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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- AUCI287τ,SS - Area under the serum insulin 287 concentration-time curve during one dosing interval at steady state
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: insulin icodec (Drug)
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.
干预措施: Insulin glargine U100 (Drug)
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.
干预措施: insulin icodec (Drug)
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.
干预措施: Insulin glargine U100 (Drug)
结局指标
主要结局
AUCI287τ,SS - Area under the serum insulin 287 concentration-time curve during one dosing interval at steady state
时间窗: From 0 to 168 hours after trial product administration (day 50)
Measured in pmol\*h/L
次要结局
- Positive cross-reactive anti-human insulin antibodies(At follow-up visit (day 106))
- Change in antiinsulin 287 antibody level(From first insulin 287 administration (day 1) to follow-up visit (day 106))
- t1/2,I287,SS - Terminal half-life for insulin 287 at steady state(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 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(From 0 to 24 hours after trial product administration (day 14))
- AUCGIR,0-24h,SS - Area under the glucose infusion rate-time curve at steady state(From 0 to 24 hours after trial product administration (day 14))
- Number of hypoglycaemic 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 titres(From first insulin 287 administration (day 1) to follow-up visit (day 106))
- AUCI287,0-168,FD - Area under the serum insulin 287 concentration-time curve after the first dose(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(From 0 to 168 hours after trial product administration (day 1))
- Cmax,I287,FD - Maximum observed serum insulin 287 concentration after the first dose(From 0 to 168 hours after trial product administration (day 1))
- 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))
- tmax,IGlar,SS - Time to maximum observed serum IGlar concentration at steady state(From 0 to 24 hours from trial product administration (day 14))
- CIGlar,trough - Serum IGlar trough concentration(Measured at the end of each dosing interval 24 hours after trial product administration (day 7, 14 and 15))
- GIRmax,24-48h, SS - Maximum observed glucose infusion rate at steady state(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(From 150 to 168 hours after trial product administration (day 57))
- GIRmax,0-24h,SS - Maximum observed glucose infusion rate at steady state(From 0 to 24 hours after trial product administration (day 14))
- tmax,I287,SS - Time to maximum observed serum insulin 287 concentration after the last dose(From 0 to 168 hours after trial product administration (day 50))
- Cmax,I287,SS - Maximum observed serum insulin 287 concentration after the last dose(From 0 to 168 hours after trial product administration (day 50))
- Cmax,IGlar,SS - Maximum observed serum IGlar concentration at steady state(From 0 to 24 hours after trial product administration (day 14))
- AUCGIR,24-48h,SS - Area under the glucose infusion rate-time curve at steady state(From 24 to 48 hours after trial product administration (day 51))
- GIRmax,150-168h,SS - Maximum observed glucose infusion rate at steady state(From 150 to 168 hours after trial product administration (day 57))