A Research Study on How NNC0487-0111 Works in People With Overweight or Obesity

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.

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.

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.

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.

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.

Part A: From pre-dose on Day 1 to 22 days; Part B: From pre-dose on Day 1 to 31 days; Part C and D: From pre-dose on Day 1 to 105 days

Part A: AUC0-∞,SD; the area under the NNC0487-0111 plasma concentration-time curve from time 0 to infinity after a single dose

Part B: AUC0-24h,MD; the area under the NNC0487-011 plasma concentration-time curve from time 0 to 24 hours after last multiple dose

Part C and D: AUC0-24h,MD; the area under the NNC0487-011 plasma concentration-time curve from time 0 to 24 hours after last multiple 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