History of Changes for Study: NCT05363774

Version	Submitted Date	Changes
1	May 5, 2022	None (earliest Version on record)
2	July 25, 2022	Study Status and Arms and Interventions
3	September 9, 2022	Study Status
4	November 11, 2022	Study Status and Contacts/Locations
5	December 27, 2022	Outcome Measures, Arms and Interventions, Study Status, Eligibility and Study Description
6	July 16, 2023	Outcome Measures, Arms and Interventions, Study Status, Eligibility and Study Description
7	October 31, 2023	Study Status
8	April 30, 2024	Recruitment Status, Study Status, Contacts/Locations and Study Design

Brief Summary:

NNC0519-0130 is a study medicine with the potential to improve metabolism of fat and sugar and fat in the body of patients with diabetes and to lower the body weight in people who are overweight. The safety and tolerability of the new medicine NNC0519-0130 and its concentrations in the blood will be looked for in this study. Moreover, effects on blood sugar, fat metabolism and body weight will be tested. There will be different study parts with different participants. Healthy participants (men) with high body weight and people with diabetes (men and women) will take part. Single doses and multiple doses will be tested and the medicine will be studied as an injection or will be given orally (as a tablet). The treatment participants get is decided by chance. Single ascending dose (SAD) part: In the first part of the study; the effects of single injected doses of NNC0519-0130 will be examined. Participants will either get one dose of the new medicine NC0519-0130 or one dose of placebo that does not contain active medicine. The injection will be given by trained staff into the tissue underneath the skin of belly. The study will last between 3 ½ weeks up to a approximately 7 weeks (up to 11 weeks in case of rescheduling). Participants will have 9 visits with the study doctor, including one 6-day inhouse stay (5 nights). Multiple ascending dose (MAD) subcutaneous part: In this part of the study; the effects of daily injected doses of NNC0519-0130 taken over the course of several weeks will be examined. Participants will take the study medicine once daily and that the dose is increased every three weeks, if safety and tolerability allow. Participants will take up to five different dose levels. The period with daily injections of study medicine will in total last up to 15 weeks. Participants will either get the study medicine NNC0519-0130 or placebo (a 'dummy' medicine that looks like the medicines but without any active medicine). Participants will have up to six in-house stays (of 4 to 7 days each), and up to 15 outpatient visits and up to 35 telephone visits. The total duration of the study could last up to 27 weeks. MAD Oral part: In this part of the study; the effects of daily oral doses of NNC0519-0130 taken as tablets over the course of several weeks will be examined. Participants take the study medicine once daily and that the dose is increased every three weeks, if safety and tolerability allow. Participants will take up to four different dose levels. Total period with daily intake of the study medicine will last 12 weeks. Participants will either get the study medicine NNC0519-0130 or placebo (a 'dummy' medicine that looks like the medicines but without any active medicine). Participants will have up to 5 in-house stays (4 to 5 days each), and up to13 outpatient visits and up to 28 telephone visits. The total duration of the study could last up to 24 weeks. Type 2 diabetes (T2D) part: In this part of the study; the effects in patients with type 2 diabetes who take once daily injected doses of NNC0519-0130 over a course of 4 weeks will be examined. Treatment starts with a relatively low dose which is increased after 1 week and 2 weeks of treatment and the target dose will then be taken during the last 2 weeks of treatment. Participants will either be treated with the study medicine NNC0519-0130 or with placebo (a 'dummy' medicine that looks like the medicines but without any active medicine). Participants will have 4 in-house stays (4 to 5 days each), 6 outpatient visits and 12 telephone visits. The total duration of the study could last up to 16 weeks.

Detailed Description:

Arms and Interventions

Arms	Assigned Interventions
Experimental: Single ascending dose (SAD) part Participants will receive up to six dose levels of subcutaneous NNC0519-0130 or matching placebo in a sequential manner with the dose increasing between cohorts.	Drug: NNC0480-0389 SAD part: Participants will receive up to six dose levels of subcutaneous NNC0519-0130 in a sequential manner with the dose increasing between cohorts. MAD part: The participants in first cohort will receive NNC0519-0130 subcutaneously up to 5 dose levels, and the participants in the second MAD cohort will receive NNC0519-0130 orally up to 4 dose levels. T2D part: Participants will receive NNC0519-0130 up to three dose levels with dose escalation within the cohort. Drug: Placebo (NNC0480-0389) SAD part: Participants will receive up to six dose levels of subcutaneous placebo (NNC0519-0130) in a sequential manner with the dose increasing between cohorts. MAD part: Participants in first cohort will receive placebo (NNC0519-0130) subcutaneously up to 5 dose levels, and the participants in the second MAD cohort will receive NNC0519-0130 orally up to 4 dose levels. T2D part: Participants will receive placebo (NNC0519-0130) up to three dose levels with dose escalation within the cohort.
Experimental: Multiple ascending dose (MAD) part MAD part comprises two cohorts in participants with overweight or obesity and a cohort in participants with type 2 diabetes (T2D). The participants in first cohort will receive NNC0519-0130 or matching placebo subcutaneously up to 5 dose levels, and the participants in the second MAD cohort will receive NNC0519-0130 or matching placebo orally up to 4 dose levels.	Drug: NNC0480-0389 SAD part: Participants will receive up to six dose levels of subcutaneous NNC0519-0130 in a sequential manner with the dose increasing between cohorts. MAD part: The participants in first cohort will receive NNC0519-0130 subcutaneously up to 5 dose levels, and the participants in the second MAD cohort will receive NNC0519-0130 orally up to 4 dose levels. T2D part: Participants will receive NNC0519-0130 up to three dose levels with dose escalation within the cohort. Drug: Placebo (NNC0480-0389) SAD part: Participants will receive up to six dose levels of subcutaneous placebo (NNC0519-0130) in a sequential manner with the dose increasing between cohorts. MAD part: Participants in first cohort will receive placebo (NNC0519-0130) subcutaneously up to 5 dose levels, and the participants in the second MAD cohort will receive NNC0519-0130 orally up to 4 dose levels. T2D part: Participants will receive placebo (NNC0519-0130) up to three dose levels with dose escalation within the cohort.
Experimental: Type 2 diabetes (T2D) part Participants will receive NNC0519-0130 or matching placebo up to three dose levels with dose escalation within the cohort.	Drug: NNC0480-0389 SAD part: Participants will receive up to six dose levels of subcutaneous NNC0519-0130 in a sequential manner with the dose increasing between cohorts. MAD part: The participants in first cohort will receive NNC0519-0130 subcutaneously up to 5 dose levels, and the participants in the second MAD cohort will receive NNC0519-0130 orally up to 4 dose levels. T2D part: Participants will receive NNC0519-0130 up to three dose levels with dose escalation within the cohort. Drug: Placebo (NNC0480-0389) SAD part: Participants will receive up to six dose levels of subcutaneous placebo (NNC0519-0130) in a sequential manner with the dose increasing between cohorts. MAD part: Participants in first cohort will receive placebo (NNC0519-0130) subcutaneously up to 5 dose levels, and the participants in the second MAD cohort will receive NNC0519-0130 orally up to 4 dose levels. T2D part: Participants will receive placebo (NNC0519-0130) up to three dose levels with dose escalation within the cohort.

Primary Outcome Measures:

Number of treatment emergent adverse events (TEAE) in single ascending dose (SAD) part
[ Time Frame: From time of dosing (day 1) until completion of the follow-up visit (assessed up to 22 days) ]

Measured as Number of events

Number of treatment emergent adverse events (TEAE) in Multiple ascending dose (MAD) part for the subcutaneous cohort
[ Time Frame: From time of dosing (day 1) until completion of the follow-up visit (assessed up to 133 days) ]

Measured as Number of events

Number of treatment emergent adverse events (TEAE) in Type 2 diabetes (T2D) part
[ Time Frame: From time of first dosing (day 1) until completion of the follow-up visit (assessed up to 56 days) ]

Measured as Number of events

Secondary Outcome Measures:

AUC0-∞,NNC0519-0130,SD: Area under the NNC0519-0130 plasma concentration-time curve from time 0 (time of dosing) to infinity after a single dose
[ Time Frame: From pre-dose (day 1) until completion of the follow-up visit (assessed up to 22 days) ]

Measured in h*nmol/L

Cmax,NNC0519-0130,SD: Maximum plasma concentration of NNC0519-0130 after a single dose
[ Time Frame: From pre-dose (day 1) until completion of the follow-up visit (assessed up to 22 days) ]

Measure in nmol/L

Number of treatment emergent adverse events (TEAE) in Multiple ascending dose (MAD) part for the oral cohort
[ Time Frame: From time of dosing (day 1) until completion of the follow-up visit (assessed up to 112 days) ]

Measured as Number of events

AUC0-24h,NNC0519-0130,MD: Area under the NNC0519-0130 plasma concentration-time curve after the last dose in each treatment period in Multiple ascending dose (MAD) part
[ Time Frame: From pre-dose (last dose in each treatment period) until 24 hours post-dose ]

Measured in h*nmol/L

Cmax,NNC0519-0130,MD: Maximum plasma concentration of NNC0519-0130 after the last dose in each treatment period in Multiple ascending dose (MAD) part
[ Time Frame: From pre-dose (last dose in each treatment period) until 24 hours postdose ]

Measured in nmol/L

AUC0-24h,NNC0519-0130,MD: Area under the NNC0519-0130 plasma concentration-time curve of the last dose in a treatment period in Type 2 diabetes (T2D) part
[ Time Frame: From pre-dose (last dose in each treatment period) until 24 hours post-dose ]

Measured in h*nmol/L

Cmax,NNC0519-0130,MD: Maximum plasma concentration of NNC0519-0130 after the last dose in a treatment period in T2D part
[ Time Frame: From pre-dose (last dose in each treatment period) until 24 hours post-dose ]

Measured in nmol/L

Minimum Age:

18 Years

Maximum Age:

64 Years

Sex:

All

Gender Based:

Accepts Healthy Volunteers:

Yes

Criteria:

Inclusion Criteria:

Single ascending dose (SAD) part:
Male aged 18-55 years (both inclusive) at screening
Body mass index between 18.5 kilogram per meter square (kg/m^2) and 27.0 kg/m^2 (both inclusive) at screening
Considered to be generally healthy 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
Multiple ascending dose (MAD) part:
Male aged 18-55 years (both inclusive) at screening
Body mass index between 25.0 kg/m^2 and 39.9 kg/m^2 (both inclusive) at screening. Overweight should be due to excess adipose tissue, as judged by the investigator
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
Type 2 diabetes (T2D) part:
Female of non-childbearing potential or male aged 18-64 years (both inclusive) at screening
Body mass index between 25.0 kg/m^2 and 39.9 kg/m^2 (both inclusive) at screening
Diagnosed with type 2 diabetes mellitus greater than or equal to (≥) 180 days before screening
Treatment naive to antidiabetic drugs or on a stable daily dose(s) metformin therapy (any metformin formulation) within 90 days before screening. The metformin dose should be greater than or equal to (≥) 1000 milligrams (mg) to less than or equal to (≤) 3000 mg or maximum tolerated or effective dose documented in participant's medical record or per investigator discretion
Insulin naive. However, short-term insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes
HbA1c in the range of 6.5% (inclusive) and 9.5% (inclusive)

Exclusion Criteria:

Single ascending dose (SAD) part:
Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol
Glycosylated haemoglobin (HbA1c) greater than or equal to (≥) 6.5 % (48 millimoles per mole (mmol/mol)) at screening
Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of paracetamol, ibuprofen, acetylsalicylic acid, and domperidon, or topical medication not reaching systemic circulation, within 14 days before screening
Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol
Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions
HbA1c greater than or equal to (≥) 6.5 % (48 mmol/mol) at screening
Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of paracetamol, ibuprofen, acetylsalicylic acid, and domperidon, or topical medication not reaching systemic circulation, within 14 days before screening
Multiple ascending dose (MAD) part:
Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol
Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions
HbA1c greater than or equal to (≥) 6.5 % (48 mmol/mol) at screening
Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of paracetamol, ibuprofen, acetylsalicylic acid, and domperidon, or topical medication not reaching systemic circulation, within 14 days before screening
Type 2 diabetes (T2D) part:
Any disorder, except for conditions associated with T2D, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol
Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological conditions (except conditions associated with diabetes mellitus)
Current treatment with systemically effective corticosteroids, monoamine oxidase (MAO) inhibitors, systemic non-selective beta-blockers, growth hormone, non-routine vitamins or herbal products
Current treatment with selected oral medication with a narrow therapeutic window, such as warfarin, digoxin, tricyclic antidepressants, lithium, aminophylline, theophylline and anticonvulsants