A Comparison of LY2605541 Once Daily at a Fixed Time With LY2605541 Variable Time of Dosing in Participants With Type 1 Diabetes Mellitus: An Open Label, Randomized, Crossover Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 212
- 试验地点
- 1
- 主要终点
- Hemoglobin A1c (HbA1c) at 12 Weeks
研究概览
简要总结
The primary purpose of participation in this study is to compare the safety and efficacy of different dosing schedules of LY2605541 and how different dosing schedules of LY2605541 affect Hemoglobin A1c (HbA1c). Participants will be treated for up to 36 weeks with LY2605541 (one 12-week Lead-in period and two 12-week Randomization periods) and will participate in a total of 42 weeks of total study enrollment, including a 2-week Screening period and a 4-week Follow-up period.
详细描述
This study involved a comparison of LY2605541 regimens, each administered with bolus insulin lispro. Eligible participants were switched to a fixed evening LY2605541dosing regimen at the beginning of the 12-week lead-in period. LY2605541 was administered SQ once-daily using a prefilled insulin device. The LY2605541dose was adjusted using a dosing algorithm adapted from Bartley and Bolli (Bartley et al. 2008, Bolli et al. 2009) based on the participant's blood glucose (BG) values and documented hypoglycemia during the previous week. Participants not already receiving insulin lispro for prandial dosing were switched to insulin lispro at the beginning of the 12-week lead-in period. Adjustments to insulin lispro doses were based on the insulin dosing algorithms adapted from Riddle and Bergenstal (Riddle et al. 2003, Bergenstal et al. 2008). At the time of randomization, participants were randomized to begin either the fixed evening dosing regimen or the variable time dosing regimen. Each participant was crossed over to the alternate regimen after 12 weeks. The insulin device (prefilled pen) remained the same throughout the study.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 diabetes mellitus for at least 1 year
- •Have an HbA1c value <9.0%
- •Have a body mass index (BMI) ≤35.0 kilogram per square meter (kg/m^2)
- •Currently using basal/ bolus insulin
- •Women of childbearing potential are not breastfeeding and must use methods to prevent pregnancy
排除标准
- •Have excessive insulin resistance
- •Are taking medications other than insulin for diabetes
- •High triglycerides
- •Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia as determined by the investigator) within 6 months prior to entry into the study
- •Have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemia or diabetic ketoacidosis) in the past 6 months
- •Have cardiac disease with functional status that is New York Heart Association (NYHA) Class III or IV (per NYHA Cardiac Disease Classification)
- •Have impaired renal function
- •Have impaired liver function
- •Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with HbA1c measurement
- •Have cancer, recent cancer, or risk of cancer
- •Have a known hypersensitivity or allergy to any of the study insulins or their excipients
- •Have chronic systemic glucocorticoid users
- •Have clinically significant diabetic autonomic neuropathy
- •Have irregular sleep/wake cycle
- •Have been treated with a drug within the last 30 days that has not received regulatory approval at the time of study entry
- •Prior study participation
- •Are using or have used niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening
研究组 & 干预措施
LY2605541 Fixed Time Dosing
Participant-specific dose of LY2605541 administered subcutaneously (SQ) at approximately the same time every evening for 12 weeks in the Lead-in Period and in Randomization Period 1 or Randomization Period 2.
Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal).
Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on self-monitored blood glucose (SMBG). Target glucose values were as follows:
Preprandial and bedtime BG between 71 and 130 milligrams/deciliter (mg/dL) Insulin adjustment and glucose correction between 71 and 100 mg/dL.
干预措施: LY2605541 (Drug)
LY2605541 Fixed Time Dosing
Participant-specific dose of LY2605541 administered subcutaneously (SQ) at approximately the same time every evening for 12 weeks in the Lead-in Period and in Randomization Period 1 or Randomization Period 2.
Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal).
Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on self-monitored blood glucose (SMBG). Target glucose values were as follows:
Preprandial and bedtime BG between 71 and 130 milligrams/deciliter (mg/dL) Insulin adjustment and glucose correction between 71 and 100 mg/dL.
干预措施: Insulin Lispro (Drug)
LY2605541 Variable Time Dosing
Participant-specific dose of LY2605541 administered SQ on a variable time schedule (8- and 40-hour dosing intervals) for 12 weeks in Randomization Period 1 or Randomization Period 2. Dosing schedules were to remain approximately the same throughout the 12 weeks.
Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal).
Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows:
Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL.
干预措施: LY2605541 (Drug)
LY2605541 Variable Time Dosing
Participant-specific dose of LY2605541 administered SQ on a variable time schedule (8- and 40-hour dosing intervals) for 12 weeks in Randomization Period 1 or Randomization Period 2. Dosing schedules were to remain approximately the same throughout the 12 weeks.
Participant-specific dose of insulin lispro SQ when >20% of calories were consumed (pre-meal).
Insulin dose and adjustments to insulin dose were determined by insulin algorithms based on SMBG. Target glucose values were as follows:
Preprandial and bedtime BG between 71 and 130 mg/dL Insulin adjustment and glucose correction between 71 and 100 mg/dL.
干预措施: Insulin Lispro (Drug)
结局指标
主要结局
Hemoglobin A1c (HbA1c) at 12 Weeks
时间窗: At 12 Week in Each Randomization Period
HbA1c is a test that measures a person's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction.
次要结局
- 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events(Baseline (Day 1) of Randomization Period through 24 Weeks (12 weeks in each Randomization Period))
- Intra-participant Variability in SMBG at 12 Weeks(At 12 Week in Each Randomization Period)
- Change From Day 1 of Lead-In Period to 36 Weeks in Body Weight(Day 1 of Lead-In Period, 36 Weeks)
- Participants With Treatment-Emergent Anti-LY2605541 Antibody Response(Day 1 of Lead-in Period through 36 Weeks)
- Percentage of Participants With Total and Nocturnal Hypoglycemic Events(Baseline (Day 1) of Randomization Period through 24 weeks (12 weeks in each Randomization Period))
- Intra-Participant Variability of FBG at 12 Weeks(At 12 Weeks in Each Randomization Period)
- Fasting Serum Glucose (FSG) at 12 Weeks(At 12 Weeks in Each Randomization Period)
- Change From Randomization to 12 Weeks in 9-Point SMBG(Randomization, 12 Weeks in Each Randomization Period)
- Fasting Blood Glucose (FBG) Measured by Self-Monitored Blood Glucose(At 12 Weeks in Each Randomization Period)
- Change From Randomization to 12 Weeks in HbA1c(Randomization, 12 Weeks in Each Randomization Period)
- Basal, Bolus, and Total Insulin Doses at 12 Weeks(At 12 Weeks in Each Randomization Period)
- 0300-Hour Blood Glucose to Fasting Blood Glucose Excursion(At 12 Week in Each Randomization Period)
- Self-Monitored Blood Glucose (SMBG) at 12 Weeks(At 12 Week in Each Randomization Period)
- Change From Randomization to 12 Weeks in Body Weight(Randomization, 12 Weeks in Each Randomization Period)
- Change From Day 1 of Lead-in to 36 Weeks in Triglycerides, Total Cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C)(Day 1 of Lead-In Period, 36 Weeks)
- Proportion of Bolus to Total Insulin Doses at 12 Weeks(At 12 Weeks in Each Randomization Period)
- Percentage of Participants With HbA1c <7.0% and ≤6.5% at 12 Weeks(At 12 Weeks in Each Randomization Period)