Belzutifan + Metformin for Healthy Subjects

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Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Metformin

Disqualifiers: Cancer, Anemia, Acidosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the drug belzutifan affects the levels of metformin in healthy individuals. Participants will first take metformin alone, then take it again with belzutifan to observe changes in metformin's presence in the blood and urine. The trial seeks non-smokers who can swallow pills and have no recent history of cancer or specific blood or metabolic issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves taking metformin and belzutifan, it's best to discuss your current medications with the trial team to ensure there are no interactions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that belzutifan has been studied for conditions like kidney tumors. In these studies, belzutifan was generally well-tolerated, though some patients reported side effects such as tiredness and low red blood cell counts. It's important to note that these studies involved people with health conditions, not healthy volunteers.

Metformin is a medication commonly used to manage diabetes. It has a long history of safe use and is generally well-tolerated by most people. Some may experience mild side effects like an upset stomach, but these often decrease over time.

This is a Phase 1 trial, meaning researchers are primarily assessing the safety of these treatments in healthy people. This phase involves careful monitoring for any side effects. While belzutifan is not yet approved for use in healthy individuals, its use in other conditions provides some background on its safety. Metformin’s established safety record for diabetes offers reassurance about its use in this study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about belzutifan combined with metformin because it offers a novel approach by targeting the HIF-2α pathway, which is different from the mechanisms of traditional treatments. Most treatments for conditions related to abnormal cellular oxygen sensing focus on other pathways or mechanisms. Belzutifan acts directly on the hypoxia-inducible factor (HIF) pathway, potentially offering new benefits in managing conditions like certain cancers or metabolic disorders. Additionally, the combination with metformin, a well-known diabetes medication, might enhance its effectiveness and provide broader therapeutic benefits. This dual action could lead to innovative strategies for tackling complex health issues more efficiently.

What evidence suggests that this trial's treatments could be effective?

Research has shown that belzutifan, a type of medication, produces promising results in treating certain rare tumors, with 26% of patients experiencing tumor shrinkage. Metformin, commonly used to control blood sugar, might enhance the effects of other treatments. Evidence suggests that combining metformin with other drugs can improve outcomes for cancers such as lung, colorectal, and prostate. In this trial, some participants will receive metformin alone, while others will receive a combination of belzutifan and metformin. Although the current study involves healthy participants, researchers are exploring the combination of belzutifan and metformin for potential benefits in various medical conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This clinical trial is for healthy adults who can safely take metformin and belzutifan. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and not be on conflicting medications.

Inclusion Criteria

Is a continuous non-smoker for at least 3 months prior to dosing

Has body mass index (BMI) ≥ 18.0 and ≤ 42.0 kg/m2

Is able to swallow multiple tablets

Exclusion Criteria

I have had anemia in the past 5 years.

Has a pulse oximetry reading less than 92% at rest

I have had cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Period 1: Metformin Administration

Participants receive a single dose of metformin and pharmacokinetics are studied

1 day

1 visit (in-person)

Period 2: Belzutifan with Metformin

Belzutifan is administered daily for 5 days with a single dose of metformin on Day 4

5 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belzutifan
• Metformin

Trial Overview

The study investigates how belzutifan affects the levels of metformin in the body over time. Participants will first take only metformin, then combine it with belzutifan to compare blood and urine levels of the drug.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

On Day 1 of Period 1, a single dose of metformin will be administered.

Group II: Belzutifan with Metformin Experimental Treatment 2 Interventions

In Period 2, belzutifan will be administered every day for 5 consecutive days with a single dose of metformin coadministered on Day 4.

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

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07121959

A Study of Belzutifan (MK-6482) and Metformin in Healthy ...

Study Overview. The goal of this study is to learn how belzutifan (MK-6482) affects the levels of metformin in a healthy person's body over time. Researchers ...

2.

withpower.com

withpower.com/trial/phase-1-healthy-subjects-hs-7-2025-cd371

Belzutifan + Metformin for Healthy Subjects

The goal of this study is to learn how belzutifan (MK-6482) affects the levels of metformin in a healthy person's body over time.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10836959/

Metformin Regulates the miR-205/VEGFA Axis in Renal ...

There is increasing evidence that combining MF and antineoplastic agents may improve outcomes of patients suffering from lung [2], colorectal, and prostate ...

4.

news-medical.net

news-medical.net/news/20251018/Belzutifan-demonstrates-strong-clinical-activity-in-two-rare-neuroendocrine-tumors.aspx

Belzutifan demonstrates strong clinical activity in two rare ...

The trial demonstrated that the HIF-2α inhibitor belzutifan showed meaningful antitumor activity with a 26% objective response rate, a ...

5.

ema.europa.eu

ema.europa.eu/en/documents/assessment-report/welireg-epar-public-assessment-report_en.pdf

Welireg - belzutifan - European Medicines Agency

with data from the Study 004. Data were available from 61 patients and the analyses included results up to. Week 13. Based on these results ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12483163/

The safety profile of belzutifan in renal tumors - PubMed Central

The efficacy and side effects of belzutifan are well-documented from clinical trials; however, real-world data examining the incidence and ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01442870

Evaluation of Clinical Safety of Combining Metformin With ...

Study Details | NCT01442870 | Evaluation of Clinical Safety of Combining Metformin With Anticancer Chemotherapy | ClinicalTrials.gov.