Type 1 Diabetes MellitusPhase 1NCT03170544

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

A Phase 1 study testing MK-1092, 4.0 nmol/kg, MK-1092, 8.0 nmol/kg and MK-1092, 16 nmol/kg in people with Type 1 Diabetes Mellitus and Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
What is being tested?: MK-1092, 4.0 nmol/kg, MK-1092, 8.0 nmol/kg and MK-1092, 16 nmol/kg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 69 participants
Where: 1 siteUnited States
Study dates: 16 Aug 2017to 8 Nov 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Subject 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.

Subject 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

ProSciento Inc. ( Site 0001)
Chula Vista, California, 91911

Other trials in United States

About this study

Official title: 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.

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)

Read the detailed description

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: Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Being tested: MK-1092, 4.0 nmol/kg, MK-1092, 8.0 nmol/kg, MK-1092, 16 nmol/kg, MK-1092, 32 nmol/kg, MK-1092, 64 nmol/kg
Medical subject headings: Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-1092, 4.0 nmol/kgDrug
MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 8.0 nmol/kgDrug
MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 16 nmol/kgDrug
MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 32 nmol/kgDrug
MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
MK-1092, 64 nmol/kgDrug
MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
Glargine 3.0 nmol/kgDrug
Glargine 3.0 nmol/kg, SC, as a single dose
Lispro 1.2 nmol/kgDrug
Also called Humalog®
Lispro (Humalog®), 1.2 nmol/kg, IV infusion SC over 3 hours as a single dose starting ~12 hours after MK-1092 administration.
Placebo to glargineDrug
Placebo to glargine, SC, as a single dose
Placebo to MK-1092Drug
Placebo to MK-1092, SC, as a single dose
DextroseOther
Also called Glucose
20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.
InsulinBiological
Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.

Study groups in NCT03170544
Study group	Role	What they receive
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 Receives: Drug: MK-1092, 4.0 nmol/kg; Drug: Placebo to glargine; Other: Dextrose
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 Receives: Drug: MK-1092, 8.0 nmol/kg; Drug: Placebo to glargine; Other: Dextrose
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 Receives: Drug: MK-1092, 16 nmol/kg; Drug: Placebo to glargine; Other: Dextrose
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 Receives: Drug: MK-1092, 32 nmol/kg; Drug: Placebo to glargine; Other: Dextrose
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 Receives: Drug: MK-1092, 64 nmol/kg; Drug: Placebo to glargine; Other: Dextrose
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 Receives: Drug: Glargine 3.0 nmol/kg; Drug: Placebo to MK-1092; Other: Dextrose
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 Receives: Drug: MK-1092, 8.0 nmol/kg; Drug: Lispro 1.2 nmol/kg; Other: Dextrose
Part 3, MK-1092, 8.0 nmol/kg	Experimental	MK-1092, (8.0 nmol/kg based on Part 1), SC, in participants with T1DM. Receives: Drug: MK-1092, 8.0 nmol/kg; Drug: Placebo to glargine; Other: Dextrose; Biological: Insulin
Part 3, MK-1092, 32 nmol/kg	Experimental	MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T1DM Receives: Drug: MK-1092, 32 nmol/kg; Drug: Placebo to glargine; Other: Dextrose; Biological: Insulin
Part 3, Glargine, 3.0 nmol/kg	Active comparator	Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T1DM Receives: Drug: Glargine 3.0 nmol/kg; Drug: Placebo to MK-1092; Other: Dextrose; Biological: Insulin
Part 4, MK-1092, 32 nmol/kg	Experimental	MK-1092, 32 nmol/kg, SC, as a single dose, in participants with T2DM Receives: Drug: MK-1092, 32 nmol/kg; Drug: Placebo to glargine; Other: Dextrose; Biological: Insulin
Part 4, MK-1092, 16 nmol/kg	Experimental	MK-1092, 16 nmol/kg, SC, as a single dose, in participants with T2DM Receives: Drug: MK-1092, 16 nmol/kg; Drug: Placebo to glargine; Other: Dextrose; Biological: Insulin
Part 4, MK-1092, 64 nmol/kg	Experimental	MK-1092, 64 nmol/kg, SC, as a single dose, in participants with T2DM Receives: Drug: MK-1092, 64 nmol/kg; Drug: Placebo to glargine; Other: Dextrose; Biological: Insulin
Part 4, Glargine, 3.0 nmol/kg	Active comparator	Glargine, 3.0 nmol/kg, SC, as a single dose, in participants with T2DM Receives: Drug: Glargine 3.0 nmol/kg; Drug: Placebo to MK-1092; Other: Dextrose; Biological: Insulin

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Who Experienced an Adverse Event (AE)
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.
Measured: Up to 112 days
Number of Participants Who Discontinued the Study Due to an AE
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.
Measured: Up to 58 days
GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 1 Diabetes Mellitus (T1DM) (Part 3)
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.
Measured: Up to approximately 24 hours post-dose

Secondary outcomes (23)

GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1)
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 1, 10 participants (across 5 dosing panels) received glargine. These 10 participants in Part 1 were analyzed together given the small numbers and same treatment (same dose of glargine) received.
Measured: Up to approximately 24 hours post-dose
GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4)
The GIRmax, 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. For Part 4, a linear mixed effects model containing a fixed effect for treatment (MK-1092, Glargine), a nested effect from participants within treatment, an interaction between treatment and period (treatment by period: Period = Period 1, 2, 3) and a random effect due to participants was used. MK-1092 was administered to a single cohort of participants in Periods 1, 2, and 3. Glargine was administered to a single cohort of participants as 3.0 nmol/kg SC in Periods 1, 2, and 3.
Measured: 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 Healthy Adult Participants (Part 1)
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 in Part 1 only. TWA(GIR)= Time-weighted average based on GIR values calculated as AUC (area under the curve) based on GIR values observed from time zero to t divided by t, t= 24 hours. Mean and 95% CI are based on a linear fixed effects model containing a fixed effect for treatment (MK-1092 Doses, Glargine). In Part 1, 10 participants (across 5 dosing panels) received glargine. These 10 participants in Part 1 were analyzed together given the small numbers and same treatment (same dose of glargine) received.
Measured: 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)
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 in Part 3 only. TWA(GIR)= Time-weighted average based on GIR values calculated as AUC (area under the curve) based on GIR values observed from time zero to t divided by t, t= 24 hours. Mean and 95% CI are 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 same treatment (same dose of glargine) received.
Measured: 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)
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 in Part 4 only. TWA(GIR)= Time-weighted average based on GIR values calculated as AUC (area under the curve) based on GIR values observed from time zero to t divided by t, t= 24 hours. Mean and 95% CI were based on a linear mixed effects model containing a fixed effect for treatment (MK, Glargine), period (Period 1, Period 2 and Period 3), a nested effect from participants within treatment, and interaction between treatment and period. MK-1092 or glargine was administered to a single cohort of participants in Periods 1, 2, and 3.
Measured: Up to approximately 24 hours post-dose
Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given in Parts 1 and 3 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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 Parts 1 and 3
AUC0-inf is a measure of the total concentration levels of drug in the plasma after the dose is given in Parts 1 and 3 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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
CL/F is the rate at which a drug is removed from the body via renal, hepatic, and other clearance pathways after the dose is given in Parts 1 and 3 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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
Tmax is the amount of the time to reach the maximum concentration in the plasma after the drug dose is given in Parts 1 and 3 only.
Measured: -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
t1/2 is the time required for a given drug concentration in the plasma to decrease by 50% after the drug dose is given in Parts 1 and 3 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given in Parts 4 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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
AUC0-inf is a measure of the total concentration levels of drug in the plasma after the dose is given in Part 4 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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 Part 4
CL/F is the rate at which a drug is removed from the body via renal, hepatic, and other clearance pathways after the dose is given in Part 4 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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
Tmax is the amount of the time to reach the maximum concentration in the plasma after the drug dose is given in Part 4 only.
Measured: -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) Part 4
t1/2 is the time required for a given drug concentration in the plasma to decrease by 50% after the drug dose is given in Part 4 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given in Parts 1 and 3 only. Healthy participants received glargine in Panel A-E, and participants with T1DM received glargine in Panel G and H. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation. In Part 1, 9 participants (across 5 dosing panels) received glargine and had quantifiable glargine levels, and, in Part 3, 4 participants (across 2 dosing panels) received glargine and had quantifiable glargine levels. These 9 participants in Part 1 were analyzed together and these 4 participants in Part 3 were analyzed together given the small numbers and same treatment (same dose of glargine) received.
Measured: -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
AUC0-inf is a measure of the total concentration levels of drug in the plasma after the dose is given in Parts 1 and 3 only. Healthy participants received glargine in Panel A-E, and participants with T1DM received glargine in Panel G and H. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation. In Part 1, 8 participants (across 5 dosing panels) received glargine and had sufficient terminal phase data, and, in Part 3, 3 participants (across 2 dosing panels) received glargine and had sufficient terminal phase data. These 8 participants in Part 1 were analyzed together and these 3 participants in Part 3 were analyzed together given the small numbers and same treatment (same dose of glargine) received.
Measured: -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 Insulin Glargine Concentration (Tmax) Parts 1 and 3
Tmax is the amount of the time to reach the maximum concentration in the plasma after the drug dose is given in Parts 1 and 3 only. Healthy participants received glargine in Panel A-E, and participants with T1DM received glargine in Panel G and H. In Part 1, 9 participants (across 5 dosing panels) received glargine and had quantifiable glargine levels, and, in Part 3, 4 participants (across 2 dosing panels) received glargine and had quantifiable glargine levels. These 9 participants in Part 1 were analyzed together and these 4 participants in Part 3 were analyzed together given the small numbers and same treatment (same dose of glargine) received.
Measured: -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
t1/2 is the time required for a given drug concentration in the plasma to decrease by 50% after the drug dose is given in Parts 1 and 3 only. Healthy participants received glargine in Panel A-E, and participants with T1DM received glargine in Panel G and H. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation. In Part 1, 8 participants (across 5 dosing panels) received glargine and had sufficient terminal phase data, and, in Part 3, 3 participants (across 2 dosing panels) received glargine and sufficient terminal phase data. These 8 participants in Part 1 were analyzed together and these 3 participants in Part 3 were analyzed together given the small numbers and same treatment (same dose of glargine) received.
Measured: -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) Part 4
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given in Parts 4 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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
AUC0-inf is a measure of the total concentration levels of drug in the plasma after the dose is given in Part 4 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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 Insulin Glargine Concentration (Tmax) Part 4
Tmax is the amount of the time to reach the maximum concentration in the plasma after the drug dose is given in Part 4 only.
Measured: -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
t1/2 is the time required for a given drug concentration in the plasma to decrease by 50% after the drug dose is given in Part 4 only. The method of dispersion referenced below of geometric coefficient of variation is actually percent geometric coefficient of variation.
Measured: -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) ]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Aug 20178 Nov 2018

First posted31 May 2017
Study start16 Aug 2017
Primary completion8 Nov 2018
Study completion8 Nov 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03170544
Sponsor's protocol ID: 1092-001
Other IDs: MK-1092-001
Status last verified: Nov 2019
First submitted: 26 May 2017
Last updated: 15 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 35390172

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Study at a glance

From the registry record, last updated by the sponsor on 15 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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.
ClinicalTrials.gov ID: NCT03170544
Acronym / sponsor ID: 1092-001
Conditions: Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 16 Aug 2017 (actual)
Primary completion: 8 Nov 2018 (actual)
Study completion: 8 Nov 2018 (actual)
First posted: 31 May 2017 (actual)
Results: Posted 15 Nov 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 14

Arm	Type	Receives
Part 1, MK-1092, 4.0 nmol/kg	Experimental	Drug: MK-1092, 4.0 nmol/kg, Drug: Placebo to glargine, Other: DextroseMK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 8.0 nmol/kg	Experimental	Drug: MK-1092, 8.0 nmol/kg, Drug: Placebo to glargine, Other: DextroseMK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 16 nmol/kg	Experimental	Drug: MK-1092, 16 nmol/kg, Drug: Placebo to glargine, Other: DextroseMK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 32 nmol/kg	Experimental	Drug: MK-1092, 32 nmol/kg, Drug: Placebo to glargine, Other: DextroseMK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, MK-1092, 64 nmol/kg	Experimental	Drug: MK-1092, 64 nmol/kg, Drug: Placebo to glargine, Other: DextroseMK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 1, Glargine, 3.0 nmol/kg	Active comparator	Drug: Glargine 3.0 nmol/kg, Drug: Placebo to MK-1092, Other: DextroseGlargine, 3.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants
Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg	Experimental	Drug: MK-1092, 8.0 nmol/kg, Drug: Lispro 1.2 nmol/kg, Other: DextroseMK-1092, 8.0 nmol/kg dose selection based on Part 1 + lispro (Humalog®), 1.2 nmol/kg, as a single dose, in healthy participants
Part 3, MK-1092, 8.0 nmol/kg	Experimental	Drug: MK-1092, 8.0 nmol/kg, Drug: Placebo to glargine, Other: Dextrose, Biological: InsulinMK-1092, (8.0 nmol/kg based on Part 1), SC, in participants with T1DM.
Part 3, MK-1092, 32 nmol/kg	Experimental	Drug: MK-1092, 32 nmol/kg, Drug: Placebo to glargine, Other: Dextrose, Biological: InsulinMK-1092, 32 nmol/kg, SC, as a single dose, in participants with T1DM
Part 3, Glargine, 3.0 nmol/kg	Active comparator	Drug: Glargine 3.0 nmol/kg, Drug: Placebo to MK-1092, Other: Dextrose, Biological: InsulinGlargine, 3.0 nmol/kg, SC, as a single dose, in participants with T1DM
Part 4, MK-1092, 32 nmol/kg	Experimental	Drug: MK-1092, 32 nmol/kg, Drug: Placebo to glargine, Other: Dextrose, Biological: InsulinMK-1092, 32 nmol/kg, SC, as a single dose, in participants with T2DM
Part 4, MK-1092, 16 nmol/kg	Experimental	Drug: MK-1092, 16 nmol/kg, Drug: Placebo to glargine, Other: Dextrose, Biological: InsulinMK-1092, 16 nmol/kg, SC, as a single dose, in participants with T2DM
Part 4, MK-1092, 64 nmol/kg	Experimental	Drug: MK-1092, 64 nmol/kg, Drug: Placebo to glargine, Other: Dextrose, Biological: InsulinMK-1092, 64 nmol/kg, SC, as a single dose, in participants with T2DM
Part 4, Glargine, 3.0 nmol/kg	Active comparator	Drug: Glargine 3.0 nmol/kg, Drug: Placebo to MK-1092, Other: Dextrose, Biological: InsulinGlargine, 3.0 nmol/kg, SC, as a single dose, in participants with T2DM

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-1092, 4.0 nmol/kgMK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants	Drug	Part 1, MK-1092, 4.0 nmol/kg
MK-1092, 8.0 nmol/kgMK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants	Drug	Part 1, MK-1092, 8.0 nmol/kg, Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg, Part 3, MK-1092, 8.0 nmol/kg
MK-1092, 16 nmol/kgMK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants	Drug	Part 1, MK-1092, 16 nmol/kg, Part 4, MK-1092, 16 nmol/kg
MK-1092, 32 nmol/kgMK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants	Drug	Part 1, MK-1092, 32 nmol/kg, Part 3, MK-1092, 32 nmol/kg, Part 4, MK-1092, 32 nmol/kg
MK-1092, 64 nmol/kgMK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants	Drug	Part 1, MK-1092, 64 nmol/kg, Part 4, MK-1092, 64 nmol/kg
Glargine 3.0 nmol/kgGlargine 3.0 nmol/kg, SC, as a single dose	Drug	Part 1, Glargine, 3.0 nmol/kg, Part 3, Glargine, 3.0 nmol/kg, Part 4, Glargine, 3.0 nmol/kg
Lispro 1.2 nmol/kgAlso: Humalog®Lispro (Humalog®), 1.2 nmol/kg, IV infusion SC over 3 hours as a single dose starting ~12 hours after MK-1092 administration.	Drug	Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg
Placebo to glarginePlacebo to glargine, SC, as a single dose	Drug	Part 1, MK-1092, 16 nmol/kg, Part 1, MK-1092, 32 nmol/kg, Part 1, MK-1092, 4.0 nmol/kg, Part 1, MK-1092, 64 nmol/kg, Part 1, MK-1092, 8.0 nmol/kg, Part 3, MK-1092, 32 nmol/kg, Part 3, MK-1092, 8.0 nmol/kg, Part 4, MK-1092, 16 nmol/kg, Part 4, MK-1092, 32 nmol/kg, Part 4, MK-1092, 64 nmol/kg
Placebo to MK-1092Placebo to MK-1092, SC, as a single dose	Drug	Part 1, Glargine, 3.0 nmol/kg, Part 3, Glargine, 3.0 nmol/kg, Part 4, Glargine, 3.0 nmol/kg
DextroseAlso: Glucose20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.	Other	Part 1, Glargine, 3.0 nmol/kg, Part 1, MK-1092, 16 nmol/kg, Part 1, MK-1092, 32 nmol/kg, Part 1, MK-1092, 4.0 nmol/kg, Part 1, MK-1092, 64 nmol/kg, Part 1, MK-1092, 8.0 nmol/kg, Part 2, MK-1092, 8.0 nmol/kg + lispro, 1.2 nmol/kg, Part 3, Glargine, 3.0 nmol/kg, Part 3, MK-1092, 32 nmol/kg, Part 3, MK-1092, 8.0 nmol/kg, Part 4, Glargine, 3.0 nmol/kg, Part 4, MK-1092, 16 nmol/kg, Part 4, MK-1092, 32 nmol/kg, Part 4, MK-1092, 64 nmol/kg
InsulinParticipants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.	Biological	Part 3, Glargine, 3.0 nmol/kg, Part 3, MK-1092, 32 nmol/kg, Part 3, MK-1092, 8.0 nmol/kg, Part 4, Glargine, 3.0 nmol/kg, Part 4, MK-1092, 16 nmol/kg, Part 4, MK-1092, 32 nmol/kg, Part 4, MK-1092, 64 nmol/kg

Primary outcome

Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to 112 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.
Number of Participants Who Discontinued the Study Due to an AE
Time frame: 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)
Time frame: 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.

23 secondary outcomes

GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1)
Time frame: Up to approximately 24 hours post-dose
GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4)
Time frame: 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 Healthy Adult Participants (Part 1)
Time frame: 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)
Time frame: 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)
Time frame: Up to approximately 24 hours post-dose
Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3
Time frame: -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 Parts 1 and 3
Time frame: -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
Time frame: -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
Time frame: -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
Time frame: -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
Time frame: -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
Time frame: -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 Part 4
Time frame: -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
Time frame: -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) Part 4
Time frame: -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
Time frame: -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
Time frame: -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 Insulin Glargine Concentration (Tmax) Parts 1 and 3
Time frame: -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
Time frame: -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) Part 4
Time frame: -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
Time frame: -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 Insulin Glargine Concentration (Tmax) Part 4
Time frame: -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
Time frame: -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) ]

Results and safety

Results posted to the registry on 15 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg	10	9
Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg	6	6
Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg	6	6
Part 1 (Healthy Adults) MK-1092 16 Nmol/kg	7	6
Part 1 (Healthy Adults) MK-1092 32 Nmol/kg	6	6
Part 1 (Healthy Adults) MK-1092 64 Nmol/kg	6	6
Part 2 (Healthy Adults) MK-1092 + Insulin Lipro	0	0
Part 3 (T1DM) Glargine 3.0 Nmol/kg	0	0
Part 3 (T1DM) MK-1092 8.0 Nmol/kg	0	0
Part 3 (T1DM) MK-1092 32 Nmol/kg	0	0
Part 4 (T2DM) Glargine	0	0
Part 4 (T2DM) MK-1092	0	0

Primary outcome: Number of Participants Who Experienced an Adverse Event (AE)

Time frame: Up to 112 days. Count of participants. Unit: Participants

Measure	Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg n = 10	Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 16 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 32 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 64 Nmol/kg n = 6	Part 1 (Healthy Adults) Post-trial n = 40	Part 2 (Healthy Adults) MK-1092 + Insulin Lipro n = 4	Part 2 (Healthy Adults) MK-1092 + Insulin Lipro Post-Trial n = 4	Part 3 (T1DM) Glargine 3.0 Nmol/kg n = 4	Part 3 (T1DM) MK-1092 8.0 Nmol/kg n = 6	Part 3 (T1DM) MK-1092 32 Nmol/kg n = 6	Part 3 (T1DM) Post-Trial n = 16	Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 1) n = 3	Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 2) n = 3	Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 3) n = 3	Part 4 (T2DM) MK-1092 32 Nmol/kg (Period 1) n = 6	Part 4 (T2DM) MK-1092 16 Nmol/kg (Period 2) n = 6	Part 4, (T2DM) MK-1092 64 Nmol/kg (Period 3) n = 6	Part 4 (T2DM) Post-Trial n = 9
Value	1	1	4	3	3	2	0	3	1	2	6	5	2	3	1	0	3	3	4	0

Population analysed: The analysis population included all participants who received at least one dose of the investigational drug. Post-trial adverse events were pooled across treatment groups in each part of the study.

Primary outcome: Number of Participants Who Discontinued the Study Due to an AE

Time frame: Up to 58 days. Count of participants. Unit: Participants

Measure	Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg n = 10	Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 16 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 32 Nmol/kg n = 6	Part 1 (Healthy Adults) MK-1092 64 Nmol/kg n = 6	Part 1 (Healthy Adults) Post-trial n = 40	Part 2 (Healthy Adults) MK-1092 + Insulin Lipro n = 4	Part 2 (Healthy Adults) MK-1092 + Insulin Lipro Post-Trial n = 4	Part 3 (T1DM) Glargine 3.0 Nmol/kg n = 4	Part 3 (T1DM) MK-1092 8.0 Nmol/kg n = 6	Part 3 (T1DM) MK-1092 32 Nmol/kg n = 6	Part 3 (T1DM) Post-Trial n = 16	Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 1) n = 3	Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 2) n = 3	Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 3) n = 3	Part 4 (T2DM) MK-1092 32 Nmol/kg (Period 1) n = 6	Part 4 (T2DM) MK-1092 16 Nmol/kg (Period 2) n = 6	Part 4, (T2DM) MK-1092 64 Nmol/kg (Period 3) n = 6	Part 4 (T2DM) Post-Trial n = 9
Value	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

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

Time frame: Up to approximately 24 hours post-dose. Mean (95% Confidence Interval). Unit: mg/kg/min

Measure	Part 3 (T1DM) MK-1092 8.0 Nmol/kg n = 6	Part 3 (T1DM) MK-1092 32 Nmol/kg n = 6	Part 3 (T1DM) Glargine 3.0 Nmol/kg n = 4
Value	1.33 (0.63 to 2.04)	2.74 (2.03 to 3.44)	2.32 (1.45 to 3.18)

Part 3 (T1DM) MK-1092 8.0 Nmol/kg: Mean: 1.33 (95% CI 0.63 to 2.04)
Part 3 (T1DM) MK-1092 32 Nmol/kg: Mean: 2.74 (95% CI 2.03 to 3.44)

Population analysed: The analysis population included participants in Part 3 who complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations. The glargine-treated group was pooled; n=2 participants per panel.

23 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 112 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 1 (Healthy Adults) MK-1092 16 Nmol/kg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1 (Healthy Adults) MK-1092 32 Nmol/kg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1 (Healthy Adults) MK-1092 64 Nmol/kg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 1 (Healthy Adults) Post-trial	0 of 40 (0%)	0 of 40 (0%)	0 of 40
Part 2 (Healthy Adults) MK-1092 + Insulin Lipro	0 of 4 (0%)	3 of 4 (75%)	0 of 4
Part 2 (Healthy Adults) MK-1092 + Insulin Lipro Post-trial	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Part 3 (T1DM) Glargine 3.0 Nmol/kg	0 of 4 (0%)	2 of 4 (50%)	0 of 4
Part 3 (T1DM) MK-1092 8.0 Nmol/kg	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Part 3 (T1DM) MK-1092 32 Nmol/kg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part 3 (T1DM) Post-trial	0 of 16 (0%)	2 of 16 (12.5%)	0 of 16
Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 1)	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 2)	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3
Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 3)	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Part 4 (T2DM) MK-1092 32 Nmol/kg (Period 1)	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 4 (T2DM) MK-1092 16 Nmol/kg (Period 2)	0 of 6 (0%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35390172Walford 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.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced an Adverse Event (AE) (time frame: Up to 112 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03170544, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2019.