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

Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT03945656
Collaborator
(none)
43
Enrollment
1
Location
2
Arms
28.7
Actual Duration (Months)
1.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is comparing the effect of a long-acting insulin analogue (insulin 287) with insulin glargine (LantusĀ®) 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.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: insulin icodec
  • Drug: Insulin glargine
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
43 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Trial Investigating the Hypoglycaemic Response to Overdosing of NNC0148-0287 C (Insulin 287) in Subjects With Type 2 Diabetes
Actual Study Start Date :
May 7, 2019
Actual Primary Completion Date :
Sep 27, 2021
Actual Study Completion Date :
Sep 27, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Insulin 287 followed by insulin glargine

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.

Drug: insulin icodec
Participants will receive subcutaneous (s.c.) injections of insulin 287 OW for 6 weeks
Other Names:
  • Insulin 287
  • Drug: Insulin glargine
    Participants will receive daily s.c. injections of insulin glargine U100 for 12 days

    Active Comparator: Insulin glargine followed by insulin 287

    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.

    Drug: insulin icodec
    Participants will receive subcutaneous (s.c.) injections of insulin 287 OW for 6 weeks
    Other Names:
  • Insulin 287
  • Drug: Insulin glargine
    Participants will receive daily s.c. injections of insulin glargine U100 for 12 days

    Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. 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

    7. 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

    8. 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

    9. 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

    10. 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

    11. 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

    12. 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

    13. 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

    14. 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

    15. 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

    16. 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

    17. 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

    18. 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

    19. 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

    20. 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

    21. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 72 Years
    Sexes Eligible for Study:
    All
    Accepts 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).

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Novo Nordisk Investigational SiteGrazAustria8010

    Sponsors and Collaborators

    • Novo Nordisk A/S

    Investigators

    • Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novo Nordisk A/S
    ClinicalTrials.gov Identifier:
    NCT03945656
    Other Study ID Numbers:
    • NN1436-4462
    • U1111-1214-2688
    • 2018-001993-74
    First Posted:
    May 10, 2019
    Last Update Posted:
    Oct 7, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 7, 2021