NNC0487-0111 Formulations for Obesity

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Novo Nordisk A/S

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study consists of two phases: Phase A and Phase B. Participants are being asked to participate in both phases. Phase A of this study is comparing two formulations of a study medicine called NNC0487-0111 for weight control in people with overweight or obesity. Phase B of this study is testing how taking NNC0487-0111 at the same time as a meal affects the way NNC0487-0111 works in participants body. The aim of this study is to compare how two different formulations of NNC0487-0111 behave in the body, and how their function is affected when they are taken with or without a meal. Participants will either get NNC0487-0111 Formulation C, or NNC0487-0111 Formulation D. Both formulations are given as tablets. Which treatment participants get is decided by chance. Oral NNC0487-0111 is a new medicine which cannot be prescribed by doctors but has previously been tested in humans. The study will last for about 5 - 6 months (155-184 days).

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.

What data supports the idea that the drug NNC0487-0111 Formulations for Obesity is an effective treatment?

The available research does not provide specific data on the effectiveness of NNC0487-0111 Formulations for Obesity. Instead, it discusses other drugs like orlistat, sibutramine, and rimonabant, which have shown moderate weight reduction and improvements in health conditions related to obesity. Without specific data on NNC0487-0111, we cannot compare its effectiveness to these other treatments. ^{1 2 3 4 5}

What safety data is available for the obesity treatment NNC0487-0111?

The provided research does not contain specific safety data for NNC0487-0111 or its other names (Amycretin, NN-9487, NN9487, NNC-04870111). The articles discuss general safety concerns and adverse events associated with anti-obesity medications, including cardiovascular and kidney complications, but do not mention NNC0487-0111 specifically. Further investigation into clinical trial data or specific studies on NNC0487-0111 would be necessary to obtain detailed safety information. ^{6 7 8 9 10}

Is the drug NNC0487-0111 a promising treatment for obesity?

Yes, NNC0487-0111, also known as Amycretin, is a promising drug for obesity. It is an amylin analogue, which means it mimics a natural hormone that helps control appetite and food intake. This drug can help reduce food intake and lead to significant weight loss, making it a potential new option for people struggling with obesity. ^{10 11 12 13 14}

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

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

I am either male or female.

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

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

Exclusion Criteria

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

Parathyroid hormone (PTH) outside normal range at screening

Total calcium outside normal range at screening

Treatment Details

Interventions

• NNC0487-0111 (Other)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. [2021]

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

Drug treatment of the overweight patient. [2018]

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

Medical management of obesity. [2005]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Current Long-Term Pharmacotherapies for the Management of Obesity. [2020]

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

Mechanistically acting anti-obesity compositions/formulations of natural origin: a patent review (2010-2021). [2022]

7. Netherlands 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. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Drug treatment of obesity: current status and future prospects. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

Acute pancreatitis following orlistat therapy: report of two cases. [2018]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Amylin as a Future Obesity Treatment. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Long-acting amylin analogues for the management of obesity. [2023]

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

Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Regulation of feeding and therapeutic application of bioactive peptides. [2022]

14. England pubmed.ncbi.nlm.nih.gov

The obesity pipeline: current strategies in the development of anti-obesity drugs. [2006]