Diabetes Mellitus
Conditions
Brief summary
The purpose of this clinical study is to find out how NNC0487-0111 affects, how the body uses insulin (a hormone that helps the body control blood sugar) and how well the pancreas works in people living with type 2 diabetes. There are 2 study treatments. Participants will get either NNC0487-0111 (the treatment being tested) or Placebo (a treatment that has no active medicine in it). Which treatment participants get is decided by chance.
Interventions
DRUGNNC0487-0111
NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.
DRUGPlacebo
Placebo matched to NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female. * Age 18-75 years (both inclusive) at the time of signing the informed consent. * Diagnosed with type 2 diabetes more than or equal to (≥)180 days before screening. * Only stable daily dose(s) of metformin at effective or maximum tolerated dose, as judged by the investigator for at least 90 days before screening. If additional oral antidiabetic drug (OAD) is required, only stable dose(s) of sodium-glucose cotransporter-2 inhibitors (SGLT2i) is permitted, and this must also have been maintained for at least 90 days before screening. * HbA1c at screening of 6.5-9.5% \[48-80 millimole per mole (mmol/mol)\] (both inclusive) if on metformin only, or 6.0-9.0% (42-75 mmol/mol) (both inclusive) if on metformin in combination with SGLT2i.
Exclusion criteria
* Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method. * Presence of type 1 diabetes. * Any clinically significant body weight change (≥5% self-reported change) or dieting attempts (e.g., participation in a weight reduction program) within 90 days before screening. * Treatment with any medication for the indication of T2D or weight management other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed. * Treatment with a GLP-1 receptor agonist. * Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) before screening or are expected to require treatment after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination. * Presence or history of cardiovascular disease including stable and unstable angina pectoris, myocardial infarction, transient ischaemic attack, stroke, cardiac decompensation, clinically significant arrhythmias or clinically significant conduction disorders within 180 days before screening. * Renal impairment with estimated glomerular filtration rate (eGFR) less than (\<) 60.0 milliliter per minute per meter square (ml/min/1.73 m\^2) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in M-value in Hyperinsulinaemic euglycaemic clamp (HEC) | Baseline to week 40 | Measured as milligram per minute per kilogram (mg/min/kg) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in M-value in HEC, normalised by lean body mass | Baseline to week 40 | Measured as mg/min/kg |
| Change in first-phase incremental Insulin Secretion Rate (ISR0-8 min) in Hyperglycaemic clamp (HGC) | Baseline to week 40 | Measured as picomole per minute per meter square (pmol/min/m\^2) |
| Change in second-phase ISR (ISR20-120 min) in HGC | Baseline to week 40 | Measured as pmol/min/m\^2 |
| Change in total ISR (ISR0-120 min) in HGC | Baseline to week 40 | Measured as pmol/min/m\^2 |
| Change in ISR at fixed glucose concentration (ISRg) in HGC | Baseline to week 40 | Measured as pmol/min/m\^2 |
| Change in total insulin response [total area under curve (AUC0-120) min] in HGC | Baseline to week 40 | Measured as picomole per liter per minute (min\*pmol/L) |
| Change in clamp disposition index (cDI) calculated from HEC and HGC | Baseline to week 40 | Measured as picomole per liter per meter square per minute square per kilogram (pmol\*L/m\^2/min\^2/kg) |
| Change in cDI calculated from HEC and HGC, based on lean body mass | Baseline to week 40 | Measured as pmol\*L/m\^2/min\^2/kg |
| Change in β-cell glucose sensitivity (insulin secretion) from HGC | Baseline to week 40 | Measured as picomole per minute per meter square per millimoles per liter \[pmol/min/m\^2/ (mmol/L)\] |
| Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose) | Baseline to week 40 | Measured as pmol/min/m\^2/ (mmol/L) |
| Change in glycated haemoglobin (HbA1c) | Baseline to week 40 | Measured as percentage (%) of HbA1c |
Countries
Germany
Contacts
CONTACTNovo Nordisk
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Outcome results
None listed