK-1942 Intermittent Dose Group Experimental Treatment 2 Interventions

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.

Group II: MK-1942 Daily Dose Group Experimental Treatment 2 Interventions

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.

Group III: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

In a study involving 24 rabbits undergoing spine fusion, daily subcutaneous injections of abaloparatide resulted in a 100% fusion rate compared to only 45% in the control group, indicating its strong efficacy in promoting spinal fusion.

Radiographic analysis showed that abaloparatide significantly increased bone formation and quality, with higher bone volume and improved trabecular structure, suggesting it enhances the biological processes necessary for successful spinal fusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abaloparatide Enhances Fusion and Bone Formation in a Rabbit Spinal Arthrodesis Model. Morse, KW., Moore, H., Kumagai, H., et al.[2023]

A new checklist called TIDieR-Placebo has been developed to improve the reporting of placebo or sham interventions in clinical trials, ensuring that researchers clearly describe these components alongside active treatments.

The checklist was created through expert consultation and aims to enhance the transparency of trial results, which is crucial for accurately assessing the benefits and harms of active interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. Howick, J., Webster, RK., Rees, JL., et al.[2020]

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

MK-8389 was found to be generally safe and well tolerated in healthy young women over a 14-day period, although it caused transient changes in thyroid function tests that limited dose escalation above 40 mg.

While MK-8389 showed acceptable systemic exposure, it did not have a clinically meaningful effect on follicular development, although higher doses did increase inhibin B levels, indicating some early follicular activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. Gerrits, MG., Kramer, H., el Galta, R., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Abaloparatide Enhances Fusion and Bone Formation in a Rabbit Spinal Arthrodesis Model. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Short-term effects of dry needling of thenar muscles in manual laborers with carpal tunnel syndrome: a pilot, randomized controlled study. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Effects of dizocilpine (MK-801) on motor activity and memory. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of the N-methyl-d-aspartate receptor antagonist, MK-801, on spatial memory and influence of the route of administration. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Glutamate antagonism during secondary deafferentation enhances cognition and axo-dendritic integrity after traumatic brain injury. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. [2016]