Diabetes Mellitus, Type 2Phase 1NCT03945656
A Research Study of How Overdosing of a New Once Weekly Medicine NNC0148-0287 C (Insulin 287) Influences the Blood Sugar Level in People With Type 2 Diabetes
A Phase 1 study testing insulin icodec and Insulin glargine in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 1 site in Austria.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- insulin icodec and Insulin glargine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteAustria
- Study dates
- 7 May 2019to 27 Sep 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Trial Investigating the Hypoglycaemic Response to Overdosing of NNC0148-0287 C (Insulin 287) in Subjects With Type 2 Diabetes
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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- insulin icodec, Insulin glargine
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
insulin icodecDrug
Also called Insulin 287
Participants will receive subcutaneous (s.c.) injections of insulin 287 OW for 6 weeks
Insulin glargineDrug
Participants will receive daily s.c. injections of insulin glargine U100 for 12 days
| Study group | Role | What they receive |
|---|---|---|
| Insulin 287 followed by insulin glargine | Experimental | Run-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment.
After run-in, participants will receive insulin 287 once a week (OW) for 6 weeks.
After insulin 287 treatment, participants will receive insulin glargine U100 OD for 12 days. Receives: Drug: insulin icodec; Drug: Insulin glargine |
| Insulin glargine followed by insulin 287 | Active comparator | Run-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment.
After run-in, participants will receive insulin glargine U100 OD for 12 days.
After insulin glargine treatment, participants will receive insulin 287 OW for 6 weeks. Receives: Drug: insulin icodec; Drug: Insulin glargine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: 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
Secondary outcomes (21)
PG (nadir) - PG concentration at nadir after 2 and 3 times the individualised optimal basal dose of insulin
Measured in mmol/L
Minimum blood sugar level achieved after receiving a double or triple dose of basal insulin
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
C (glucagon, PG nadir) - Plasma glucagon concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
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
Measured: 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
C (adrenaline, PG nadir) - Plasma adrenaline concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
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
Measured: 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
C (noradrenaline, PG nadir) - Plasma noradrenaline concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
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
Measured: 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
C (growth hormone [GH], PG nadir) - Serum growth hormone concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
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
Measured: 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
C (cortisol, PG nadir) - Serum cortisol concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
Hypoglycaemia awareness (HA) (PG nadir) - HA at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
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
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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2019
- Study start7 May 2019
- Primary completion27 Sep 2021
- Study completion27 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Reporting Anchor and Disclosure (1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03945656
- Sponsor's protocol ID
- NN1436-4462
- Other IDs
- U1111-1214-2688, 2018-001993-74, 2018
- Status last verified
- Aug 2023
- First submitted
- 8 May 2019
- Last updated
- 6 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
Pieber TR, Arfelt KN, Cailleteau R, Hart M, Kar S, Mursic I, Svehlikova E, Urschitz M, Haahr H. Hypoglycaemia frequency and physiological response after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100 in type 2 diabetes: a randomised crossover trial. Diabetologia. 2023 Aug;66(8):1413-1430. doi: 10.1007/s00125-023-05921-8. Epub 2023 Jun 13.
PubMed 37308751
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial Investigating the Hypoglycaemic Response to Overdosing of NNC0148-0287 C (Insulin 287) in Subjects With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT03945656
- Acronym / sponsor ID
- NN1436-4462
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 7 May 2019 (actual)
- Primary completion
- 27 Sep 2021 (actual)
- Study completion
- 27 Sep 2021 (actual)
- First posted
- 10 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin 287 followed by insulin glargine | Experimental | Drug: insulin icodec, Drug: Insulin glargineRun-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment. After run-in, participants will receive insulin 287 once a week (OW) for 6 weeks. After insulin 287 treatment, participants will receive insulin glargine U100 OD for 12 days. |
| Insulin glargine followed by insulin 287 | Active comparator | Drug: insulin icodec, Drug: Insulin glargineRun-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment. After run-in, participants will receive insulin glargine U100 OD for 12 days. After insulin glargine treatment, participants will receive insulin 287 OW for 6 weeks. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| insulin icodecAlso: Insulin 287Participants will receive subcutaneous (s.c.) injections of insulin 287 OW for 6 weeks | Drug | Insulin 287 followed by insulin glargine, Insulin glargine followed by insulin 287 |
| Insulin glargineParticipants will receive daily s.c. injections of insulin glargine U100 for 12 days | Drug | Insulin 287 followed by insulin glargine, Insulin glargine followed by insulin 287 |
Primary outcome
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
Time frame: 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
21 secondary outcomes
PG (nadir) - PG concentration at nadir after 2 and 3 times the individualised optimal basal dose of insulin
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
C (glucagon, PG nadir) - Plasma glucagon concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
Time frame: 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
C (adrenaline, PG nadir) - Plasma adrenaline concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
Time frame: 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
C (noradrenaline, PG nadir) - Plasma noradrenaline concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
Time frame: 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
C (growth hormone [GH], PG nadir) - Serum growth hormone concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
Time frame: 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
C (cortisol, PG nadir) - Serum cortisol concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
Hypoglycaemia awareness (HA) (PG nadir) - HA at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin
Time frame: 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
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
Time frame: 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
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
Time frame: 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
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
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2023.
- Background: PubMed 37308751Pieber TR, Arfelt KN, Cailleteau R, Hart M, Kar S, Mursic I, Svehlikova E, Urschitz M, Haahr H. Hypoglycaemia frequency and physiological response after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100 in type 2 diabetes: a randomised crossover trial. Diabetologia. 2023 Aug;66(8):1413-1430. doi: 10.1007/s00125-023-05921-8. Epub 2023 Jun 13.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Related trials for Diabetes Mellitus, Type 2
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Reporting Anchor and Disclosure (1452) study director
Novo Nordisk A/S
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing insulin icodec and Insulin glargine in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03945656, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2023.