Diabetes Mellitus, Type 2
Conditions
Brief summary
This study is comparing the effect of a long-acting insulin analogue (insulin 287) with insulin glargine (Lantus®) in subjects with type 2 diabetes. In addition, the study is looking at symptoms of low blood sugar, awareness of low blood sugar and the time and amount of glucose needed to recover from low blood sugar after injecting 2 and 3 times the basal dose of insulin 287 and glargine. The purpose of the study is to make a once-weekly injectable basal insulin treatment for people with type 2 diabetes. Participants will get insulin 287 as well as insulin glargine - which treatment any participant gets first is decided by chance. Insulin 287 is a new medicine; insulin glargine can already be prescribed. The study medicines will be in a pen, and must be injected with a needle in the thigh once per day (insulin glargine) or once per week (insulin 287). The study will last for minimum 3 months and up to approximately 6 months. Participants will have 21 clinic visits and at least 2 phone calls with the study doctor. The participants' health will be monitored carefully and blood samples will be taken at the clinic visits.
Interventions
DRUGinsulin icodec
Participants will receive subcutaneous (s.c.) injections of insulin 287 OW for 6 weeks
DRUGInsulin glargine
Participants will receive daily s.c. injections of insulin glargine U100 for 12 days
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 72 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, aged between 18 and 72 years (both inclusive) at the time of signing informed consent. * Body mass index between 18.5 and 37.9 kg/m\^2 (both inclusive). * Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening. * Glycosylated haemoglobin type A1c (HbA1c) less than or equal to 9.0% (less than or equal to 74 mmol/mol) at screening. * Current total daily insulin treatment between 0.2 and 1.0 U/kg/day (both inclusive).
Exclusion criteria
* Known or suspected hypersensitivity to trial products or related products. * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method. * Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological conditions (except conditions associated with diabetes mellitus).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically significant hypoglycaemia (Double dose): Clinically significant hypoglycaemia (Plasma glucose [PG] less than 3.0 mmol/L [54 mg/dL]) after 2 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 times the individualised optimal basal dose of insulin (day 17 for insulin 287, day 4 for insulin glargine) until termination of the clamp the following day | Yes/No Blood sugar lower than 3.0 mmol/L (54 mg/dL) after receiving a double dose of basal insulin Number of subjects experiencing an event is to be reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| t (decline, PG 5.5 mmol/L - PG 3.0 mmol/L) - Time from start of hypoglycaemia induction until a PG concentration of 3.0 mmol/L (54 mg/dL) is reached after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in hours Time from when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until blood sugar is 3.0 mmol/L (54 mg/dL) after receiving a double or triple dose of basal insulin |
| t (decline, PG 5.5 mmol/L - PG nadir) - Time from start of hypoglycaemia induction until PGnadir is reached after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in hours Time from when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| t (recovery, PG nadir - PG 5.5 mmol/L) - Time to increase from PGnadir to a PG concentration of 5.5 mmol/L (100 mg/dL) after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in hours Time from when blood sugar is at a minimum level until blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] during recovery from low blood sugar after receiving a double or triple dose of basal insulin |
| C (glucagon, PG nadir) - Plasma glucagon concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in pg/mL Blood level of the glucagon hormone at the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| C (adrenaline, PG nadir) - Plasma adrenaline concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in pg/mL Blood level of the adrenaline hormone at the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| C (noradrenaline, PG nadir) - Plasma noradrenaline concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in pg/mL Blood level of the noradrenaline hormone at the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| C (growth hormone [GH], PG nadir) - Serum growth hormone concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in ng/mL Blood level of GH at the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| C (cortisol, PG nadir) - Serum cortisol concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in ng/mL Blood level of the cortisol hormone at the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| Pulse (PG 5.5 mmol/L - PG nadir) - Change in pulse rate from a PG concentration of 5.5 mmol/L (100 mg/dL) until PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in beats/min Change in pulse from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| Diastolic blood pressure (DBP) (PG 5.5 mmol/L - PG nadir) - Change in diastolic blood pressure from a PG concentration of 5.5 mmol/L (100 mg/dL) until PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in mmHg Change in DBP from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| PG (nadir) - PG concentration at nadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in mmol/L Minimum blood sugar level achieved after receiving a double or triple dose of basal insulin |
| Digit Symbol Substitution Test (DSST) (PG 5.5 mmol/L - PG nadir) - Change in DSST score from a PG concentration of 5.5 mmol/L (100 mg/dL) until PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Number of correct responses Change in performance in the DSST (a cognitive ability test) from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| Four-Choice Reaction Time (4CRT) (reaction 4CRT) (PG 5.5 mmol/L - PG nadir) - Change in 4CRT performance from a PG concentration of 5.5 mmol/L (100 mg/dL) until PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in msec Change in reaction time in the 4CRT test (a cognitive ability test) from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| 4CRT (% correct answers) (PG 5.5 mmol/L - PG nadir) - Change in 4CRT performance (% correct answers) from a PG concentration of 5.5 mmol/L (100 mg/dL) until PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in %-points Change in the percentage correct answers in the 4CRT test (a cognitive ability test) from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| Trail Making B test (TMB) (PG 5.5 mmol/L - PG nadir) - Change in TMB from a PG concentration of 5.5 mmol/L (100 mg/dL) until PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in sec Change in performance in the TMB (a cognitive ability test) from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| Hypoglycaemic symptoms score (HSS) (PG 5.5 mmol/L - PG nadir) - Change in HSS from a PG concentration of 5.5 mmol/L (100 mg/dL) to PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Test score (arbitrary units) Change in symptoms of low blood sugar from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| Hypoglycaemia awareness (HA) (PG nadir) - HA at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Yes/No Number of subjects with a feeling of low blood sugar at the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
| AUC (GIR, recovery, PG nadir -PG 5.5 mmol/L) - Area under the glucose infusion rate-time profile during recovery from PGnadir to a PG concentration of 5.5 mmol/L (100 mg/dL) after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in mg/kg Amount of glucose needed to be infused to increase blood sugar from a minimum level to a normal level \[5.5 mmol/L (100 mg/dL)\] during recovery from low blood sugar after receiving a double or triple dose of basal insulin |
| AUC (GIR, recovery, PG 5.5 mmol/L, 0-6h)-Area under the glucose infusion rate-time profile during 6 hours at a PG concentration of 5.5 mmol/L (100 mg/dL) after recovery from hypoglycaemia after 2 & 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in mg/kg Amount of glucose needed to be infused to keep blood sugar at a normal level \[5.5 mmol/L (100 mg/dL)\] for 6 hours after recovery from low blood sugar after receiving a double or triple dose of basal insulin |
| Clinically significant hypoglycaemia (Triple dose) - Clinically significant hypoglycaemia [PG less than 3.0 mmol/L (54 mg/dL)], after 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 3 times the individualised optimal basal dose of insulin (day 38 for insulin 287, day 11 for insulin glargine) until termination of the clamp the following day | Yes/No Blood sugar lower than 3.0 mmol/L (54 mg/dL) after receiving a triple dose of basal insulin Number of subjects experiencing an event is to be reported |
| Systolic blood pressure (SBP) (PG 5.5 mmol/L - PG nadir) - Change in systolic blood pressure from a PG concentration of 5.5 mmol/L (100 mg/dL) until PGnadir after 2 and 3 times the individualised optimal basal dose of insulin | From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day | Measured in mmHg Change in SBP from the time point when blood sugar is normal \[5.5 mmol/L (100 mg/dL)\] until the time point when blood sugar is at a minimum level after receiving a double or triple dose of basal insulin |
Countries
Austria
Outcome results
None listed