Subcutaneous Pharmacokinetic Evaluation of Monomeric Insulin and Lyumjev in Adults With Type 1 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Time to Maximum Insulin Concentration (Tmax)
研究概览
简要总结
The SPEED study is a randomized, crossover pilot study evaluating the pharmacokinetics of novel insulin formulations in adults with type 1 diabetes. The study compares two experimental insulin formulations (diluted U-200 Humalog and U-500 Humulin with sterile water, mannitol and EDTA) against commercially available U-100 Lyumjev to determine if these modifications can improve insulin onset and duration of action.
Twenty participants will complete three study visits, each separated by at least48 hours. At each visit, participants will receive one of the three insulin formulations (0.20 u/kg) via subcutaneous injection following consumption of a standardized mixed meal. Blood samples will be collected frequently over 6 hours to measure insulin concentrations and assess pharmacokinetic parameters, including time to maximum concentration (Tmax), maximum concentration (Cmax), elimination half-life, and area under the curve.
The study aims to address limitations of current insulin formulations used in automated insulin delivery systems, which are too slow to provide optimal meal coverage without pre-meal dosing. By reducing zinc content through EDTA chelation and decreasing metacresol concentration through dilution, these novel formulations may offer faster onset and shorter duration of action, potentially improving glucose control in people with type 1 diabetes using insulin pump therapy.
详细描述
Background and Rationale Current rapid-acting insulin formulations used in automated insulin delivery systems are limited by slow pharmacokinetics that prevent optimal meal coverage without pre-meal announcement. These insulins are predominantly composed of hexamers (94%) when stored, which must dissociate to monomers for biological activity. The presence of zinc ions and metacresol in commercial formulations promotes hexamer stability, contributing to slower onset and prolonged duration of action.
This study evaluates a two-pronged approach to improve insulin pharmacokinetics: (1) zinc removal through EDTA chelation, and (2) metacresol concentration reduction through dilution. Previous research has shown that these modifications can improve oligomer composition and potentially enhance insulin action speed and duration.
Study Design This is a randomized, crossover, single-dose, within-subject pilot study. Each participant serves as their own control, receiving all three insulin formulations in randomized order across three separate visits.
Target Enrollment: 10 participants
Key Inclusion Criteria
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible for the study, a subject must meet all of the following criteria:
- •18-60 years of age
- •Clinical diagnosis of type 1 diabetes
- •On insulin pump therapy and continuous glucose monitor for at least 3 months
- •For females of childbearing potential, a negative pregnancy test and not attempting to conceive.
- •Understanding and willingness to follow the protocol and sign informed consent
- •Ability to speak, read and write English
排除标准
- •The presence of any of the following is an exclusion for the study:
- •Diabetic ketoacidosis within 3 months
- •Severe hypoglycemia resulting in seizure or loss of consciousness within 3 months prior to enrollment
- •Have donated blood within 8 weeks
- •Have a known clinically significant history of anemia
- •Pregnant or lactating
- •Active infection
- •Any medical condition that, in the investigator's opinion, might interfere with study completion or participant safety.
- •Known seizure disorder
- •Inpatient psychiatric treatment within 6 months
- •Medication instability within 1 month prior to enrollment, including antihypertensive, thyroid, antidepressant, or lipid-lowering medications
- •Suspected drug or alcohol abuse
- •Chronic kidney disease (GFR < 60 mL/min/1.73m²)
研究组 & 干预措施
Diluted Humalog U-200 Insulin
Participants will receive 0.20u/kg U-200 Humalog diluted 1:1 with sterile water, EDTA, and mannitol dilution buffer (final concentration U-100) through subcutaneous injection
干预措施: Diluted Humalog U-200 Insulin (Drug)
Lyumjev U-100 Insulin
Participants will receive 0.20 u/kg commercially available U-100 Lyumjev insulin (unmodified) through subcutaneous injection.
干预措施: Lyumjev U-100 Insulin (Drug)
Diluted Humalog U-200 Insulin
Participants will receive 0.20u/kg U-200 Humalog diluted 1:1 with sterile water, EDTA, and mannitol dilution buffer (final concentration U-100) through subcutaneous injection
干预措施: Boost Mixed Meal Test (Dietary Supplement)
Diluted Humulin U-500 Insulin
Participants will receive 0.20u/kg U-500 Humulin diluted 1:4 with sterile water, EDTA, and mannitol dilution buffer (final concentration U-100) through subcutaneous injection
干预措施: Diluted U-500 Humulin Insulin (Drug)
Diluted Humulin U-500 Insulin
Participants will receive 0.20u/kg U-500 Humulin diluted 1:4 with sterile water, EDTA, and mannitol dilution buffer (final concentration U-100) through subcutaneous injection
干预措施: Boost Mixed Meal Test (Dietary Supplement)
Lyumjev U-100 Insulin
Participants will receive 0.20 u/kg commercially available U-100 Lyumjev insulin (unmodified) through subcutaneous injection.
干预措施: Boost Mixed Meal Test (Dietary Supplement)
结局指标
主要结局
Time to Maximum Insulin Concentration (Tmax)
时间窗: 0 to 360 minutes post-injection
Time from insulin injection to maximum plasma insulin concentration for each insulin formulation, determined from frequent blood sampling data. Measured using validated enzyme-linked immunosorbent assay (ELISA).
Maximum Plasma Insulin Concentration (Cmax)
时间窗: 0 to 360 minutes post-injection
Peak plasma insulin concentration achieved for each insulin formulation, determined from frequent blood sampling data. Measured using validated enzyme-linked immunosorbent assay (ELISA).
Elimination Half-Life (T1/2)
时间窗: 0 to 360 minutes post-injection
Time required for plasma insulin concentration to decrease by 50% from maximum concentration for each insulin formulation, calculated from frequent blood sampling data. Measured using validated enzyme-linked immunosorbent assay (ELISA).
Area Under the Concentration-Time Curve (AUC)
时间窗: 0 to 360 minutes post-injection
Total drug exposure calculated as the area under the plasma insulin concentration-time curve using the trapezoidal rule. Provides a weighted sum of insulin concentration values over time for each formulation. Measured using validated enzyme-linked immunosorbent assay (ELISA)
次要结局
未报告次要终点
研究者
Rayhan A. Lal
Assistant Professor of Medicine & Pediatrics
Stanford University