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

A Trial Investigating the Pharmacokinetics and Pharmacodynamics of NNC0148-0287 C (Insulin 287) at Steady State Conditions in Subjects With Type 1 Diabetes

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Insulin icodec; Drug: IGlar U100

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin 287 followed by insulin glargine U100; Run-in period (2 days to 4 weeks): The basal insulin glargine dose for each subject will be established and optimised. After run-in, participants will receive insulin 287 once a week (OW) for 8 weeks and subsequent 4 weeks of terminal pharmacokinetic sampling where subjects are treated with once daily (OD) insulin glargine. After insulin 287 treatment, participants will receive insulin glargine U100 OD for 2 weeks.	Drug: Insulin icodec; Participants will receive subcutaneous injections of insulin 287 once weekly for 8 weeks; Other Names: Insulin 287; Drug: IGlar U100; Participants will receive subcutaneous injections of insulin glargine once weekly for 2 weeks.
Experimental: Insulin glargine U100 followed by insulin 287; Run-in period (2 days to 4 weeks): The basal insulin glargine dose for each subject will be established and optimised. After run-in, participants will receive insulin glargine U100 OD for 2 weeks followed by 1-14 days (at least 1 day is mandatory) of continued insulin glargine treatment. After insulin glargine treatment, participants will receive insulin 287 once a week (OW) for 8 weeks and subsequent 4 weeks of terminal pharmacokinetic sampling.	Drug: Insulin icodec; Participants will receive subcutaneous injections of insulin 287 once weekly for 8 weeks; Other Names: Insulin 287; Drug: IGlar U100; Participants will receive subcutaneous injections of insulin glargine once weekly for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCI287,τ,SS - Area under the serum insulin 287 concentration-time curve during one dosing interval at steady state	Measured in pmol*h/L	From 0 to 168 hours after trial product administration (Day 50)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCGIR,16-52h,SS (for insulin 287) - Area under the glucose infusion rate-time curve at steady state	Measured in mg/kg	From 16 to 52 hours after trial product administration (Day 50)
AUCGIR,138-168h,SS (for insulin 287) - Area under the glucose infusion rate-time curve at steady state	Measured in mg/kg	From 138 to 168 hours after trial product administration (Day 50)
GIRmax,16-52h, SS (for insulin 287) - Maximum observed glucose infusion rate at steady state	Measured in mg/(kg*min)	From 16 to 52 hours after trial product administration (Day 50)
GIRmax,138-168h, SS (for insulin 287) - Maximum observed glucose infusion rate at steady state	Measured in mg/(kg*min)	From 138 to 168 hours after trial product administration (Day 50)
AUCGIR,0-24h,SS (for insulin glargine) - Area under the glucose infusion rate-time curve at steady state	Measured in mg/kg	From 0 to 24 hours after trial product administration (Day 14)
GIRmax,0-24h, SS (for insulin glargine) - Maximum observed glucose infusion rate at steady state	Measured in mg/(kg*min)	From 0 to 24 hours after trial product administration (Day 14)
AUCI287,0-168h,FD (from insulin 287) - Area under the serum insulin 287 concentration-time curve after the first dose	Measured in pmol*h/L	From 0 to 168 hours after trial product administration (Day 1)
Cmax,I287,FD (for insulin 287) - Maximum observed serum insulin 287 concentration after the first dose	Measured in pmol/L	From 0 to 168 hours after trial product administration (Day 1)
tmax,I287,FD (for insulin 287) - Time to maximum observed serum insulin 287 concentration after the first dose	Measured in hours	From 0 to 168 hours after trial product administration (Day 1)
Cmax,I287,SS (for insulin 287) - Maximum observed serum insulin 287 concentration after the last dose	Measured in pmol/L	From 0 to 168 hours after trial product administration (Day 50)
tmax,I287,SS (for insulin 287) - Time to maximum observed serum insulin 287 concentration after the last dose	Measured in hours	From 0 to 168 hours after trial product administration (Day 50)
t½,I287,SS (for insulin 287) - Terminal half-life for insulin 287 at steady state	Measured in hours	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)
CI287,trough (for insulin 287) - Serum insulin 287 trough concentration	Measured in pmol/L	Measured at the end of each dosing interval 168 hours after trial product administration (Day 8, 15, 22, 29, 36, 43, 50 and 57)
AUCIGlar,τ,SS (for insulin glargine) - Area under the serum insulin glargine concentration-time curve during one dosing interval at steady state	Measured in pmol*h/L	From 0 to 24 hours after trial product administration (Day 14)
Cmax,IGlar,SS (for insulin glargine) - Maximum observed serum insulin glargine concentration at steady state	Measured in pmol/L	From 0 to 24 hours after trial product administration (Day 14)
tmax,IGlar,SS (for insulin glargine) - Time to maximum observed serum insulin glargine concentration at steady state	Measured in hours	From 0 to 24 hours after trial product administration (Day 14)
CIGlar,trough (for insulin glargine) - Serum insulin glargine trough concentration	Measured in pmol/L	Measured at the end of each dosing interval 24 hours after trial product administration (Day 4, 7, 14 and 15)
Number of adverse events (AEs)	Number of events	From first trial product administration (Day 1) to end of last dosing interval (Day 57 for insulin 287, day 15 for IGlar)
Number of hypoglycaemic episodes	Number of episodes	From first trial product administration (Day 1) to end of last dosing interval (Day 57 for insulin 287, day 15 for IGlar)
Change in anti-insulin 287 antibody level	Measured in % B/T (percentage of bound tracer measured after precipitation to total tracer)	From first insulin 287 administration (Day 1) to Follow-up visit (visit 25, day 106)
Change in anti-insulin 287 antibody titres	Number of dilutions	From first insulin 287 administration (Day 1) to Follow-up visit (visit 25, day 106)
Positive cross-reactive anti-human insulin antibodies	Number of patients with/without positive cross-reactive anti-human insulin antibodies	At the follow-up visit (Visit 25, day 106)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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 Feb 20. doi: 10.1111/dom.15510. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2018
• Primary Completion (Actual): June 26, 2020
• Study Completion (Actual): June 26, 2020

Study Registration Dates

• First Submitted: October 26, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 30, 2018

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: NN1436-4225; U1111-1204-8909 (Other Identifier: World Health Organization (WHO)); 2017-004528-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No