NNC0487-0111 is a new medicine similar to 2 hormones that are produced in human body: amylin and glucagon-like peptide-1 (GLP-1). Both hormones work like body's own hormones and help the body to feel full. This study tests if the study medicine is safe and to find out how the medicine works in humans. 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 study will have 4 parts: Part A, B, C and D. Part A: This is planned to consist of five groups, one additional group may be added. Each group will include 8 participants, with 6 participants being randomised to receive a single dose of NNC0487-0111 A and 2 participants randomised to receive placebo. The dosing within each group will be sequential, i.e., 2 sentinel participants (1 on active and 1 on placebo).

Part B: This is planned to consist of three groups, one additional group may be added. Each group will include 12 participants, with 9 participants being randomised to receive NNC0487-0111 A and 3 participants randomised to receive placebo once daily for 10 days. The dosing within each group will be sequential. For the first group, 4 sentinel participants (3 on active and 1 on placebo) will be dosed followed by a safety observation period of 7 days (168 hours), before dosing of the remaining participants in the group will be initiated. For the remaining groups, 4 sentinel participants (3 on active and 1 on placebo) will be dosed followed by a safety observation period of at least 36 hours before dosing of the remaining participants in the group will be initiated.

Part C and D are matching regarding planned visits and procedures, but the study interventions in Part D (NNC0487-0111 B) differ from Part A, B and C (NNC0487-0111 A). Each part is planned to consist of one group, although one additional group may be added. Each group will include 20 participants, with 16 participants being randomised to receive active treatment and 4 participants randomised to receive placebo once-daily for 12 weeks. The dosing will be sequential, i.e., 4 sentinel participants (3 on active and 1 on placebo) will be dosed followed by a safety observation period of at least 36 hours before dosing of the remaining participants in the cohort will be initiated. The remaining participants will be dosed in smaller groups of 8 participants separated by a safety observation period of at least 36 hours.

A safety evaluation will be made between dosing of participants within a group and before moving on to a higher dose.

Inclusion Criteria:

Part A and B:

• Male or female aged 18-55 years (both inclusive) at time of signing informed consent
• Body mass index (BMI) of 25.0 to 34.9 kilogram per square meter (kg/m^2) (both inclusive) at screening
• 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.

Part C and D:

• Male or female aged 18-55 years (both inclusive) at time of signing informed consent
• Body mass index (BMI) of 27.0 to 39.9 kg/m^2 (both inclusive) at screening
• 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.

Exclusion Criteria:

Part A and B:

• 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 millimoles per mole (mmol/mol)) at screening
• Any laboratory safety parameters at screening outside the below laboratory ranges, see designated reference range documents for specific values
• Vitamin D (25-hydroxycholecalciferol) less than 20 Nanograms per milliliter (ng/mL) (50 nano molar (NM)) at screening
• Parathyroid hormone (PTH) outside normal range at screening
• Total calcium outside normal range at screening
• Amylase greater than or equal to 2 times upper limit of normal at screening
• Lipase greater than or equal to 2 times upper limit of normal at screening

Part C and D:

• 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
• Any laboratory safety parameters at screening outside the below laboratory ranges, see designated reference range documents for specific values:
• Vitamin D (25-hydroxycholecalciferol) less than 20 ng/mL (50 nM) at screening
• Parathyroid hormone (PTH) outside normal range at screening
• Total calcium outside normal range at screening
• Amylase greater than or equal to 2 times upper limit of normal at screening
• Lipase greater than or equal to 2 times upper limit of normal at screening

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Sponsor staff involved in the clinical trial is masked according to company standard procedures.