LY3971297 for Obesity

Recruiting at 4 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must be taking: Antihypertensives, ACE inhibitors

Must not be taking: Phosphodiesterase inhibitors, Beta blockers

Disqualifiers: Cardiovascular, Renal, Psychiatric, others

Compensation: Varies

Number of Visits: Unknown

Duration: 60-90 days

225 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called LY3971297, which is given as an injection under the skin. The study includes both healthy people and obese people with high blood pressure. Researchers will take blood samples to see how much of the drug enters the bloodstream and how long it stays in the body.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, for Part D, participants must have a stable dose of antihypertensive medications, and for Part G, participants can continue stable treatments for hypertension, type 2 diabetes, dyslipidemia, and hypothyroidism. Some medications like phosphodiesterase 5 inhibitors, long-acting nitrates, nitric oxide donors, and beta blockers are not allowed for Parts D and G.

What data supports the effectiveness of the treatment LY3971297, LA-ANP, Long-Acting Atrial Natriuretic Peptide for obesity?

Research suggests that atrial natriuretic peptide (ANP) levels are linked to obesity, and weight loss can increase ANP levels, which may help with reducing body fat. This implies that treatments involving ANP could potentially aid in managing obesity. ^{1 2 3 4 5}

How is the drug LY3971297 unique for treating obesity?

LY3971297, a long-acting atrial natriuretic peptide, is unique because it may help with weight loss by increasing the levels of a natural hormone that promotes the removal of excess salt and water from the body, potentially aiding in reducing body fat and improving heart health, which is different from many other obesity treatments that focus on appetite suppression or calorie absorption. ^{3 4 5 6 7}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

This trial is for healthy individuals or those with obesity and high blood pressure. Healthy participants should have a BMI of 18.5 to 35 kg/m2, while obese participants need a BMI of 30 to 40 kg/m2 and meet specific waist measurements. Certain parts require Chinese or Japanese descent. Participants must not have significant health issues, psychiatric disorders, risky blood pressures, recent large blood donations, heavy nicotine or alcohol use, nor take certain medications.

Inclusion Criteria

I am a man who agrees to follow contraception rules or a woman who cannot become pregnant.

I have obesity and high blood pressure, and my medication dose has been stable for the last 3 months.

I am obese with a BMI between 30-40 and my waist is at least 102 cm (men) or 89 cm (women).

Exclusion Criteria

I am using or plan to use long-acting nitrates or nitric oxide donors.

I am using or plan to use medications like Viagra or Cialis.

I have been diagnosed with a significant drop in blood pressure upon standing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single or multiple ascending doses of LY3971297 or placebo administered subcutaneously or intravenously

60-90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent adverse events and pharmacokinetics

4-8 weeks

Treatment Details

Interventions

• LY3971297

Trial Overview The study tests LY3971297 injections in different groups: healthy people and those with obesity plus high BP. It checks the drug's safety profile by observing side effects and measures how it's absorbed and cleared from the body over approximately two to three months.

Participant Groups

Group I: LY3971297 (Part G) Experimental Treatment 1 Intervention

Multiple doses of LY3971297 administered SC

Group II: LY3971297 (Part F) Experimental Treatment 1 Intervention

Single doses of LY3971297 administered intravenously (IV) in healthy participants

Group III: LY3971297 (Part E) Experimental Treatment 1 Intervention

Multiple doses of LY3971297 administered SC in healthy Japanese participants

Group IV: LY3971297 (Part D) Experimental Treatment 1 Intervention

Multiple ascending doses of LY3971297 administered SC

Group V: LY3971297 (Part C) Experimental Treatment 1 Intervention

Multiple ascending doses of LY3971297 administered SC in healthy Chinese participants

Group VI: LY3971297 (Part B) Experimental Treatment 1 Intervention

Multiple ascending doses of LY3971297 administered SC in healthy participants

Group VII: LY3971297 (Part A) Experimental Treatment 1 Intervention

Single ascending doses of LY3971297 administered subcutaneously (SC) in healthy participants

Group VIII: Placebo (Part A, B, C, D, E, & G) Placebo Group 1 Intervention

Placebo administered SC

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

A 6-month hypocaloric diet led to an average weight loss of 9.1 kg in overweight or obese patients, which improved various health markers like insulin resistance and blood pressure, but did not significantly change resting levels of atrial natriuretic peptide (ANP).

Exercise increased ANP release in these patients, suggesting that while weight loss affects how ANP is cleared from the body, regular physical activity is crucial for enhancing ANP levels, indicating that combining diet and exercise may be the best approach to address natriuretic peptide deficiencies associated with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients. Haufe, S., Kaminski, J., Utz, W., et al.[2018]

In a study of 2038 patients presenting with acute dyspnoea, adjusting the NT-proBNP cut-off levels for obesity improved the sensitivity for diagnosing acute heart failure (AHF) from 96.7% to 98.2%, allowing for better identification of patients at risk.

Lowering NT-proBNP cut-offs based on body mass index (BMI) also reduced the number of patients remaining in the 'gray zone' for diagnosis, enhancing the clinical utility of NT-proBNP in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effect of obesity on N-terminal pro-B-type natriuretic peptide cut-off concentrations for the diagnosis of acute heart failure. Kozhuharov, N., Martin, J., Wussler, D., et al.[2023]

In an experimental study with obese rats, a 15-week caloric restriction led to a 40% reduction in body weight, which significantly increased circulating levels of atrial natriuretic peptide (ANP) and reduced adipocyte size.

Despite weight loss normalizing body fat, the rats still showed signs of cardiac hypertrophy, indicating that obesity can have lasting effects on heart structure, but the increased ANP may help promote diuresis and sodium balance during weight reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of experimental obesity and subsequent weight reduction upon circulating atrial natriuretic peptide. Crandall, DL., Ferraro, GD., Cervoni, P.[2020]

In a study of 2203 participants aged 30 and older, higher levels of plasma proANP1-98 were significantly associated with an increased risk of central obesity, with odds ratios indicating a clear dose-response relationship.

The findings suggest that elevated plasma proANP1-98 may serve as a marker or risk factor for central obesity, challenging the previously understood link between lower ANP levels and obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma proANP1-98 levels are positively associated with central obesity: A cross-sectional study in a general population of China. Zhu, Z., Zhang, Q., Peng, H., et al.[2018]

In a study of 693 healthy Scandinavian subjects, plasma pro-atrial-derived natriuretic peptide (proANP) concentrations were found to be unaffected by body mass index (BMI) and plasma glucose levels in fasting individuals, suggesting that proANP may not be a reliable biomarker for obesity or type 2 diabetes in this population.

The research introduced an optimized assay for measuring low concentrations of proANP, which could be useful for future studies investigating its role in conditions like obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose. Mark, PD., Hunter, I., Terzic, D., et al.[2017]

In a study involving 77 participants (26 obese hypertensives, 26 obese normotensives, and 25 lean hypertensives), levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were found to be useful markers for identifying preclinical cardiac disease in obese individuals, particularly in relation to left ventricular (LV) diastolic dysfunction and hypertrophy.

ANP levels were higher in patients with LV diastolic dysfunction, while BNP levels were elevated in those with both LV hypertrophy and diastolic dysfunction, indicating that these peptides can help assess cardiac health in obese patients regardless of their blood pressure status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natriuretic peptides as markers of preclinical cardiac disease in obesity. Grandi, AM., Laurita, E., Selva, E., et al.[2015]

In a study of 100 patients undergoing left heart catheterization, obese individuals (BMI ≥ 30 kg/m²) were found to have significantly lower levels of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) compared to nonobese individuals (BMI < 30 kg/m²).

The findings suggest that lower circulating levels of these natriuretic peptides in obese patients may play a role in the development of heart failure, highlighting a potential mechanism linking obesity to heart health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obese patients have lower B-type and atrial natriuretic peptide levels compared with nonobese. Khush, KK., Gerber, IL., McKeown, B., et al.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Clinical effect of obesity on N-terminal pro-B-type natriuretic peptide cut-off concentrations for the diagnosis of acute heart failure. [2023]

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

Effect of experimental obesity and subsequent weight reduction upon circulating atrial natriuretic peptide. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Plasma proANP1-98 levels are positively associated with central obesity: A cross-sectional study in a general population of China. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Natriuretic peptides as markers of preclinical cardiac disease in obesity. [2015]

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

Obese patients have lower B-type and atrial natriuretic peptide levels compared with nonobese. [2019]