A Research Study of How Different Amounts of a New Medicine NNC0148-0287 C (Insulin 287) Works on the Blood Sugar of People Who Are Japanese With Type 1 Diabetes When Given Once a Week

A Multiple-dose Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NNC0148-0287 C (Insulin 287) for Subcutaneous Administration in Japanese Subjects With Type 1 Diabetes

This study will look at how insulin 287 works, if it is safe and the side effects in people who are Japanese with type 1 diabetes. The study will test how insulin goes through your blood, how long it stays there and how the blood sugar is lowered. Insulin 287 is a new medicine. Insulin glargine is already approved to treat diabetes. The study doctors can prescribe insulin glargine. The participants will get both of the insulins in a random order. The participants 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 7 weeks when the participants inject insulin glargine every day before they start insulin 287 period or insulin glargine period. All doses will be injected under the skin. During the run-in period, the participants adjust the insulin glargine dose and make their blood sugar levels stable. From the run-in period, the participants will take insulin aspart as bolus insulin. The study will last for about 16 - 28 weeks. The participants will have 24 visits with the study doctor. There will be 3 glucose clamps where the participants' blood sugar is tested over time. The participants cannot be in the study if the study doctor thinks that there are risks for their health.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-0025
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, Japanese subjects, aged 20 - 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 28.0 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 (except conditions associated with diabetes mellitus).
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods.
• 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 7 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 (PK) 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 (s.c.) injections of insulin 287 once weekly for 8 weeks; Other Names: Insulin 287; Drug: Insulin glargine U100; Participants will receive s.c. injections of insulin glargine once weekly for 2 weeks
Experimental: Insulin glargine U100 followed by insulin 287; Run-in period (2 days to 7 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 OW for 8 weeks and subsequent 4 weeks of terminal PK sampling.	Drug: insulin icodec; Participants will receive subcutaneous (s.c.) injections of insulin 287 once weekly for 8 weeks; Other Names: Insulin 287; Drug: Insulin glargine U100; Participants will receive s.c. injections of insulin glargine once weekly for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCI287τ,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
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) excluding clamp days
Change in antiinsulin 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 (day 106)
Change in antiinsulin 287 antibody titres	Number of dilutions. The antibody titer is calculated by diluting the blood serum sample containing antibody in serial ratios (1:2, 1:4, 1:8, 1:16... and so on). Using an appropriate detection method (e.g., colorimetric, chromatographic, etc.), each dilution is tested for the presence of detectable levels of antibody. The assigned titer value is indicative of the last dilution in which the antibody was detected.	From first insulin 287 administration (day 1) to follow-up visit (day 106)
Positive cross-reactive anti-human insulin antibodies	Yes/no. Number of participants who developed/not developed positive cross-reactive anti-human insulin antibodies.	At follow-up visit (day 106)
AUCI287,0-168,FD - 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)
tmax,I287,FD - 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,FD - 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,SS - 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)
Cmax,I287,SS - 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)
t1/2,I287,SS - 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 - Serum insulin 287 trough concentration	Measured in pmol/L	Measured at the end of each dosing interval 168 hours after dosing (day 8, 15, 22, 29, 36, 43, 50 and 57)
AUCIGlar,τ,SS - Area under the serum IGlar 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 - Maximum observed serum IGlar concentration at steady state	Measured in pmol/L	From 0 to 24 hours after trial product administration (day 14)
tmax,IGlar,SS - Time to maximum observed serum IGlar concentration at steady state	Measured in hours	From 0 to 24 hours from trial product administration (day 14)
CIGlar,trough - Serum IGlar trough concentration	Measured in pmol/L	Measured at the end of each dosing interval 24 hours after trial product administration (day 7, 14 and 15)
AUCGIR,24-48h,SS - Area under the glucose infusion rate-time curve at steady state	Measured in mg/kg	From 24 to 48 hours after trial product administration (day 51)
GIRmax,24-48h, SS - Maximum observed glucose infusion rate at steady state	Measured in mg/(kg*min)	From 24 to 48 hours after trial product administration (day 51)
AUCGIR,150-168h,SS - Area under the glucose infusion rate-time curve at steady state	Measured in mg/kg	From 150 to 168 hours after trial product administration (day 57)
GIRmax,150-168h,SS - Maximum observed glucose infusion rate at steady state	Measured in mg/(kg*min)	From 150 to 168 hours after trial product administration (day 57)
AUCGIR,0-24h,SS - 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 - Maximum observed glucose infusion rate at steady state	Measured in mg/(kg*min)	From 0 to 24 hours after trial product administration (day 14)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2018
• Primary Completion (Actual): December 9, 2019
• Study Completion (Actual): December 9, 2019

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

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; Insulin Glargine
• Other Study ID Numbers: NN1436-4422; U1111-1211-7635 (Other Identifier: World Health Organization (WHO))

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