临床试验/NCT03170544

NCT03170544已完成1 期

A Single Ascending Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1092 in Healthy Subjects, Subjects With Type 1 Diabetes Mellitus, and Subjects With Type 2 Diabetes Mellitus.

Merck Sharp & Dohme LLC1 个研究点分布在 1 个国家目标入组 69 人开始时间: 2017年8月16日最近更新: 2019年11月15日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Merck Sharp & Dohme LLC
入组人数: 69
试验地点: 1
主要终点: Number of Participants Who Discontinued the Study Due to an AE

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研究点记录与标识符相似试验

研究概览

简要总结

This is an active- and placebo-controlled, single-site, four-part trial of MK-1092 in healthy adult participants, in participants with type 1 diabetes mellitus (T1DM), and in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis for this study is that at a dose with sufficient safety, the mean maximal glucose infusion rate (GIRmax) after single subcutaneous (SC) administration of MK-1092 in adult participants with T1DM is within an acceptable range. (Part 3)

详细描述

There will be 4 parts in this study. In Part 1, healthy adult participants will be randomized to receive blinded MK-1092 subcutaneously (SC) or glargine SC, as a single dose under the euglycemic clamp. Once a safe and tolerated dose that achieves GIRmax is identified in Part 1, Part 2 will start. In Part 2, 4 different healthy adult participants will be enrolled in a single panel and receive open-label MK-1092 SC as a single dose under the euglycemic clamp and also receive an intravenous infusion of Humalog®. In Part 3, adult participants with T1DM will be randomized to receive blinded MK-1092 SC or insulin glargine SC, as a single dose under the euglycemic clamp. Part 4 includes a 3-period (Periods 1, 2, and 3) design that will explore up to 3 single subcutaneous doses of MK-1092 or insulin glargine in participants with Type 2 diabetes mellitus.

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: Double (Participant, Investigator)

入排标准

年龄范围: 18 Years 至 60 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

未提供

排除标准

未提供

研究组 & 干预措施

Part 1, MK-1092, 4.0 nmol/kg

Experimental

MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: MK-1092, 4.0 nmol/kg (Drug)

Part 1, MK-1092, 4.0 nmol/kg

Experimental

MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Placebo to glargine (Drug)

Part 1, MK-1092, 4.0 nmol/kg

Experimental

MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Dextrose (Other)

Part 1, MK-1092, 8.0 nmol/kg

Experimental

MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: MK-1092, 8.0 nmol/kg (Drug)

Part 1, MK-1092, 8.0 nmol/kg

Experimental

MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Placebo to glargine (Drug)

Part 1, MK-1092, 8.0 nmol/kg

Experimental

MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Dextrose (Other)

Part 1, MK-1092, 16 nmol/kg

Experimental

MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: MK-1092, 16 nmol/kg (Drug)

Part 1, MK-1092, 16 nmol/kg

Experimental

MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Placebo to glargine (Drug)

Part 1, MK-1092, 16 nmol/kg

Experimental

MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Dextrose (Other)

Part 1, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: MK-1092, 32 nmol/kg (Drug)

Part 1, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Placebo to glargine (Drug)

Part 1, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Dextrose (Other)

Part 1, MK-1092, 64 nmol/kg

Experimental

MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: MK-1092, 64 nmol/kg (Drug)

Part 1, MK-1092, 64 nmol/kg

Experimental

MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Placebo to glargine (Drug)

Part 1, MK-1092, 64 nmol/kg

Experimental

MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Dextrose (Other)

Part 1, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Glargine 3.0 nmol/kg (Drug)

Part 1, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Placebo to MK-1092 (Drug)

Part 1, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants

干预措施: Dextrose (Other)

Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg

Experimental

MK-1092, 8.0 nmol/kg dose selection based on Part 1 + lispro (Humalog®), 1.2 nmol/kg, as a single dose, in healthy participants

干预措施: MK-1092, 8.0 nmol/kg (Drug)

Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg

Experimental

MK-1092, 8.0 nmol/kg dose selection based on Part 1 + lispro (Humalog®), 1.2 nmol/kg, as a single dose, in healthy participants

干预措施: Lispro 1.2 nmol/kg (Drug)

Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg

Experimental

MK-1092, 8.0 nmol/kg dose selection based on Part 1 + lispro (Humalog®), 1.2 nmol/kg, as a single dose, in healthy participants

干预措施: Dextrose (Other)

Part 3, MK-1092, 8.0 nmol/kg

Experimental

MK-1092, (8.0 nmol/kg based on Part 1), SC, in participants with T1DM.

干预措施: MK-1092, 8.0 nmol/kg (Drug)

Part 3, MK-1092, 8.0 nmol/kg

Experimental

MK-1092, (8.0 nmol/kg based on Part 1), SC, in participants with T1DM.

干预措施: Placebo to glargine (Drug)

Part 3, MK-1092, 8.0 nmol/kg

Experimental

MK-1092, (8.0 nmol/kg based on Part 1), SC, in participants with T1DM.

干预措施: Dextrose (Other)

Part 3, MK-1092, 8.0 nmol/kg

Experimental

MK-1092, (8.0 nmol/kg based on Part 1), SC, in participants with T1DM.

干预措施: Insulin (Biological)

Part 3, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: MK-1092, 32 nmol/kg (Drug)

Part 3, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: Placebo to glargine (Drug)

Part 3, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: Dextrose (Other)

Part 3, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: Insulin (Biological)

Part 3, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: Glargine 3.0 nmol/kg (Drug)

Part 3, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: Placebo to MK-1092 (Drug)

Part 3, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: Dextrose (Other)

Part 3, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T1DM

干预措施: Insulin (Biological)

Part 4, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: MK-1092, 32 nmol/kg (Drug)

Part 4, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Placebo to glargine (Drug)

Part 4, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Dextrose (Other)

Part 4, MK-1092, 32 nmol/kg

Experimental

MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Insulin (Biological)

Part 4, MK-1092, 16 nmol/kg

Experimental

MK-1092, 16 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: MK-1092, 16 nmol/kg (Drug)

Part 4, MK-1092, 16 nmol/kg

Experimental

MK-1092, 16 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Placebo to glargine (Drug)

Part 4, MK-1092, 16 nmol/kg

Experimental

MK-1092, 16 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Dextrose (Other)

Part 4, MK-1092, 16 nmol/kg

Experimental

MK-1092, 16 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Insulin (Biological)

Part 4, MK-1092, 64 nmol/kg

Experimental

MK-1092, 64 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: MK-1092, 64 nmol/kg (Drug)

Part 4, MK-1092, 64 nmol/kg

Experimental

MK-1092, 64 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Placebo to glargine (Drug)

Part 4, MK-1092, 64 nmol/kg

Experimental

MK-1092, 64 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Dextrose (Other)

Part 4, MK-1092, 64 nmol/kg

Experimental

MK-1092, 64 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Insulin (Biological)

Part 4, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Glargine 3.0 nmol/kg (Drug)

Part 4, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Placebo to MK-1092 (Drug)

Part 4, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Dextrose (Other)

Part 4, Glargine, 3.0 nmol/kg

Active Comparator

Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T2DM

干预措施: Insulin (Biological)

结局指标

主要结局

Number of Participants Who Discontinued the Study Due to an AE

时间窗: Up to 58 days

An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Adverse events that occurred beyond 14 days of dosing were considered Post-Trial AEs. Given the half-life of MK-1092 and glargine, any events observed beyond 14 days would not be considered a result of study drug and were therefore presented together.

GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 1 Diabetes Mellitus (T1DM) (Part 3)

时间窗: Up to approximately 24 hours post-dose

The GIRmax required to maintain blood glucose at each participants' individual clamp target, following administration of MK-1092 SC or glargine SC was determined by use of a continuous glucose infusion during the euglycemic clamp so that glucose levels remained in the euglycemic range and hypoglycemia was prevented. Blood glucose was monitored frequently (\~every 5 minutes), allowing rapid changes to the rate of glucose infusion. Mean and 95% CI were based on a linear fixed effects model containing a fixed effect for treatment (MK-1092 Doses, Glargine). In Part 3, 4 participants (across 2 dosing panels) received glargine. These 4 participants were analyzed together given the small numbers and the same treatment (same dose of glargine) received.

Number of Participants Who Experienced an Adverse Event (AE)

时间窗: Up to 112 days

次要结局

GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1)(Up to approximately 24 hours post-dose)
Rate of Plasma Drug Removal (CL/F) MK-1092 Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Maximal Plasma Insulin Glargine Concentration (Cmax) Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4)(Up to approximately 24 hours post-dose)
Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1)(Up to approximately 24 hours post-dose)
Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T1DM (Part 3)(Up to approximately 24 hours post-dose)
Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4)(Up to approximately 24 hours post-dose)
Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time to Reach Maximum Plasma Insulin Glargine Concentration (Tmax) Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28) ])
Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time to Reach Maximum Plasma Insulin Glargine Concentration (Tmax) Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time to Reach a 50% Decrease In Plasma Insulin Glargine Concentration (t1/2) Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time to Reach a 50% Decrease In Plasma Insulin Glargine Concentration (t1/2) Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28) ])
Maximal Plasma MK-1092 Concentration (Cmax) Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected and at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Maximal Plasma Insulin Glargine Concentration (Cmax) Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) Insulin Glargine Parts 1 and 3(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))
Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) Insulin Glargine Part 4(-15 min (predose), 10 min, 30 min, 1.0 hr, 1.5 hr, 2.0 hr, 3.0 hr, 4.0 hr, 6.0 hr, 9.0 hr, 12 hr, 18 hr, 24 hr, an additional sample will be collected at the end of the clamp, 2d, 3d, 4d, 5d and 7d after SC dose and at post-trial (Day 14 and Day 28))

研究者

发起方

Merck Sharp & Dohme LLC

申办方类型

Industry

责任方

Sponsor

研究点 (1)

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