Danuglipron for Obesity

No longer recruiting at 2 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Disqualifiers: Significant medical conditions, Drug absorption issues, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 20-23 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine, danuglipron, as a potential treatment for obesity. It aims to understand how the body absorbs danuglipron and how it interacts with other medicines like atorvastatin and rosuvastatin. The study targets adults who are overweight or obese, focusing on the safety and tolerability of danuglipron. Participants will be divided into four groups, each testing different combinations of these medicines over several months. Suitable candidates for the trial have a body mass index (BMI) of 25 or higher and weigh over 110 pounds. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants should not have any conditions affecting drug absorption or known allergies to certain drugs used in the study.

Is there any evidence suggesting that danuglipron is likely to be safe for humans?

Research shows that danuglipron may be safe to use, but certain considerations are important. Studies have found that while it can aid in weight loss, some people discontinued its use due to side effects. Although these side effects aren't specified, the fact that some participants chose to stop suggests they might be bothersome.

In earlier studies, danuglipron was tested at different doses, and the side effects mostly aligned with researchers' expectations, indicating they are likely manageable. Importantly, no serious health problems have been reported in the available data.

Since danuglipron remains in the early stages of human testing, researchers are closely monitoring its safety. Prospective trial participants should weigh the potential benefits against the possibility of experiencing side effects that some have encountered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about Danuglipron for obesity because it brings something fresh to the table compared to current treatments. Unlike standard options like lifestyle changes, surgery, or medications such as orlistat and phentermine, Danuglipron targets a different mechanism. It works by acting on the GLP-1 receptor, which plays a role in regulating appetite and metabolism, potentially offering a more effective way to manage weight. Additionally, the trial explores its combination with statins like atorvastatin and rosuvastatin, which could enhance its effects on metabolic health. This unique approach could provide a new avenue for treating obesity, offering hope for better outcomes.

What evidence suggests that danuglipron might be an effective treatment for obesity?

Research shows that danuglipron can help people lose weight. In earlier studies, participants taking danuglipron lost between 5% and 13% of their body weight over 26 to 32 weeks. These results surpassed those of participants taking a placebo, a pill with no active medicine. The treatment proved to be safe and easy to tolerate. This evidence suggests that danuglipron could be an effective option for weight loss in individuals who are overweight or obese. Participants in this trial will receive multiple oral doses of danuglipron, with some cohorts also receiving a single dose of atorvastatin or rosuvastatin to evaluate the combined effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18 to less than 65 who are overweight or obese, with a BMI of ≥25.0-45.4 kg/m2 and weigh more than 110 pounds. It's not specified who can't join the trial.

Inclusion Criteria

My BMI is between 25.0 and 45.4, and I weigh more than 110 lbs.

Exclusion Criteria

I am allergic to GLP-1R agonists or certain cholesterol medications.

I have no significant medical conditions or abnormal lab results.

I have a condition that might affect how drugs are absorbed in my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple oral doses of danuglipron with and without atorvastatin or rosuvastatin

20-23 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Danuglipron

Trial Overview The study investigates how danuglipron is absorbed into the blood after multiple doses in overweight/obese individuals and if it affects how the body processes statins like Atorvastatin and Rosuvastatin over approximately 5.5 to 6 months.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 2 Interventions

Participants will receive a single dose of rosuvastatin and multiple oral doses of danuglipron with and without rosuvastatin

Group II: Cohort 3 Experimental Treatment 2 Interventions

Participants will receive a single dose of atorvastatin and multiple oral doses of danuglipron with and without atorvastatin

Group III: Cohort 2 Experimental Treatment 2 Interventions

Participants will receive a single dose of rosuvastatin and multiple oral doses of danuglipron with and without rosuvastatin

Group IV: Cohort 1 Experimental Treatment 2 Interventions

Participants will receive a single dose of atorvastatin and multiple oral doses of danuglipron with and without atorvastatin

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study involving 44 subjects with varying degrees of obesity, desopimon demonstrated a strong appetite-inhibiting effect in 41 patients, leading to an average weight loss of 12.9 kg over six weeks, primarily from fat reduction.

The treatment was well-tolerated with minimal side effects, and it showed beneficial changes in serum triglycerides and free fatty acids, suggesting its potential as an effective adjunct therapy for hyperphagic obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Desopimon in the treatment of obesity]. Balabanski, L., Tashev, T., Meretev, A., et al.[2013]

The metabolite (+)-norfenfluramine, derived from the weight-loss drug (+)-fenfluramine, can cause significant contraction of arterial smooth muscle through activation of 5-HT(2A) receptors, indicating a mechanism for its vasoactive properties.

In conscious rats, (+)-norfenfluramine led to a dose-dependent increase in mean arterial blood pressure, which was largely blocked by the 5-HT(2A) receptor antagonist ketanserin, highlighting its potential to raise blood pressure and suggesting caution in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fenfluramine metabolite (+)-norfenfluramine is vasoactive. Ni, W., Li, MW., Thakali, K., et al.[2017]

Several anti-obesity drugs are in clinical development, including centrally-acting drugs like radafaxine and rimonabant, which has completed phase III trials, indicating it is the most advanced in testing.

Other drug categories being explored target satiety signals and fat absorption, such as glucagon-like peptide-1 drugs (like liraglutide) and lipase inhibitors (like cetilistat), showing a diverse approach to obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity drugs in clinical development. Halford, JC.[2022]

Sibutramine and orlistat are two FDA-approved medications for long-term obesity treatment, with distinct mechanisms of action: sibutramine acts as a reuptake inhibitor of monoamines, while orlistat inhibits pancreatic lipase to reduce fat absorption.

Dexfenfluramine has been withdrawn from the market due to its association with serious heart valve issues, highlighting the importance of safety monitoring in obesity pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress in obesity pharmacotherapy. Ryan, DH.[2019]

A case-control study involving 681 patients found that the use of benfluorex was significantly associated with unexplained mitral regurgitation, with an odds ratio of 17.1, indicating a strong link between the drug and this heart condition.

Out of 27 cases of unexplained mitral regurgitation, 19 were users of benfluorex, compared to only 3 out of 54 matched controls, highlighting the potential cardiac risks associated with this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benfluorex and unexplained valvular heart disease: a case-control study. Frachon, I., Etienne, Y., Jobic, Y., et al.[2021]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-announces-topline-phase-2b-results-oral-glp-1r

Pfizer Announces Topline Phase 2b Results of Oral GLP ... Danuglipron demonstrated mean placebo-adjusted weight reductions ranging from -8% to -13% at 32 weeks and -5% to -9.5% at 26 weeks While ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40539310/

Efficacy and safety of danuglipron (PF-06882961) in adults ... Danuglipron resulted in statistically significant and clinically meaningful reductions in body weight versus placebo over 26 or 32 weeks.

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/eli-lilly-orforglipron-first-phase-iii-win/

Eli Lilly's shares up as oral GLP-1RA scores in first Phase ... Eli Lilly's Phase III trial with its oral weight loss pill, orforglipron, has met its primary endpoint, reducing A1C levels by up to 1.6%.

4. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-advances-development-once-daily-formulation-oral-glp

Pfizer Advances Development of Once-Daily Formulation ... The most advanced of them, danuglipron, has demonstrated good efficacy ... “Following a thorough analysis of our previous Phase 2b data and trial ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12326921/

Efficacy and safety of danuglipron (PF‐06882961) in adults ... Overall, the outcomes of this Phase 2b study demonstrate the efficacy of danuglipron at target doses of 40–200 mg BID in participants with obesity, relative to ...

6. clinicaltrialsarena.com clinicaltrialsarena.com/features/obesity-trials-to-watch/

Obesity: Six trials to watch over the next 12 months The trial is evaluating the efficacy and safety of the drug in adults with obesity. Danuglipron tromethamine is another pipeline drug that ...

7. semanticscholar.org semanticscholar.org/paper/Efficacy-and-safety-of-danuglipron-%28PF%E2%80%9006882961%29-in-Buckeridge-Cobain/c45186e8582e67af976ecc9696cd8bce674cf99e

Efficacy and safety of danuglipron (PF‐06882961) in adults ... The overall safety profile observed in this study was consistent with expectations for the mechanism, although discontinuation rates due to AEs were higher ...