Single Ascending Dose Study of MK-1092 in Healthy Participants and in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-1092-001)

NCT ID: NCT03170544

Last Updated: 2019-11-15

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-16

Study Completion Date

2018-11-08

Brief Summary

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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)

Detailed Description

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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.

Conditions

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Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Part 1, MK-1092, 4.0 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 4.0 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Part 1, MK-1092, 8.0 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 8.0 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Part 1, MK-1092, 16 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 16 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Part 1, MK-1092, 32 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 32 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Part 1, MK-1092, 64 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 64 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Part 1, Glargine, 3.0 nmol/kg

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

Group Type ACTIVE_COMPARATOR

Glargine 3.0 nmol/kg

Intervention Type DRUG

Glargine 3.0 nmol/kg, SC, as a single dose

Placebo to MK-1092

Intervention Type DRUG

Placebo to MK-1092, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

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

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

Group Type EXPERIMENTAL

MK-1092, 8.0 nmol/kg

Intervention Type DRUG

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

Lispro 1.2 nmol/kg

Intervention Type DRUG

Lispro (Humalog®), 1.2 nmol/kg, IV infusion SC over 3 hours as a single dose starting \~12 hours after MK-1092 administration.

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Part 3, MK-1092, 8.0 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 8.0 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Insulin

Intervention Type BIOLOGICAL

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Part 3, MK-1092, 32 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 32 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Insulin

Intervention Type BIOLOGICAL

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Part 3, Glargine, 3.0 nmol/kg

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

Group Type ACTIVE_COMPARATOR

Glargine 3.0 nmol/kg

Intervention Type DRUG

Glargine 3.0 nmol/kg, SC, as a single dose

Placebo to MK-1092

Intervention Type DRUG

Placebo to MK-1092, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Insulin

Intervention Type BIOLOGICAL

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Part 4, MK-1092, 32 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 32 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Insulin

Intervention Type BIOLOGICAL

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Part 4, MK-1092, 16 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 16 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Insulin

Intervention Type BIOLOGICAL

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Part 4, MK-1092, 64 nmol/kg

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

Group Type EXPERIMENTAL

MK-1092, 64 nmol/kg

Intervention Type DRUG

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

Placebo to glargine

Intervention Type DRUG

Placebo to glargine, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Insulin

Intervention Type BIOLOGICAL

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Part 4, Glargine, 3.0 nmol/kg

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

Group Type ACTIVE_COMPARATOR

Glargine 3.0 nmol/kg

Intervention Type DRUG

Glargine 3.0 nmol/kg, SC, as a single dose

Placebo to MK-1092

Intervention Type DRUG

Placebo to MK-1092, SC, as a single dose

Dextrose

Intervention Type OTHER

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Insulin

Intervention Type BIOLOGICAL

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Interventions

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MK-1092, 4.0 nmol/kg

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

Intervention Type DRUG

MK-1092, 8.0 nmol/kg

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

Intervention Type DRUG

MK-1092, 16 nmol/kg

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

Intervention Type DRUG

MK-1092, 32 nmol/kg

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

Intervention Type DRUG

MK-1092, 64 nmol/kg

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

Intervention Type DRUG

Glargine 3.0 nmol/kg

Glargine 3.0 nmol/kg, SC, as a single dose

Intervention Type DRUG

Lispro 1.2 nmol/kg

Lispro (Humalog®), 1.2 nmol/kg, IV infusion SC over 3 hours as a single dose starting \~12 hours after MK-1092 administration.

Intervention Type DRUG

Placebo to glargine

Placebo to glargine, SC, as a single dose

Intervention Type DRUG

Placebo to MK-1092

Placebo to MK-1092, SC, as a single dose

Intervention Type DRUG

Dextrose

20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.

Intervention Type OTHER

Insulin

Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Intervention Type BIOLOGICAL

Other Intervention Names

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Humalog® Glucose

Eligibility Criteria

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Inclusion Criteria

All participants

* Be a healthy male, or healthy female participant (excluding diabetes mellitus in Part 3 participants) of non-child bearing potential. A female non-child bearing potential is one who is postmenopausal without menses for at least 1 year or whose status is post hysterectomy, bilateral oophorectomy, or tubal ligation.
* Be judged to be in good health based on medical history, physical exam, vital sign measurements, electrocardiogram (ECG) and laboratory safety tests
* Have adequate venous access to support execution of trial procedures

For Parts 1 and 2 (Healthy adult participants)

* Healthy male and female participants between the ages of 18 and 50 years (inclusive)
* Have a Body Mass Index (BMI) ≥18.5 kg/m\^2 and ≤28.0 kg/m\^2 at screening
* Have fasting blood glucose values at screening must be \<100 mg/dL
* Be a non-smoker and/or has not used nicotine or nicotine-containing products (e.g., nicotine patch) for at least approximately 3 months.

For Part 3 (Adult participants with T1DM):

* Be male, or female of non-childbearing potential between 18 to 60 years of age
* Have a diagnosis of T1DM as defined by standard diagnostic criteria for ≥12 months at time of the pretrial (screening) visit
* Have a BMI ≥18.5 kg/m\^2 and ≤32 kg/m\^2 at screening.
* Be on stable doses of basal insulin over the 2-week period prior to screening and over the 2 weeks prior to dosing
* Have a total daily insulin requirement (basal plus prandial) of ≤1.2 units/kg at screening
* Have a hemoglobin A1C (HbA1c) ≤10% at the screening visit.
* Be a non-smoker or smoker who uses no more than 5 cigarettes or equivalent (e.g., e-cigarettes) per day over the prior 3-month period also may be enrolled (at the discretion of the investigator).
* Have a serum C-peptide concentration ≤0.7 ng/mL with a concurrent plasma glucose \>90 mg/dL at screening or anytime within 24 weeks prior to screening.

For Part 4 (Adult participants with T2DM):

* Diagnosis of T2DM as defined by standard diagnostic criteria for ≥12 months at time of pretrial screening.
* Have a BMI ≥18.5 kg/m2 and ≤35.0 kg/m\^2 at screening. BMI = mass (kg)/height (m)\^2.
* Have a hemoglobin A1C (HbA1c) ≥6.5% and ≤10.0%.
* T2DM participants are not required to have been on insulin. If using insulin as background therapy, subjects should have a total daily insulin requirement of ≤1.2 units/kg, and have been on stable doses of basal insulin over the 2-week period prior to screening and over the 2 weeks prior to dosing.
* Be a non-smoker or smoker who uses no greater than 5 cigarettes or equivalent (e.g., e-cigarettes) daily over the prior 3-month period.

Exclusion Criteria

All participants

* Is mentally or legally incapacitated
* Has a history of clinically significant endocrine (excluding diabetes mellitus in Part 3 participants), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases.
* Has a systolic blood pressure (SBP) ≥140 mm Hg and/or a diastolic blood pressure (DBP) ≥90 mm Hg at screening.
* Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV) at screening.
* Has a history of cancer (malignancy) Exceptions: (1) Participants with adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix may participate in the trial; (2) Participants with other malignancies which have been successfully treated ≥10 years prior to the pretrial (screening) visit
* Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic allergic reaction) to prescription or non-prescription drugs or food.
* Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
* Has participated in another investigational trial within 4 weeks.
* Has been randomized to, and received MK-5160 in prior clinical studies.
* Has a QTcF interval \>450 msec, has a history of risk factors for Torsades de Pointes (e.g., heart failure/cardiomyopathy or family history of Long QT Syndrome).
* Has uncorrected hypokalemia
* Has uncorrected hypomagnesemia
* Is taking concomitant medications that prolong the QT/QTc interval.
* 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 post-trial visit.
* Has had a vaccination within 12 weeks of the pretrial visit.
* Consumes greater than 3 glasses of alcoholic beverages per day.
* Consumes excessive amounts, defined as greater than 6 servings 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 6 months
* Has used systemic (intravenous, oral, inhaled) glucocorticoids within 3 months of screening or is anticipated to require treatment with systemic glucocorticoids during study participation.

For Part 1 and Part 2 (Healthy Adult Participants)

\- Has an estimated creatinine clearance of \<90 mL/min based on Cockcroft-Gault equation

For Part 3 (Adult participants with T1DM):

* Has a history of diabetic ketoacidosis in the last 6 months prior to screening.
* Has an estimated creatinine clearance of \<60 mL/min based on the Cockcroft-Gault equation at screening
* Has the diagnosis of hypoglycemia unawareness, or has had one or more severe hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness within 6 months prior to dosing.
* Has other major medical problems requiring medication (i.e., history of myocardial infarction (MI), hypercholesterolemia).
* Has a known history of celiac disease or significant food allergy, at the discretion of the investigator and Sponsor.
* Has a history of hypersensitivity to pharmacologic insulins or to any of the inactive ingredients in recombinant human insulin, or to any E.coli-derived drug product.

For Part 4 (Adult participants with T2DM):

* Participant has an estimated creatinine clearance of \<60 mL/min based on the Cockcroft-Gault equation.
* Has a history of diabetic ketoacidosis in the last 6 months prior to screening.
* Has the diagnosis of hypoglycemia unawareness, or has had one or more severe hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness within 6 months prior to dosing.
* Has a known history of celiac disease or significant food allergy, at the discretion of the Investigator and Sponsor.
* Has been treated with a thiazolidinedione or injectable non-insulin anti-diabetic therapy within the past three months prior to dosing.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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ProSciento Inc. ( Site 0001)

Chula Vista, California, United States

Site Status

Countries

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United States

References

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Walford GA, Duncan KE, Hernandez M, Vaddady P, Hompesch M, Morrow L, Stoch SA. A Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Insulin Dimer. Clin Pharmacol Ther. 2022 Jul;112(1):125-132. doi: 10.1002/cpt.2607. Epub 2022 May 3.

Reference Type DERIVED
PMID: 35390172 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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MK-1092-001

Identifier Type: OTHER

Identifier Source: secondary_id

1092-001

Identifier Type: -

Identifier Source: org_study_id

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