MK-8527 + FTC/TDF for Healthy Subjects

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Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Low bone density, Renal impairment, Autoimmune disorders, Cancer, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this study is to learn what happens to MK-8527 in a healthy person's body over time, called a pharmacokinetic (PK) study. Researchers want to learn if there is a difference in the healthy person's body when MK-8527 is taken as a single dose (Treatment A) or with the medication Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) (Treatment B).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What makes the drug MK-8527 + FTC/TDF unique compared to other treatments?

The drug MK-8527 combined with FTC/TDF is unique because it involves a novel compound, MK-8527, which is not widely studied or used in standard treatments. This combination may offer a new approach to treatment, potentially with different mechanisms or effects compared to existing therapies. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This clinical trial is open to healthy adults who haven't smoked or used nicotine/tobacco products for at least 3 months and have a BMI between ≥18 and ≤32.0 kg/m2.

Inclusion Criteria

Has body mass index (BMI) ≥18 and ≤32.0 kg/m^2

I haven't smoked or used nicotine products for at least 3 months.

Exclusion Criteria

Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)

I have a history of conditions like low bone density, kidney issues, or autoimmune disorders.

I have had cancer before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment A

Participants receive a single dose of MK-8527

1 day

1 visit (in-person)

Treatment B

Participants receive FTC/TDF then MK-8527

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• MK-8527 (Other)

Trial Overview The study is examining how MK-8527 behaves in the body over time alone (Treatment A) versus when taken with FTC/TDF (Treatment B), which are medications used in combination therapy.

Participant Groups

Group I: Treatment B: MK-8527 + FTC/TDF Experimental Treatment 2 Interventions

Participants receive FTC/TDF then MK-8527.

Group II: Treatment A: MK-8527 Experimental Treatment 1 Intervention

Participants receive a single dose of MK-8527.

Who Is Running the Clinical Trial?

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 confirmed that [(18)F]FTC-146 specifically binds to sigma-1 receptors (S1Rs) with negligible affinity for the vesicular acetylcholine transporter, indicating its potential as a targeted radiotracer for imaging S1R-related diseases.

Toxicity studies showed no significant adverse effects even at doses 250 times higher than the expected clinical dose, supporting the safety of [(18)F]FTC-146 for use in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Further validation to support clinical translation of [(18)F]FTC-146 for imaging sigma-1 receptors. Shen, B., James, ML., Andrews, L., et al.[2022]

In a study involving 226 participants matched from two longitudinal cohort studies, 18F-MK6240 demonstrated a higher sensitivity to changes in tau levels compared to 18F-flortaucipir (FTP), particularly in preclinical Alzheimer's disease stages.

Both tracers effectively distinguished between clinical groups at baseline, but only 18F-MK6240 showed a significant increase in tau levels in Aβ+ cognitively unimpaired individuals, suggesting its potential as a more effective marker for drug efficacy in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-Sectional and Longitudinal Comparison of Tau Imaging with 18F-MK6240 and 18F-Flortaucipir in Populations Matched for Age, MMSE and Brain Beta-Amyloid Burden. Bourgeat, P., Krishnadas, N., Doré, V., et al.[2023]

The study evaluated two tau tracers, [(18)F]T808 and [(18)F]T807, showing that they have high brain uptake but no specific binding in models of tau pathology, indicating potential limitations in their use for detecting tau in Alzheimer's disease.

Comparative analysis of these tracers against eight new tau ligands revealed that [(18)F]T808 demonstrated over 50% selective blocking in human Alzheimer disease slices, providing valuable insights for developing more effective tau imaging agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807. Declercq, L., Celen, S., Lecina, J., et al.[2018]

In a study involving 309 cognitively normal subjects, it was found that the hemispheric white matter (hemisWM) significantly contributes to spill-in effects in [18F]Flortaucipir PET imaging, impacting the quantification of tau pathology in target brain regions.

Partial volume correction (PVC) methods, including a simple two-compartment approach, effectively reduced the impact of spill-in effects, but some correlations between target and off-target regions remained, indicating potential biological or tracer-related factors at play.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of spill-in counts from off-target regions on [18F]Flortaucipir PET quantification. López-González, FJ., Costoya-Sánchez, A., Paredes-Pacheco, J., et al.[2022]

The synthesized radioligand [18F]15 shows strong potential for PET imaging of mGluR4 in the brain, demonstrating good affinity and selectivity, along with sufficient metabolic stability.

In PET imaging studies with male Sprague Dawley rats, [18F]15 effectively accumulated in brain regions expressing mGluR4, indicating its efficacy for visualizing this receptor in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and Characterization of Fluorine-18-Labeled N-(4-Chloro-3-((fluoromethyl-d2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain. Wang, J., Qu, X., Shoup, TM., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Further validation to support clinical translation of [(18)F]FTC-146 for imaging sigma-1 receptors. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cross-Sectional and Longitudinal Comparison of Tau Imaging with 18F-MK6240 and 18F-Flortaucipir in Populations Matched for Age, MMSE and Brain Beta-Amyloid Burden. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807. [2018]

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

Impact of spill-in counts from off-target regions on [18F]Flortaucipir PET quantification. [2022]

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

Synthesis and Characterization of Fluorine-18-Labeled N-(4-Chloro-3-((fluoromethyl-d2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain. [2021]