NNC0487-0111 Formulations for Obesity

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Disqualifiers: Vitamin D deficiency, High HbA1c, others

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

Compensation: Varies

Number of Visits: 306

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new medication, NNC0487-0111 (also known as Amycretin), for weight control in individuals who are overweight or have obesity. The trial aims to determine how two different tablet formulations work in the body and whether taking them with a meal affects their effectiveness. Participants will randomly receive either Formulation C or Formulation D. This trial may suit individuals with a Body Mass Index (BMI) between 27 and 39.9 who are managing overweight or obesity. As a Phase 1 trial, participants will be among the first to help researchers understand how this new treatment works in people.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. Please consult with the trial investigator for guidance.

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

Research shows that the treatment NNC0487-0111, also known as amycretin, has been tested in people and appears safe and well-tolerated. Earlier studies with individuals who are overweight or have obesity revealed a safety profile similar to other treatments in its category. Participants did not experience any major side effects that would cause concern.

This treatment is currently in the early stages of clinical trials. These early trials aim to ensure a treatment's safety before progressing to larger studies. The presence of NNC0487-0111 in these early stages suggests it has shown enough promise in initial safety tests to warrant further study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NNC0487-0111 for obesity because it introduces a unique approach with its two formulations, C and D. Unlike most current obesity treatments that often involve lifestyle changes, medications like orlistat, or hormone-based injections, NNC0487-0111 is designed to be taken once daily, potentially improving convenience and compliance. Its distinct mechanism of action might offer an alternative pathway to weight management by targeting specific physiological processes. Additionally, the trial explores different dose levels, which could help pinpoint the most effective and safe dosage for individuals, offering a potentially tailored treatment approach.

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

Research shows that the drug NNC0487-0111, also known as amycretin, may aid in weight loss. Studies found that participants taking amycretin lost significantly more weight than those on a placebo, with an average weight loss of 13.1%. This trial will evaluate different formulations of NNC0487-0111. The treatment mimics two hormones, GLP-1 and amylin, which help regulate appetite and food intake. Amycretin's safety profile is similar to other treatments targeting these hormones, making it a promising option for managing obesity. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

This trial is for individuals living with overweight or obesity. Participants must be willing to undergo two phases of the study, taking different oral formulations of a weight control medicine called NNC0487-0111. Specific eligibility criteria are not provided, but typically participants should be in stable health and meet certain body weight or BMI requirements.

Inclusion Criteria

Body mass index (BMI) between 27.0 and 39.9 kilogram per meter square (kg/m^2)

I am either male or female.

My health, heart function, and lab tests meet the study's requirements.

Exclusion Criteria

Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol

Any laboratory safety parameters at screening outside specified ranges

Vitamin D (25-hydroxycholecalciferol) less than 12 ng/mL (30 Nanometer (nM)) at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase A

Participants receive once daily dose of six different dose levels of NNC0487-0111 at increasing doses, with dose escalation every 3 weeks

18 weeks

Visits on days 21, 42, 63, 84, 105, and 126

Phase B

Participants receive once daily dose of NNC0487-0111 to test the effect of food intake on pharmacokinetics

4 weeks

Visit on day 132

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

End of study visit on day 153

What Are the Treatments Tested in This Trial?

Interventions

• NNC0487-0111

Trial Overview The study tests two different tablet formulations (C and D) of NNC0487-0111, assessing how they behave in the body and their effectiveness when taken with or without food. The trial randomly assigns one of these formulations to each participant over a period of approximately 5-6 months.

How Is the Trial Designed?

Group I: Phase B: NNC0487-0111 (formulation D) Experimental Treatment 1 Intervention

Participants will receive once daily dose of dose level 6 of NNC0487-0111 (formulation D).

Group II: Phase A: NNC0487-0111 (formulation D) Experimental Treatment 1 Intervention

Participants will receive once daily dose of six different dose levels (1-6) of NNC0487-0111 (formulation D) at increasing doses (the dose will be escalated every 3 weeks).

Group III: Phase B: NNC0487-0111 (formulation C) Active Control 1 Intervention

Participants will receive once daily dose of dose level 6 of NNC0487-0111 (formulation C).

Group IV: Phase A: NNC0487-0111 (formulation C) Active Control 1 Intervention

Participants will receive once daily dose of six different dose levels (1-6) of NNC0487-0111 (formulation C) at increasing doses (the dose will be escalated every 3 weeks).

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Published Research Related to This Trial

Long-acting amylin analogues, like cagrilintide, are being developed as potential treatments for obesity, showing promising weight-reducing effects in early clinical studies.

These analogues work by activating amylin and calcitonin receptors, which help control energy balance and body weight, but further research is needed to confirm their long-term effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting amylin analogues for the management of obesity. Mathiesen, DS., Bagger, JI., Knop, FK.[2023]

The review summarizes existing pharmaceutical treatments for obesity and highlights the importance of gut peptides in regulating energy balance, suggesting they could lead to new therapies.

It also discusses ongoing development of new obesity medications, indicating a promising future for more effective treatments based on these mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The obesity pipeline: current strategies in the development of anti-obesity drugs. Cooke, D., Bloom, S.[2006]

Amylin analogues, like pramlintide, show promise as anti-obesity medications by promoting satiety, slowing gastric emptying, and leading to significant weight loss, making them potential treatments for obesity.

The investigational drug AM833 (cagrilintide) is a long-acting amylin analogue that has demonstrated a dose-dependent reduction in food intake and significant weight loss, highlighting its potential as a novel treatment for obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amylin as a Future Obesity Treatment. Dehestani, B., Stratford, NR., le Roux, CW.[2022]

Obesity is a growing epidemic, with over 4 million deaths annually, highlighting the urgent need for safer and more effective treatments beyond current options like Orlistat, which can cause liver and kidney toxicity.

Recent patents from 2010 to 2021 indicate a focus on natural compositions, including plant extracts and nanoparticles, as potential anti-obesity therapies, particularly from countries like China, South Korea, the United States, and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanistically acting anti-obesity compositions/formulations of natural origin: a patent review (2010-2021). Sengupta, P., Tiwari, N., Bhatt, T., et al.[2022]

Currently, four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release, and naltrexone/bupropion extended release, each with evidence supporting their safety and efficacy.

The review highlights ongoing development of new monotherapies and combination products that could enhance treatment options for obesity, addressing a significant public health crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment of obesity: current status and future prospects. Kakkar, AK., Dahiya, N.[2022]

In a study involving 1187 obese adults over 2 years, orlistat combined with a dietary intervention led to significantly greater weight loss compared to a placebo, with orlistat-treated subjects losing an average of 8.76 kg versus 5.81 kg for placebo (P<.001).

Orlistat at a dosage of 120 mg three times a day not only helped subjects regain less weight during the second year (3.2 kg regain) compared to lower doses and placebo but also improved levels of low-density lipoprotein cholesterol and insulin, indicating potential cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. Davidson, MH., Hauptman, J., DiGirolamo, M., et al.[2022]

Three FDA-approved medications for long-term obesity treatment—sibutramine, orlistat, and rimonabant—have shown significant weight loss benefits in large clinical trials lasting 2 to 4 years, with average weight loss of 8%-10% compared to 4%-6% for placebo.

While all medications have side effects, sibutramine can increase blood pressure and heart rate, orlistat can cause gastrointestinal issues like steatorrhea, and rimonabant generally has a favorable safety profile with mild, self-limited nausea and gastrointestinal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment of the overweight patient. Bray, GA., Ryan, DH.[2018]

Obesity is a major health issue in Western countries, causing approximately 300,000 deaths annually in the U.S. and increasing the risk for various diseases, including liver disease and colon cancer.

Effective management of obesity includes lifestyle changes, and in some cases, medications or surgery, with a target of losing 10% of body weight within 6 months; currently, only two medications, sibutramine and orlistat, are approved for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical management of obesity. Kushner, RF.[2005]

Obesity is linked to serious health issues like type 2 diabetes and cardiovascular disease, and pharmacotherapy is recommended when lifestyle changes alone do not lead to weight loss in patients with a BMI of 25 kg/m2 or higher.

The paper reviews available long-term anti-obesity medications, which include centrally acting anorexiants and peripherally acting drugs like orlistat, highlighting the need for individualized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Long-Term Pharmacotherapies for the Management of Obesity. Kim, BY., Kang, SM., Kang, JH., et al.[2020]

Recent advancements in peptide chemistry have led to the development of effective anti-obesity drugs that target appetite regulation and energy metabolism, showing fewer side effects compared to older medications.

Liraglutide, originally an antidiabetic drug, has been successfully repurposed as an anti-obesity treatment, highlighting the potential of peptide-based therapies in managing obesity-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of feeding and therapeutic application of bioactive peptides. Ueno, H., Zhang, W., Nakazato, M.[2022]

A comprehensive analysis of the FDA Adverse Event Reporting System revealed 18,675 unique adverse event reports linked to anti-obesity medications (AOMs) among 15,143 patients, highlighting significant safety concerns.

Serious adverse events included a fatality ratio of 4.9%, with cardiovascular complications being particularly prevalent, accounting for 31% of AEs related to phentermine, and indicating a need for ongoing safety monitoring of AOMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. Alsuhibani, A., Alrasheed, M., Gari, M., et al.[2022]

Orlistat, a medication used to treat obesity, can potentially cause acute pancreatitis, as demonstrated in two case reports where patients experienced severe abdominal pain and elevated pancreatic enzymes shortly after starting the drug.

Healthcare providers should be cautious when prescribing orlistat, especially to patients with a history of pancreatic injury, and consider pancreatitis as a possible diagnosis for patients who develop abdominal pain after beginning treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute pancreatitis following orlistat therapy: report of two cases. Ahmad, FA., Mahmud, S.[2018]

Orlistat, an intestinal lipase inhibitor, has been shown to significantly aid in weight loss when combined with a low-fat diet, with patients losing more initial body weight compared to those on a placebo in randomized trials.

After 24 months, more than 5% weight loss was maintained in a greater number of patients treated with orlistat, leading to significant reductions in cardiovascular risk factors, although it may cause fat malabsorption and potential deficiencies in fat-soluble vitamins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review article: malnutrition and maltreatment--a comment on orlistat for the treatment of obesity. Cahill, A., Lean, ME.[2019]

Lifestyle changes like diet, exercise, and behavioral therapy are essential for treating obesity, and if these do not lead to a 5% weight loss in 3 to 6 months, medications may be considered for patients with a BMI of 30 or higher, or 27 with related health issues.

Current obesity medications like orlistat, sibutramine, and rimonabant can lead to moderate weight loss and improved cardiovascular health, particularly enhancing glucose metabolism, but their side effects must be carefully evaluated before use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. Hamann, A.[2021]

Citations

1. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01185-7/abstract

results from a phase 1b/2a randomised controlled study The aim of this study was to investigate the safety, tolerability, pharmacokinetics, and effects on bodyweight of subcutaneous amycretin ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625011857

Amycretin, a novel, unimolecular GLP-1 and amylin ... In people with overweight or obesity, once-weekly subcutaneous amycretin up to 60 mg had a safety and tolerability profile consistent with GLP-1 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05369390

A Research Study on How NNC0487-0111 Works in ... This study also look at how the study medicine affects body weight and how to improve the treatment of people with overweight, obesity or related diseases. This ...

4. prnewswire.com prnewswire.com/news-releases/novo-nordisk-advances-early-stage-obesity-medication-amycretin-to-phase-3-clinical-development-based-on-early-phase-clinical-trial-results-in-people-with-obesity-or-excess-weight-published-in-the-lancet-302487500.html

Novo Nordisk advances early-stage obesity medication ... Exploratory results showed participants taking 100 mg per day of oral amycretin achieved a mean weight loss of 13.1% versus 1.2% with placebo ...

5. hcplive.com hcplive.com/view/amycretin-data-at-ada-highlight-efficacy-safety-of-dual-agonist-obesity-therapy

Amycretin Data at ADA Highlight Efficacy, Safety of Dual- ... New research reveals amycretin's promising potential for weight loss in obesity treatment, advancing to phase 3 trials for effective management options.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40550229/

a first-in-human, phase 1, double-blind, randomised ... Interpretation: In people with overweight or obesity, amycretin appeared safe and tolerable. Results from this first-in-human, phase 1 study ...