Pharmacology of Rapid-acting Insulin Injected by Needle-free Jet-injection in Patients With Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- BG-AUC0-2h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion.
研究概览
简要总结
A previous study showed that absorption and glucose-lowering action of rapid-acting insulin analogues occurred twice as fast when these analogues were administered by jet injection technology rather than by conventional insulin pen in healthy non-diabetic subjects. This study investigates if the rapid-acting insulin analogue aspart (Novorapid®) injected with jet-injection or a conventional insulin pen prior to a standardised meal in patients with diabetes shows the same difference in the pharmacokinetic and pharmacodynamic profile.
详细描述
A previous study showed that absorption and glucose-lowering action of rapid-acting insulin analogues occurred twice as fast when these analogues were administered by jet injection technology rather than by conventional insulin pen in healthy non-diabetic subjects. This study investigates if the rapid-acting insulin analogue aspart (Novorapid®) injected with jet-injection or a conventional insulin pen prior to a standardised meal in patients with diabetes (type 1 and type 2) shows the same difference in the pharmacokinetic and pharmacodynamic profile.The pharmacokinetic and pharmacodynamic profile of insulin aspart will be derived from the time-action profiles of insulin and glucose, respectively, in response to insulin injected directly prior to a standardised meal. All patients will be investigated twice, where on one occasion the jet-injector device will be used to inject an individualised dose of insulin and a conventional insulin pen to inject a placebo solution, and on the other occasion insulin will be injected with the conventional pen and placebo with the jet-injector. The order of these occasions will be randomised and blinded to both the investigator and the participating patient. The primary endpoint is the hyperglycaemic burden as reflected by area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion (BG-AUC0-2h). Secondary study endpoints are the area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h (BG-AUC0-6h), maximal glucose excursion (BGmax), time to maximal glucose excursion (T-BGmax), time until plasma glucose has returned to baseline (T-BGBL), maximal insulin concentration (C-INSmax), time to maximal insulin concentration (T-INSmax), area under the insulin concentration curve (INSAUC) and time until 50% of insulin absorption (T-INSAUC50%) after insulin injection and meal ingestion.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body-mass index 18-32 kg/m2
- •Stable glycaemic control with HbA1c 6.0-9.0%
- •Duration of diabetes >1 year
- •Insulin use at least once daily or with subcutaneous pump
- •Blood pressure <160/90 mmHg
排除标准
- •Inability to provide informed consent
- •Requirement of <8 units of rapid-acting insulin (analogue) before meals
- •Chronic use of sulphonylurea derivatives, GLP-1 based treatments, acarbose or thiazolidinediones
- •Treatment with prednisolone, non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents, cytostatic drugs, hormone therapy except insulin, thyroid supplementation and oral anticonceptives
- •Known allergy to aspart insulin
- •Symptomatic diabetic neuropathy
- •History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty) in the past 6 months
- •Pregnancy or the intention to become pregnant
结局指标
主要结局
BG-AUC0-2h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion.
时间窗: 2 days (2 hours per day)
based on plasma glucose levels during the first two hours of the 6-hour post-meal study duration
次要结局
- BGmax (mmol/l): maximal glucose excursion after insulin injection and meal ingestion(2 days (6 hours each day))
- T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion(2 days (6 hours per day))
- BG-AUC0-6h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h after insulin injection and meal ingestion(2 days (6 hours each day))
- T-BGBL (min): time until plasma glucose has returned to baseline values after insulin injection and meal ingestion(2 days (6 hours per day))
- T-INSmax (min): time to maximal insulin concentration (C-INSmax)(2 days (6 hours per day))
- INSAUC (pmol•min-1•l-1): area under the insulin concentration curve (from timepoint 0)(2 days (6 hours per day))
- T-INSAUC50% (min): time until 50% of insulin absorption (mean residence time, MRT)(2 days (6 hours each day))
- Number of patients requiring exogenous glucose infusion to prevent postprandial hypoglycaemia after insulin injection and meal ingestion(2 days)
- Amount of exogenous glucose required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion(2 days)
- Duration of time that exogenous glucose is required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion(2 days)
- BG-AUC0-1h(2 days (6 hours per day))