A Phase 4, Randomized, Double-Blind, 2-Way Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) With, Compared to Without, Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Early Insulin Exposure (%AUC[0-60])
研究概览
简要总结
The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 [rHuPH20]) injection at the time of infusion set insertion compared to sham injection.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females of age 18 to 65 years, inclusive. Females of child-bearing potential must use a standard and effective means of birth control for the duration of the study.
- •Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
- •Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive.
- •Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results.
- •Fasting connecting peptide of insulin (C-peptide) <0.6 nanograms per milliliter (ng/mL).
- •Current treatment with insulin <90 units per day (U/d).
- •Current use of rapid acting insulin analog.
- •Routine use of CSII as the primary route of insulin administration for at least 3 months prior to screening
- •Participants should be in good general health based on medical history and physical examination without medical conditions that might prevent the completion of study drug infusions and assessments required in the study protocol.
排除标准
- •Known or suspected allergy to any component of any of the study drugs in this study.
- •Previous enrollment in this study.
- •Use of drugs that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia. Participants taking maintenance doses of blood thinners (for example, coumadin or heparin) will be excluded.
- •Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II).
- •Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
- •Current addiction to alcohol or substances of abuse as determined by the Investigator.
- •Blood donation or phlebotomy (>500 milliliters [mL]) within the previous 8 weeks of the Screening Visit(s) in this study.
- •Pregnancy, breastfeeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device [IUD], oral or injectable contraceptives, or barrier methods).
- •Symptomatic gastroparesis.
- •Receipt of any investigational drug within 4 weeks of Study Day 1.
研究组 & 干预措施
Insulin (Aspart or Lispro)-Sham
In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16.
Each Phase was separated by a washout period of 5 to 21 days.
干预措施: Sham Injection (Drug)
Insulin (Aspart or Lispro)-Sham
In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16.
Each Phase was separated by a washout period of 5 to 21 days.
干预措施: Insulin aspart (Drug)
Insulin (Aspart or Lispro)-Sham
In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16.
Each Phase was separated by a washout period of 5 to 21 days.
干预措施: Insulin lispro (Drug)
Insulin (Aspart or Lispro)-rHuPH20
In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20).
Each Phase was separated by a washout period of 5 to 21 days.
干预措施: Recombinant human hyaluronidase PH20 (Drug)
Insulin (Aspart or Lispro)-rHuPH20
In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20).
Each Phase was separated by a washout period of 5 to 21 days.
干预措施: Insulin aspart (Drug)
Insulin (Aspart or Lispro)-rHuPH20
In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20).
Each Phase was separated by a washout period of 5 to 21 days.
干预措施: Insulin lispro (Drug)
结局指标
主要结局
Early Insulin Exposure (%AUC[0-60])
时间窗: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4
Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve \[AUC{0 360}\]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose during a euglycemic clamp.
次要结局
- Maximum Glucose Infusion Rate (GIRmax)(0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4)
- Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)(0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4)
- Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)(0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4)
- Time to 50% Total Glucose Infused (50%Gtot)(0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4)
- Duration of Insulin Action (AUMC[0-360]/AUC[0-360])(10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4)
- Area Under the Glucose Concentration Curve (AUC[0-360])(30 minutes and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4)