NNC0487-0111 for Obesity

Recruiting at 1 trial location

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Disqualifiers: Diabetes, Vitamin D deficiency, others

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

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new medicine called NNC0487-0111 that mimics natural hormones to help people feel full. It aims to help those who are overweight or obese manage their weight. The study will check if the medicine is safe and how it affects body weight.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial investigator to understand any specific requirements.

What data supports the effectiveness of the drug NNC0487-0111 for obesity?

The research highlights that losing even 5% of body weight can lead to significant health improvements, and this is a common target for new obesity drugs. While specific data on NNC0487-0111 is not provided, the general effectiveness of weight loss drugs in achieving clinically meaningful weight loss is supported by the literature. ^{1 2 3 4 5}

What makes the drug NNC0487-0111 unique for treating obesity?

The drug NNC0487-0111 is unique because it may involve a novel mechanism of action or combination of ingredients not found in existing obesity treatments, potentially offering greater effectiveness or safety compared to current options like phentermine, sibutramine, and orlistat, which have limited weight loss effects and side effects. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults aged 18-55 with a BMI of 25.0 to 39.9 kg/m^2, who are in good health based on medical history, physical exams, and lab tests. It's not for those with certain blood or enzyme abnormalities or other conditions that could risk safety or protocol adherence.

Inclusion Criteria

Part C and D:

Considered eligible based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Body mass index (BMI) of 25.0 to 34.9 kilogram per square meter (kg/m^2) (both inclusive) at screening

Exclusion Criteria

HbA1c greater than or equal to 6.5 % (48 millimoles per mole (mmol/mol)) at screening

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

HbA1c greater than or equal to 6.5 % (48 mmol/mol) at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Single Ascending Dose (SAD)

Participants receive a single dose of NNC0487-0111 A or placebo with dose escalation between cohorts

22 days

Multiple visits for dosing and safety evaluation

Part B: Multiple Ascending Dose (MAD)

Participants receive NNC0487-0111 A or placebo once daily for 10 days with dose escalation between cohorts

31 days

Multiple visits for dosing and safety evaluation

Part C and D: Extended Treatment

Participants receive NNC0487-0111 A or B or placebo once daily for 12 weeks with dose escalation

12 weeks

Regular visits for dosing and safety evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

Treatment Details

Interventions

• NNC0487-0111 A
• NNC0487-0111 B
• Placebo A (NNC0487-0111 A)
• Placebo B (NNC0487-0111 B)

Trial Overview The study is testing NNC0487-0111, a new medication mimicking hormones amylin and GLP-1 to help reduce body weight by making people feel full. Participants will receive either the drug or placebo in various dosages over single doses up to a daily dose for 12 weeks.

Participant Groups

Group I: Part D Experimental Treatment 2 Interventions

Participants will receive NNC0487-0111 B or matching placebo once-daily for 12 weeks: 3 or 6 mg for weeks 1-2, 6 or 12 mg for weeks 3-4, 12 or 25 mg for weeks 5-6, 25 or 50 mg for weeks 7-8, 25 or 50 mg for weeks 9-10 and 50 or 2\*50 mg for weeks 11-12.

Group II: Part C Experimental Treatment 2 Interventions

Participants will receive NNC0487-0111 A or matching placebo once-daily for 12 weeks: 3 or 6 mg for weeks 1-2, 6 or 12 mg for weeks 3-4, 12 or 25 mg for weeks 5-6, 25 or 50 mg for weeks 7-8, 25 or 50 mg for weeks 9-10 and 50 or 2\*50 mg for weeks 11-12.

Group III: Part B: Multiple ascending dose (MAD) Experimental Treatment 2 Interventions

Participants will receive NNC0487-0111 once daily for 10 days at any of the five different dose levels (3, 6, 12, 25 and 50 milligrams (mg)) of NNC0487-0111 A or matching placebo in a sequential manner with the dose increasing between cohorts.

Group IV: Part A: Single ascending dose (SAD) Experimental Treatment 2 Interventions

Participants will receive a single dose of any of the six different dose levels (1, 3, 6, 12, 25 and 50 milligrams (mg)) of NNC0487-0111 A or matching placebo in a sequential manner with the dose increasing between cohorts.

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

Mild to moderate obesity affects public health more significantly than severe obesity, indicating a need for effective management strategies targeting this larger population.

An individualized approach to obesity treatment, along with advancements in pharmacologic therapies, may offer better outcomes compared to traditional lifestyle and behavioral modifications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical therapy for obesity. Dayyeh, BK., Kaplan, LM.[2011]

Successful treatment of obesity should not only focus on weight loss but also consider other measures like body mass index, body fat percentage, and improvements in obesity-related health complications such as diabetes and hypertension.

As obesity is a chronic disease, maintaining weight loss is crucial, and treatment success should be defined with varying criteria for minimal, intermediate, and full success based on individual responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposed standards for judging the success of the treatment of obesity. Atkinson, RL.[2019]

In a study of 598 patients with grade III obesity who underwent Roux-en-Y gastric bypass, an average weight loss of 45.5 kg (33.5%) was achieved within the first year post-surgery.

The surgery significantly improved obesity-related comorbidities, with reductions in serum glucose, total cholesterol, and LDL cholesterol, as well as a decreased prevalence of diabetes and dyslipidemia, indicating its efficacy in long-term health improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

WEIGHT LOSS AND METABOLIC OUTCOMES 12 MONTHS AFTER ROUX-EN-Y GASTRIC BYPASS IN A POPULATION OF SOUTHEASTERN BRAZIL. Pinhel, MA., Nicoletti, CF., de Oliveira, BA., et al.[2017]

Losing just 5% of body weight can lead to significant health improvements, but many individuals struggle to maintain weight loss through diet and exercise alone, highlighting the need for additional treatment options.

As of 2012, two new medications, lorcaserin and phentermine/topiramate, have been approved for long-term obesity treatment, and bariatric surgery is recommended for patients with severe obesity (BMI ≥40 or ≥35 with comorbidities) as a more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. Kushner, RF., Apovian, CM., Fujioka, K.[2018]

Weight loss of at least 5% can lead to significant improvements in health outcomes for individuals with obesity, including reductions in cardiometabolic risk factors, and is a key target for the approval of new anti-obesity medications.

For certain obesity-related conditions, such as type 2 diabetes and non-alcoholic steatohepatitis, greater weight loss (≥10% or ≥15%) may be necessary to achieve meaningful health improvements, highlighting the need for personalized weight loss goals based on individual health profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is clinically relevant weight loss for your patients and how can it be achieved? A narrative review. Horn, DB., Almandoz, JP., Look, M.[2022]

Pharmacologic treatments for obesity, such as phentermine, sibutramine, and orlistat, typically lead to an additional weight loss of about 2-5 kg compared to placebo, but there is a need for more effective and safer options.

Several new antiobesity drugs are in late-stage development, targeting various mechanisms like appetite suppression and nutrient absorption, which may enhance treatment options for obesity in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs in the pipeline for the obesity market. Klonoff, DC., Greenway, F.[2021]

Sibutramine and orlistat are the only two anti-obesity medications approved for long-term use, with sibutramine reducing food intake and orlistat inhibiting fat absorption, though orlistat can cause gastrointestinal side effects like flatulence and diarrhea.

Rimonabant, an endocannabinoid receptor antagonist approved in 2006, was suspended in 2008 due to psychiatric side effects, highlighting the need for further studies on the long-term safety and efficacy of anti-obesity medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for obesity. Li, M., Cheung, BM.[2021]

The conference highlighted various innovative approaches to developing safe and effective obesity drugs, focusing on different neuroendocrine and peripheral tissue targets, which is crucial given the global obesity epidemic.

Key agents discussed included rimonabant, which has completed extensive phase III trials, and early-stage drugs like selective 5-HT(2C) agonists and synthetic analogs of gut hormones, indicating a diverse pipeline of potential treatments for obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity Drug Development Summit. 21-22 July, 2005, Arlington, VA, USA. Maggio, CA.[2007]

References

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

Medical therapy for obesity. [2011]

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

Proposed standards for judging the success of the treatment of obesity. [2019]

3. Spain pubmed.ncbi.nlm.nih.gov

WEIGHT LOSS AND METABOLIC OUTCOMES 12 MONTHS AFTER ROUX-EN-Y GASTRIC BYPASS IN A POPULATION OF SOUTHEASTERN BRAZIL. [2017]

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

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. [2018]

5. England pubmed.ncbi.nlm.nih.gov

What is clinically relevant weight loss for your patients and how can it be achieved? A narrative review. [2022]

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

Drugs in the pipeline for the obesity market. [2021]

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

Pharmacotherapy for obesity. [2021]

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

Milestones in the journey towards addressing obesity; Past trials and triumphs, recent breakthroughs, and an exciting future in the era of emerging effective medical therapies and integration of effective medical therapies with metabolic surgery. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for obesity. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Obesity Drug Development Summit. 21-22 July, 2005, Arlington, VA, USA. [2007]