Clinical trial NCT03723772: A Research Study of How Different Doses of a New Medicine NNC0148-0287 C (Insulin 287) Work on the Blood Sugar in People With Type 1 Diabetes When it is Taken Once a Week
Official title: A Trial Investigating the Pharmacokinetics and Pharmacodynamics of NNC0148-0287 C (Insulin 287) at Steady State Conditions in Subjects With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2018-10-30
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study compares the new long-acting insulin 287 with the marketed insulin glargine for use in type 1 diabetes. The study will test how insulin is taken up in your blood, how long it stays there and how the blood sugar is lowered. The participant will get both of the insulins in a random order. Insulin 287 is a new medicine while insulin glargine is already approved for the treatment of diabetes and can be prescribed by a doctor. The participant will get 8 weekly doses of insulin 287 and 14 daily doses of insulin glargine. There will also be a run-in period of 2 days to 4 weeks with daily doses of insulin glargine before you start the insulin 287 period. All doses will be injected under the skin. The study will last for about 16 to 24 weeks. The participant will have 27 visits with the study doctor.


Eligibility criteria: Inclusion Criteria:

* Male or female, aged 18-64 years (both inclusive) at the time of signing informed consent
* Diagnosed with type 1 diabetes mellitus greater than or equal to 1 year prior to the day of screening
* Current daily basal insulin treatment greater than or equal to 0.2 U/kg/day
* Body mass index between 18.5 and 29.0 kg/m\^2 (both inclusive)
* HbA1c less than or equal to 9.0%

Exclusion Criteria:

* History or presence of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal or endocrinological conditions. Subjects with complications associated to diabetes can be included only if they are judged to be mild by the investigator. Subjects with other comorbidities (e.g. dyslipidaemia, hypertension and hypothyroidism) can be included if they have a stable treatment and are in adequate control according to the judgement of the investigator- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice)
* Known or suspected hypersensitivity to trial products or related products

Primary outcomes:
measure: AUCI287,τ,SS - Area under the serum insulin 287 concentration-time curve during one dosing interval at steady state
timeFrame: From 0 to 168 hours after trial product administration (Day 50)
Secondary outcomes:
measure: AUCGIR,16-52h,SS (for insulin 287) - Area under the glucose infusion rate-time curve at steady state
timeFrame: From 16 to 52 hours after trial product administration (Day 50)
measure: AUCGIR,138-168h,SS (for insulin 287) - Area under the glucose infusion rate-time curve at steady state
timeFrame: From 138 to 168 hours after trial product administration (Day 50)
measure: GIRmax,16-52h, SS (for insulin 287) - Maximum observed glucose infusion rate at steady state
timeFrame: From 16 to 52 hours after trial product administration (Day 50)
measure: GIRmax,138-168h, SS (for insulin 287) - Maximum observed glucose infusion rate at steady state
timeFrame: From 138 to 168 hours after trial product administration (Day 50)
measure: AUCGIR,0-24h,SS (for insulin glargine) - Area under the glucose infusion rate-time curve at steady state
timeFrame: From 0 to 24 hours after trial product administration (Day 14)
measure: GIRmax,0-24h, SS (for insulin glargine) - Maximum observed glucose infusion rate at steady state
timeFrame: From 0 to 24 hours after trial product administration (Day 14)
measure: AUCI287,0-168h,FD (from insulin 287) - Area under the serum insulin 287 concentration-time curve after the first dose
timeFrame: From 0 to 168 hours after trial product administration (Day 1)
measure: Cmax,I287,FD (for insulin 287) - Maximum observed serum insulin 287 concentration after the first dose
timeFrame: From 0 to 168 hours after trial product administration (Day 1)
measure: tmax,I287,FD (for insulin 287) - Time to maximum observed serum insulin 287 concentration after the first dose
timeFrame: From 0 to 168 hours after trial product administration (Day 1)
measure: Cmax,I287,SS (for insulin 287) - Maximum observed serum insulin 287 concentration after the last dose
timeFrame: From 0 to 168 hours after trial product administration (Day 50)
measure: tmax,I287,SS (for insulin 287) - Time to maximum observed serum insulin 287 concentration after the last dose
timeFrame: From 0 to 168 hours after trial product administration (Day 50)
measure: t½,I287,SS (for insulin 287) - Terminal half-life for insulin 287 at steady state
timeFrame: Terminal part of the serum insulin 287 concentration-time curve where the curve is well approximated by a straight line on logarithmic scale after last trial product administration (Day 50)
measure: CI287,trough (for insulin 287) - Serum insulin 287 trough concentration
timeFrame: Measured at the end of each dosing interval 168 hours after trial product administration (Day 8, 15, 22, 29, 36, 43, 50 and 57)
measure: AUCIGlar,τ,SS (for insulin glargine) - Area under the serum insulin glargine concentration-time curve during one dosing interval at steady state
timeFrame: From 0 to 24 hours after trial product administration (Day 14)
measure: Cmax,IGlar,SS (for insulin glargine) - Maximum observed serum insulin glargine concentration at steady state
timeFrame: From 0 to 24 hours after trial product administration (Day 14)
measure: tmax,IGlar,SS (for insulin glargine) - Time to maximum observed serum insulin glargine concentration at steady state
timeFrame: From 0 to 24 hours after trial product administration (Day 14)
measure: CIGlar,trough (for insulin glargine) - Serum insulin glargine trough concentration
timeFrame: Measured at the end of each dosing interval 24 hours after trial product administration (Day 4, 7, 14 and 15)
measure: Number of adverse events (AEs)
timeFrame: From first trial product administration (Day 1) to end of last dosing interval (Day 57 for insulin 287, day 15 for IGlar)
measure: Number of hypoglycaemic episodes
timeFrame: From first trial product administration (Day 1) to end of last dosing interval (Day 57 for insulin 287, day 15 for IGlar)
measure: Change in anti-insulin 287 antibody level
timeFrame: From first insulin 287 administration (Day 1) to Follow-up visit (visit 25, day 106)
measure: Change in anti-insulin 287 antibody titres
timeFrame: From first insulin 287 administration (Day 1) to Follow-up visit (visit 25, day 106)
measure: Positive cross-reactive anti-human insulin antibodies
timeFrame: At the follow-up visit (Visit 25, day 106)
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References:
citation: Hovelmann U, Engberg S, Heise T, Kristensen NR, Norgreen L, Zijlstra E, Ribel-Madsen R. Pharmacokinetic and pharmacodynamic properties of once-weekly insulin icodec in individuals with type 1 diabetes. Diabetes Obes Metab. 2024 May;26(5):1941-1949. doi: 10.1111/dom.15510. Epub 2024 Feb 20.