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临床试验/NCT02269735
NCT02269735已完成1 期

A Three-part Study Parts I, II and III: Rising Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Healthy Subjects (Part I) and Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of MK-2640 in Subjects With Type 1 Diabetes Mellitus (Part II and Part III).

Merck Sharp & Dohme LLC0 个研究点目标入组 74 人开始时间: 2014年11月26日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
入组人数
74
主要终点
Number of participants who experienced an adverse event
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

The purpose of Part I of this study is to evaluate the safety and tolerability of intravenous (IV) doses of MK-2640 in healthy participants and to obtain preliminary plasma pharmacokinetic profiles of MK-2640. The purpose of Parts II and III of this study is to evaluate the safety and tolerability of IV doses of MK-2640 and regular human insulin (RHI), and to evaluate the pharmacokinetic and pharmacodynamic profile of MK-2640 and RHI in participants with type 1 diabetes mellitus (T1DM). Part II will be initiated only if Part I general safety, tolerability and other observed data are supportive of progression to Part II. Part III will be initiated only if Parts I and II general safety, tolerability and other observed data are supportive of progression to Part III.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 55 Years（Adult）
性别
All
接受健康志愿者
是

入选标准

  • 未提供

排除标准

  • •is mentally or legally incapacitated, or has significant emotional problems at the time of screening visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years
  • •has a history of clinically significant endocrine (except T1DM for Part II subjects), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases
  • •is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
  • •has a history of cancer (malignancy), except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix
  • •has a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food, had major surgery, donated or lost 1 unit of blood within 4 weeks prior to the screening visit
  • •has participated in another investigational trial within 4 weeks prior to the screening visit
  • •is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies beginning approximately 2 weeks prior to administration of the initial dose of trial drug, throughout the trial, until the posttrial visit
  • •consumes greater than 3 glasses of alcoholic beverages daily
  • •consumes greater than 6 servings of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.
  • •is currently a regular or recreational user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months
  • •Exclusion Criteria (Parts II and III):
  • •has a history of diabetic ketoacidosis in the last 6 months.
  • •has had one or more severe hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness within 2 weeks prior to dosing
  • •has used systemic (intravenous, oral, inhaled) glucocorticoids within 3 months of screening or is anticipated to require treatment with systemic glucocorticoids during study participation
  • •has a history of hypersensitivity to pharmacologic insulins or to any of the inactive ingredients in regular human insulin, or to any E. coli-derived drug product

研究组 & 干预措施

Part I: MK-2640 (Panel A)

Experimental

Part I: Lowest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: MK-2640 (Drug)

Part I: MK-2640 (Panel A)

Experimental

Part I: Lowest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Dextrose (Drug)

Part I: MK-2640 (Panel A)

Experimental

Part I: Lowest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Rescue medication (Drug)

Part I: MK-2640 (Panel B)

Experimental

Part I: Low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: MK-2640 (Drug)

Part I: MK-2640 (Panel B)

Experimental

Part I: Low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Dextrose (Drug)

Part I: MK-2640 (Panel B)

Experimental

Part I: Low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Rescue medication (Drug)

Part I: MK-2640 (Panel C)

Experimental

Part I: Medium-low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: MK-2640 (Drug)

Part I: MK-2640 (Panel C)

Experimental

Part I: Medium-low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Dextrose (Drug)

Part I: MK-2640 (Panel C)

Experimental

Part I: Medium-low dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Rescue medication (Drug)

Part I: MK-2640 (Panel D)

Experimental

Part I: Medium dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: MK-2640 (Drug)

Part I: MK-2640 (Panel D)

Experimental

Part I: Medium dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Dextrose (Drug)

Part I: MK-2640 (Panel D)

Experimental

Part I: Medium dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Rescue medication (Drug)

Part I: MK-2640 (Panel E)

Experimental

Part I: Medium-high dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: MK-2640 (Drug)

Part I: MK-2640 (Panel E)

Experimental

Part I: Medium-high dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Dextrose (Drug)

Part I: MK-2640 (Panel E)

Experimental

Part I: Medium-high dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Rescue medication (Drug)

Part I: MK-2640 (Panel F)

Experimental

Part I: High dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: MK-2640 (Drug)

Part I: MK-2640 (Panel F)

Experimental

Part I: High dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Dextrose (Drug)

Part I: MK-2640 (Panel F)

Experimental

Part I: High dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Rescue medication (Drug)

Part I: MK-2640 (Panel G)

Experimental

Part 1: Highest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: MK-2640 (Drug)

Part I: MK-2640 (Panel G)

Experimental

Part 1: Highest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Dextrose (Drug)

Part I: MK-2640 (Panel G)

Experimental

Part 1: Highest dose of MK-2640 infusion (3 approximately three-hour infusions at escalating rates) and dextrose infusion for 9 hours.

干预措施: Rescue medication (Drug)

Part II: MK-2640 followed by RHI

Experimental

Part II: MK-2640 infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: MK-2640 (Drug)

Part II: MK-2640 followed by RHI

Experimental

Part II: MK-2640 infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Regular Human Insulin (RHI) (Biological)

Part II: MK-2640 followed by RHI

Experimental

Part II: MK-2640 infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Dextrose (Drug)

Part II: MK-2640 followed by RHI

Experimental

Part II: MK-2640 infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Insulin aspart (Biological)

Part II: MK-2640 followed by RHI

Experimental

Part II: MK-2640 infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Rescue medication (Drug)

Part II: RHI followed by MK-2640

Experimental

Part II: RHI infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: MK-2640 (Drug)

Part II: RHI followed by MK-2640

Experimental

Part II: RHI infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Regular Human Insulin (RHI) (Biological)

Part II: RHI followed by MK-2640

Experimental

Part II: RHI infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Dextrose (Drug)

Part II: RHI followed by MK-2640

Experimental

Part II: RHI infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Insulin aspart (Biological)

Part II: RHI followed by MK-2640

Experimental

Part II: RHI infusion and dextrose infusion for 9 hours during Period 1 of Part II followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 9 hours during Period 2 of Part II. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part II.

干预措施: Rescue medication (Drug)

Part III: MK-2640 followed by RHI

Experimental

Part III: MK-2640 infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: MK-2640 (Drug)

Part III: MK-2640 followed by RHI

Experimental

Part III: MK-2640 infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Regular Human Insulin (RHI) (Biological)

Part III: MK-2640 followed by RHI

Experimental

Part III: MK-2640 infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Dextrose (Drug)

Part III: MK-2640 followed by RHI

Experimental

Part III: MK-2640 infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Insulin aspart (Biological)

Part III: MK-2640 followed by RHI

Experimental

Part III: MK-2640 infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by RHI infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Rescue medication (Drug)

Part III: RHI followed by MK-2640

Experimental

Part III: RHI infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: MK-2640 (Drug)

Part III: RHI followed by MK-2640

Experimental

Part III: RHI infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Regular Human Insulin (RHI) (Biological)

Part III: RHI followed by MK-2640

Experimental

Part III: RHI infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Dextrose (Drug)

Part III: RHI followed by MK-2640

Experimental

Part III: RHI infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Insulin aspart (Biological)

Part III: RHI followed by MK-2640

Experimental

Part III: RHI infusion and dextrose infusion for 7 hours during Period 1 of Part III followed by a 7-day wash-out period followed by MK-2640 infusion and dextrose infusion for 7 hours during Period 2 of Part III. Insulin aspart administered approximately 10 hours before Periods 1 and 2 of Part III.

干预措施: Rescue medication (Drug)

结局指标

主要结局

Number of participants who experienced an adverse event

时间窗: Up to 30 days following last dose

Pharmacokinetic parameter: steady state plasma concentration (Css)

时间窗: Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval

Pharmacokinetic parameter: area under the plasma concentration curve from time 0 to infinity (AUC [0 to infinity])

时间窗: Part I: 18 time points between predose and 600 minutes (min.); Part II: 19 time points between predose and 535 min.; Part III: 18 time points between predose and 415 min. following start of infusion

Pharmacokinetic parameter: clearance (CL)

时间窗: Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval

Pharmacokinetic parameter: volume of distribution (Vd)

时间窗: Part I: final 30 minutes of each infusion rate; Parts II and III: final 30 minutes of each interval

Pharmacokinetic parameter: plasma apparent terminal half-life

时间窗: Part II: following 9 hour infusion; Part III: following 7 hour infusion

Pharmacodynamic parameter: steady-state glucose infusion-rate (GIR) in Part II

时间窗: Part II: during the final 60 minutes of the infusion

Number of participants who discontinued study drug due to an adverse event

时间窗: Part I: 1 day; Parts II and III: 9 days

次要结局

  • Number of participants with anti-drug antibody (ADA) formation(Up to 30 days following last dose)

研究者

申办方类型
Industry
责任方
Sponsor

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