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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

Phase 1
Completed
Conditions
Diabetes Mellitus, Type 1
Interventions
Drug: Insulin glargine U100
Registration Number
NCT03766854
Lead Sponsor
Novo Nordisk A/S
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Insulin 287 followed by insulin glargine U100Insulin glargine U100Run-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.
Insulin glargine U100 followed by insulin 287insulin icodecRun-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.
Insulin glargine U100 followed by insulin 287Insulin glargine U100Run-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.
Insulin 287 followed by insulin glargine U100insulin icodecRun-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.
Primary Outcome Measures
NameTimeMethod
AUCI287τ,SS - Area under the serum insulin 287 concentration-time curve during one dosing interval at steady stateFrom 0 to 168 hours after trial product administration (day 50)

Measured in pmol\*h/L

Secondary Outcome Measures
NameTimeMethod
Positive cross-reactive anti-human insulin antibodiesAt follow-up visit (day 106)

Yes/no. Number of participants who developed/not developed positive cross-reactive anti-human insulin antibodies.

Change in antiinsulin 287 antibody levelFrom first insulin 287 administration (day 1) to follow-up visit (day 106)

Measured in % B/T (percentage of bound tracer measured after precipitation to total tracer)

t1/2,I287,SS - Terminal half-life for insulin 287 at steady stateTerminal 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)

Measured in hours

CI287,trough - Serum insulin 287 trough concentrationMeasured at the end of each dosing interval 168 hours after dosing (day 8, 15, 22, 29, 36, 43, 50 and 57)

Measured in pmol/L

AUCIGlar,τ,SS - Area under the serum IGlar concentration-time curve during one dosing interval at steady stateFrom 0 to 24 hours after trial product administration (day 14)

Measured in pmol\*h/L

AUCGIR,0-24h,SS - Area under the glucose infusion rate-time curve at steady stateFrom 0 to 24 hours after trial product administration (day 14)

Measured in mg/kg

Number of hypoglycaemic episodesFrom first trial product administration (day 1) to end of last dosing interval (day 57 for insulin 287, day 15 for IGlar) excluding clamp days

Number of episodes

Change in antiinsulin 287 antibody titresFrom first insulin 287 administration (day 1) to follow-up visit (day 106)

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.

AUCI287,0-168,FD - Area under the serum insulin 287 concentration-time curve after the first doseFrom 0 to 168 hours after trial product administration (day 1)

Measured in pmol\*h/L

tmax,I287,FD - Time to maximum observed serum insulin 287 concentration after the first doseFrom 0 to 168 hours after trial product administration (day 1)

Measured in hours

Cmax,I287,FD - Maximum observed serum insulin 287 concentration after the first doseFrom 0 to 168 hours after trial product administration (day 1)

Measured in pmol/L

Number of adverse events (AEs)From first trial product administration (day 1) to end of last dosing interval (day 57 for insulin 287, day 15 for IGlar)

Number of events

tmax,IGlar,SS - Time to maximum observed serum IGlar concentration at steady stateFrom 0 to 24 hours from trial product administration (day 14)

Measured in hours

CIGlar,trough - Serum IGlar trough concentrationMeasured at the end of each dosing interval 24 hours after trial product administration (day 7, 14 and 15)

Measured in pmol/L

GIRmax,24-48h, SS - Maximum observed glucose infusion rate at steady stateFrom 24 to 48 hours after trial product administration (day 51)

Measured in mg/(kg\*min)

AUCGIR,150-168h,SS - Area under the glucose infusion rate-time curve at steady stateFrom 150 to 168 hours after trial product administration (day 57)

Measured in mg/kg

GIRmax,0-24h,SS - Maximum observed glucose infusion rate at steady stateFrom 0 to 24 hours after trial product administration (day 14)

Measured in mg/(kg\*min)

tmax,I287,SS - Time to maximum observed serum insulin 287 concentration after the last doseFrom 0 to 168 hours after trial product administration (day 50)

Measured in hours

Cmax,I287,SS - Maximum observed serum insulin 287 concentration after the last doseFrom 0 to 168 hours after trial product administration (day 50)

Measured in pmol/L

Cmax,IGlar,SS - Maximum observed serum IGlar concentration at steady stateFrom 0 to 24 hours after trial product administration (day 14)

Measured in pmol/L

AUCGIR,24-48h,SS - Area under the glucose infusion rate-time curve at steady stateFrom 24 to 48 hours after trial product administration (day 51)

Measured in mg/kg

GIRmax,150-168h,SS - Maximum observed glucose infusion rate at steady stateFrom 150 to 168 hours after trial product administration (day 57)

Measured in mg/(kg\*min)

Trial Locations

Locations (1)

Novo Nordisk Investigational Site

🇯🇵

Fukuoka, Japan

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