A Single Dose Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-1293 and to Compare Its Pharmacologic Properties to Those of Another Basal Insulin in Subjects With Type I Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 主要终点
- Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
研究概览
简要总结
The purpose of this study is to assess the safety, pharmacokinetics, and pharmacodynamics of MK-1293 compared with a basal insulin (EU-Lantus™) in participants with Type 1 Diabetes. The primary hypotheses are that the duration of action, pharmacodynamic profile, and pharmacokinetic profile of MK-1293 and the comparator basal insulin are similar.
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, Investigator, Outcomes Assessor)
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
- •Has type 1 diabetes mellitus diagnosed at least 12 months before screening
- •Subject to investigator discretion, is on a stable dose of insulin for at least 2 weeks before screening
- •Has a total daily insulin dose <=1.2 units/kg
- •Has a screening hemoglobin A1c <9.5%
- •Has a body mass index >18.0 and <=30.0 kg/m^2
- •Has a weight >=50 kg
- •Female participant of reproductive potential has a serum beta-human chorionic gonadotropin level consistent with the nongravid state and agrees to use (and/or have her partner use) 2 acceptable methods of birth control until 2 weeks after the last dose of study drug
- •Postmenopausal female participant is without menses for >=1 year
- •Surgically sterile female participant status is post hysterectomy, oophorectomy, or tubal ligation
- •Has not used nicotine or nicotine-containing products for at least 3 months before study start or smokes less than 10 cigarettes per day and is willing to abstain during the trial
排除标准
- •Has a history of clinically significant gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or disease
- •Has a history of clinically significant endocrine abnormalities or diseases except type 1 diabetes mellitus
- •Has had any severe hypoglycemic episodes associated with hypoglycemic seizures, comas, or unconsciousness within the past 3 months
- •Has a history of diabetic ketoacidosis within the past 6 months
- •Has a history of significant multiple or severe allergies, anaphylactic reaction, or significant intolerability to drugs or food
- •Has a history of hypersensitivity to pharmacologic insulins
- •Is positive for hepatitis B surface antigen, hepatitis C, or Human Immunodeficiency Virus
- •Has had major surgery or donated or lost 1 unit of blood within 4 weeks before screening
- •Unable to refrain from use of any medication or herbal remedy from 2 weeks prior to the first dose of study drug to until the posttrial visit. Some medications are permitted and may be discussed with the investigators
- •Vaccination within 12 weeks of start of study participation
- •Consumes >3 glasses of alcoholic beverages per day. Participants consuming 4 glasses of alcoholic beverages may be enrolled at the discretion of the investigator.
- •Consumes >6 servings of caffeinated beverages per day
- •Is a regular user of any illicit drugs or has a history of drug abuse (including alcohol) within approximately 1 year
- •Is on a carbohydrate-restricted diet (<100 grams carbohydrate per day); participants who are on a carbohydrate-restricted diet may be included if they agree to a diet consisting of >=100 grams of carbohydrate daily throughout the study
- •Has a personal or family history of hypercoagulability or thromboembolic disease
- •Has used systemic glucocorticoids within 3 months of screening or anticipates treatment with systemic glucocorticoids during study participation.
研究组 & 干预措施
MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
干预措施: MK-1293 (Drug)
MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
干预措施: EU-Lantus™ (Drug)
MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
干预措施: Novolog™ (Drug)
EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
干预措施: MK-1293 (Drug)
EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
干预措施: EU-Lantus™ (Drug)
EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
干预措施: Novolog™ (Drug)
结局指标
主要结局
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
时间窗: Up to 30 hours postdose
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
时间窗: Up to 12 hours postdose
The area under the glucose infusion rate curve from hours 0 to 12 after injection (AUC\[GIR{0-12}\]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
时间窗: From 12 to 24 hours postdose
The area under the glucose infusion rate curve from hours 12 to 24 after injection (AUC\[GIR{12-24}\]) for participants who received either MK-1293 or Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Maximum Glucose Infusion Rate (GIRmax)
时间窗: Up to 30 hours postdose
Maximum glucose infusion rate (GIR\[max\]) based on smoothed data for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
时间窗: Up to 24 hours postdose
The area under the glucose infusion rate curve from hours 0 to 24 after injection (AUC\[GIR{0-24}\]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
时间窗: Up to 24 hours postdose
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Analysis was performed on log scale with results back transformed to the original scale
M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
时间窗: Up to 24 hours postdose
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Analysis was performed on log scale with results back transformed to original scale.
次要结局
- M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)(Up to 12 hours postdose)
- M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)(From 12 to 24 hours postdose)