Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Conditions
Brief summary
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
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.
Interventions
DRUGMK-1092, 4.0 nmol/kg
MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
DRUGMK-1092, 8.0 nmol/kg
MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
DRUGMK-1092, 16 nmol/kg
MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
DRUGMK-1092, 32 nmol/kg
MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
DRUGMK-1092, 64 nmol/kg
MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants
DRUGGlargine 3.0 nmol/kg
Glargine 3.0 nmol/kg, SC, as a single dose
DRUGLispro 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.
Placebo to glargine, SC, as a single dose
DRUGPlacebo to MK-1092
Placebo to MK-1092, SC, as a single dose
OTHERDextrose
20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.
BIOLOGICALInsulin
Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | 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 | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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 | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) | 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. |
| 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) ] | 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. |
| 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) ] | 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. |
| 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) | 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. |
| 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 | 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. |
| 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 | 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. |
Countries
United States
Participant flow
Recruitment details
This was a 4-part study, participants received MK-1092 or glargine: Part 1 - healthy adult participants; Part 2, healthy adult participants received MK-1092 and also insulin lispro (Humalog®); Part 3 - adult participants with Type 1 diabetes mellitus; Part 4 had 3 periods (Periods 1, 2, and 3), participants with Type 2 diabetes mellitus.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg Glargine, 3.0 nmol/kg, SC, as a single dose under the euglycemic clamp in healthy participants | 10 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp in healthy participants | 6 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp in healthy participants | 6 |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in healthy participants | 6 |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp in healthy participants | 6 |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp in healthy participants | 6 |
| Part 2 (Healthy Adults) MK-1092 + Insulin Lipro Humalog MK-1092 8 nmol/kg SC+ Insulin Lipro (Humalog®) 1.2 nmol/kg IV, as a single dose under the euglycemic clamp in healthy participants | 4 |
| Part 3 (T1DM) Glargine 3.0 Nmol/kg Glargine, 3.0 nmol/kg, SC, as a single dose under the euglycemic clamp in participants with T1DM | 4 |
| Part 3 (T1DM) MK-1092 8.0 Nmol/kg MK-1092 8 nmol/kg, SC, as a single dose under the euglycemic clamp in participants with T1DM | 6 |
| Part 3 (T1DM) MK-1092 32 Nmol/kg MK-1092 32 nmol/kg, SC, as a single dose under the euglycemic clamp in participants with T1DM | 6 |
| Part 4 (T2DM) Glargine Glargine, SC, 3.0 nmol/kg, as a single dose in Periods 1, 2, and 3 under the euglycemic clamp in participants with T2DM | 3 |
| Part 4 (T2DM) MK-1092 MK-1092, SC, 32-, 16-, and 64 nmol/kg in Periods 1, 2, and 3, respectively, as a single dose under the euglycemic clamp in participants with T2DM | 6 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1 | Not treated | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Part 2 (Healthy Adults) MK-1092 + Insulin Lipro Humalog | Part 3 (T1DM) Glargine 3.0 Nmol/kg | Part 3 (T1DM) MK-1092 8.0 Nmol/kg | Part 3 (T1DM) MK-1092 32 Nmol/kg | Part 4 (T2DM) Glargine | Part 4 (T2DM) MK-1092 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.3 Years STANDARD_DEVIATION 8.5 | 37.5 Years STANDARD_DEVIATION 12 | 33.5 Years STANDARD_DEVIATION 9.1 | 34.2 Years STANDARD_DEVIATION 8.7 | 35.2 Years STANDARD_DEVIATION 9.3 | 35.0 Years STANDARD_DEVIATION 5.7 | 45.3 Years STANDARD_DEVIATION 2.6 | 39.0 Years STANDARD_DEVIATION 12 | 34.2 Years STANDARD_DEVIATION 10 | 40.0 Years STANDARD_DEVIATION 10.4 | 52.0 Years STANDARD_DEVIATION 9.6 | 51.5 Years STANDARD_DEVIATION 4.3 | 38.3 Years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 5 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 3 Participants | 4 Participants | 3 Participants | 6 Participants | 5 Participants | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 0 Participants | 1 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 6 Participants | 4 Participants | 3 Participants | 5 Participants | 2 Participants | 4 Participants | 5 Participants | 4 Participants | 3 Participants | 6 Participants | 51 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 4 Participants | 6 Participants | 4 Participants | 2 Participants | 3 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 40 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 16 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 |
| other Total, other adverse events | 1 / 10 | 1 / 6 | 4 / 6 | 3 / 6 | 3 / 6 | 2 / 6 | 0 / 40 | 3 / 4 | 1 / 4 | 2 / 4 | 6 / 6 | 5 / 6 | 2 / 16 | 3 / 3 | 1 / 3 | 0 / 3 | 3 / 6 | 3 / 6 | 4 / 6 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 40 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 16 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 |
Outcome results
Primary
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.
Time frame: Up to approximately 24 hours post-dose
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 1 Diabetes Mellitus (T1DM) (Part 3) | 1.33 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 1 Diabetes Mellitus (T1DM) (Part 3) | 2.74 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 1 Diabetes Mellitus (T1DM) (Part 3) | 2.32 mg/kg/min |
95% CI: [0.63, 2.04]
95% CI: [2.03, 3.44]
Primary
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.
Time frame: Up to 58 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 1 (Healthy Adults) Post-trial | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 2 (Healthy Adults) MK-1092 + Insulin Lipro | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 2 (Healthy Adults) MK-1092 + Insulin Lipro Post-Trial | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 3 (T1DM) Glargine 3.0 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 3 (T1DM) MK-1092 8.0 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 3 (T1DM) MK-1092 32 Nmol/kg | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 3 (T1DM) Post-Trial | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 1) | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 2) | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 3) | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 4 (T2DM) MK-1092 32 Nmol/kg (Period 1) | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 4 (T2DM) MK-1092 16 Nmol/kg (Period 2) | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 4, (T2DM) MK-1092 64 Nmol/kg (Period 3) | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
| Part 4 (T2DM) Post-Trial | Number of Participants Who Discontinued the Study Due to an AE | 0 Participants |
Primary
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.
Time frame: Up to 112 days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Part 1 (Healthy Adults) Post-trial | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
| Part 2 (Healthy Adults) MK-1092 + Insulin Lipro | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 2 (Healthy Adults) MK-1092 + Insulin Lipro Post-Trial | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |
| Part 3 (T1DM) Glargine 3.0 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Part 3 (T1DM) MK-1092 8.0 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| Part 3 (T1DM) MK-1092 32 Nmol/kg | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Part 3 (T1DM) Post-Trial | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 1) | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 2) | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |
| Part 4 (T2DM) Glargine 3.0 Nmol/kg (Period 3) | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
| Part 4 (T2DM) MK-1092 32 Nmol/kg (Period 1) | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 4 (T2DM) MK-1092 16 Nmol/kg (Period 2) | Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 4, (T2DM) MK-1092 64 Nmol/kg (Period 3) | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
| Part 4 (T2DM) Post-Trial | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
Secondary
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.
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)
Population: The analysis population included participants in Part 4 who received glargine and complied with the protocol (exposure to treatment, availability of measurements, major protocol deviations) so that data exhibited effects of treatment. Five participants (Period 1:1; Period 2:2; Period 3:2) were excluded due to insufficient terminal phase data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) Insulin Glargine Part 4 | 4960 hr*pg/mL | Geometric Coefficient of Variation 66.2 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) Insulin Glargine Part 4 | 928 hr*pg/mL | — |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) Insulin Glargine Part 4 | 8020 hr*pg/mL | — |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 and 3 who received glargine and complied with the protocol sufficiently so that the data exhibited the effects of treatment. Two participants in Part 1 and 1 in Part 3 were excluded due to insufficient terminal phase data. Data across panels were pooled for Parts 1 and 3.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) Insulin Glargine Parts 1 and 3 | 3180 hr*pg/mL | Geometric Coefficient of Variation 44.7 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) Insulin Glargine Parts 1 and 3 | 4240 hr*pg/mL | Geometric Coefficient of Variation 93.9 |
Secondary
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.
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)
Population: The analysis population included participants in Part 4 who received MK-1092 and complied with the protocol (exposure to treatment, measurement availability, major protocol deviations) so that data exhibited effects of treatment. Seven participants (Period 1:1; Period 2:3; Period 3:3) were excluded due to insufficient terminal phase data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Part 4 | 46.1 nM*hr | Geometric Coefficient of Variation 34.4 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Part 4 | 32.7 nM*hr | Geometric Coefficient of Variation 48.8 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Part 4 | 111 nM*hr | Geometric Coefficient of Variation 20.7 |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 \& 3 who received MK-1092 and complied with the protocol (exposure to treatment, availability of measurements, absence of major protocol deviations) so that data exhibited effects of treatment. For the MK-1092 4.0 nmol/kg group, 5 participants were excluded (insufficient terminal phase data).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3 | 10.6 nM*hr | — |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3 | 17.2 nM*hr | Geometric Coefficient of Variation 12 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3 | 37.5 nM*hr | Geometric Coefficient of Variation 11.5 |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3 | 76.0 nM*hr | Geometric Coefficient of Variation 10.2 |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3 | 161 nM*hr | Geometric Coefficient of Variation 14.1 |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3 | 21.5 nM*hr | Geometric Coefficient of Variation 22.2 |
| Part 1 (Healthy Adults) Post-trial | Area Under the Plasma Drug Curve From 0 to Infinity (AUC0-inf) MK-1092 Parts 1 and 3 | 74.9 nM*hr | Geometric Coefficient of Variation 30.5 |
Secondary
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.
Time frame: Up to approximately 24 hours post-dose
Population: The analysis population included participants in Part 4 who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4) | 1.90 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4) | 1.40 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4) | 2.83 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4) | 0.93 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4) | 1.43 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With Type 2 Diabetes Mellitus (T2DM) (Part 4) | 1.20 mg/kg/min |
Secondary
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.
Time frame: Up to approximately 24 hours post-dose
Population: The analysis population included participants in Part 1 who complied with the protocol sufficiently to ensure that these data likely exhibited 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 0.92 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 1.69 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 3.10 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 3.32 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 4.39 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | GIRmax After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 2.72 mg/kg/min |
Secondary
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.
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)
Population: The analysis population included participants in Part 4 who received glargine and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment, per the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Maximal Plasma Insulin Glargine Concentration (Cmax) Part 4 | 85.6 pg/mL | Geometric Coefficient of Variation 18 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Maximal Plasma Insulin Glargine Concentration (Cmax) Part 4 | 91.9 pg/mL | Geometric Coefficient of Variation 35.1 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Maximal Plasma Insulin Glargine Concentration (Cmax) Part 4 | 105 pg/mL | Geometric Coefficient of Variation 33.9 |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 and 3 who received glargine and complied with the protocol sufficiently so that the data exhibited effects of treatment. One participant (Part 1) was excluded (no quantifiable glargine concentration). Data across panels were pooled for Parts 1 and 3.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Maximal Plasma Insulin Glargine Concentration (Cmax) Parts 1 and 3 | 115 pg/mL | Geometric Coefficient of Variation 48.4 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Maximal Plasma Insulin Glargine Concentration (Cmax) Parts 1 and 3 | 186 pg/mL | Geometric Coefficient of Variation 33.8 |
Secondary
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.
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)
Population: The analysis population included participants in Part 4 who received MK-1092 and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment, per the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Part 4 | 1.72 nM | Geometric Coefficient of Variation 46 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Part 4 | 1.14 nM | Geometric Coefficient of Variation 32.6 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Part 4 | 3.60 nM | Geometric Coefficient of Variation 23 |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 and 3 who received MK-1092 and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment, per the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3 | 0.382 nM | Geometric Coefficient of Variation 21.7 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3 | 0.747 nM | Geometric Coefficient of Variation 25 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3 | 1.63 nM | Geometric Coefficient of Variation 12.7 |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3 | 2.91 nM | Geometric Coefficient of Variation 18.7 |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3 | 6.82 nM | Geometric Coefficient of Variation 27.6 |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3 | 0.788 nM | Geometric Coefficient of Variation 20.4 |
| Part 1 (Healthy Adults) Post-trial | Maximal Plasma MK-1092 Concentration (Cmax) Parts 1 and 3 | 3.43 nM | Geometric Coefficient of Variation 18.4 |
Secondary
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.
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)
Population: The analysis population included participants in Parts 4 who received MK-1092 and complied with the protocol (exposure to treatment, measurement availability, major protocol deviations) so that data exhibited effects of treatment. Seven participants (Period 1:1; Period 2:3; Period 3:3) were excluded due to insufficient terminal phase data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Part 4 | 55.6 L/hr | Geometric Coefficient of Variation 27.4 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Part 4 | 45.9 L/hr | Geometric Coefficient of Variation 52.5 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Part 4 | 40.7 L/hr | Geometric Coefficient of Variation 13.5 |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 \& 3 who received MK-1092 and complied with the protocol (exposure to treatment, availability of measurements, absence of major protocol deviations) so that data exhibited effects of treatment. For the MK-1092 4.0 nmol/kg group, 5 participants were excluded (insufficient terminal phase data).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3 | 25.6 L/hr | — |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3 | 35.0 L/hr | Geometric Coefficient of Variation 13.3 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3 | 33.8 L/hr | Geometric Coefficient of Variation 19.8 |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3 | 32.2 L/hr | Geometric Coefficient of Variation 16.1 |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3 | 31.7 L/hr | Geometric Coefficient of Variation 13.9 |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3 | 33.6 L/hr | Geometric Coefficient of Variation 28.1 |
| Part 1 (Healthy Adults) Post-trial | Rate of Plasma Drug Removal (CL/F) MK-1092 Parts 1 and 3 | 35.9 L/hr | Geometric Coefficient of Variation 26.6 |
Secondary
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.
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) ]
Population: The analysis population included participants in Part 4 who received glargine and complied with the protocol (exposure to treatment, availability of measurements, major protocol deviations) so that data exhibited effects of treatment. Five participants (Period 1:1; Period 2:2; Period 3:2) were excluded due to insufficient terminal phase data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma Insulin Glargine Concentration (t1/2) Part 4 | 45.2 Hours | Geometric Coefficient of Variation 53.2 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma Insulin Glargine Concentration (t1/2) Part 4 | 8.10 Hours | — |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma Insulin Glargine Concentration (t1/2) Part 4 | 46.5 Hours | — |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 and 3 who received glargine and sufficiently complied with the protocol so that the data exhibited the effects of treatment. Two participants excluded in Part 1 and 1 participant excluded in Part 3 due to insufficient terminal phase data. Data across panels were pooled for Parts 1 and 3.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma Insulin Glargine Concentration (t1/2) Parts 1 and 3 | 18.8 Hours | Geometric Coefficient of Variation 64.5 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma Insulin Glargine Concentration (t1/2) Parts 1 and 3 | 15.0 Hours | Geometric Coefficient of Variation 65.8 |
Secondary
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.
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)
Population: The analysis population included participants in Part 4 who received MK-1092 and complied with the protocol (exposure to treatment, measurement availability, major protocol deviations) so that data exhibited effects of treatment. Seven participants (Period 1:1; Period 2:3; Period 3:3) were excluded due to insufficient terminal phase data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Part 4 | 8.26 Hours | Geometric Coefficient of Variation 39.1 |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Part 4 | 9.09 Hours | Geometric Coefficient of Variation 20.4 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Part 4 | 7.28 Hours | Geometric Coefficient of Variation 30.6 |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 and 3 who received MK-1092 and complied with the protocol (treatments, measurements, major protocol deviations) so that data exhibited effects of treatment. For the MK-1092 4.0 and 64 nmol/kg groups, 5 and 1 participants, respectively, were excluded (insufficient terminal phase data).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3 | 6.39 Hours | — |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3 | 6.17 Hours | Geometric Coefficient of Variation 29.3 |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3 | 5.41 Hours | Geometric Coefficient of Variation 28.7 |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3 | 5.84 Hours | Geometric Coefficient of Variation 16.5 |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3 | 9.27 Hours | Geometric Coefficient of Variation 71.1 |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3 | 8.54 Hours | Geometric Coefficient of Variation 23.2 |
| Part 1 (Healthy Adults) Post-trial | Time to Reach a 50% Decrease In Plasma MK-1092 Concentration (t1/2) Parts 1 and 3 | 6.70 Hours | Geometric Coefficient of Variation 31.4 |
Secondary
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.
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) ]
Population: The analysis population included participants in Part 4 who received glargine and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment, per the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach Maximum Plasma Insulin Glargine Concentration (Tmax) Part 4 | 1.00 Hr |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach Maximum Plasma Insulin Glargine Concentration (Tmax) Part 4 | 2.00 Hr |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time to Reach Maximum Plasma Insulin Glargine Concentration (Tmax) Part 4 | 2.98 Hr |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 and 3 who received glargine and complied with the protocol so that data likely exhibited effects of treatment. One participant (Part 1) was excluded (no quantifiable glargine concentration). Data across panels were pooled for Parts 1 and 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach Maximum Plasma Insulin Glargine Concentration (Tmax) Parts 1 and 3 | 1.98 Hours |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach Maximum Plasma Insulin Glargine Concentration (Tmax) Parts 1 and 3 | 1.74 Hours |
Secondary
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.
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)
Population: The analysis population included participants in Part 4 who received MK-1092 and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment, per the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Part 4 | 14.99 Hours |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Part 4 | 18.00 Hours |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Part 4 | 21.04 Hours |
Secondary
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.
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)
Population: The analysis population included participants in Parts 1 and 3 who received MK-1092 and complied with the protocol sufficiently to ensure that data were likely to exhibit the effects of treatment, per the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3 | 18.00 Hours |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3 | 12.00 Hours |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3 | 18.00 Hours |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3 | 18.00 Hours |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3 | 12.00 Hours |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3 | 15.00 Hours |
| Part 1 (Healthy Adults) Post-trial | Time to Reach Maximum Plasma MK-1092 Concentration (Tmax) Parts 1 and 3 | 15.04 Hours |
Secondary
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.
Time frame: Up to approximately 24 hours post-dose
Population: 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, absence of major protocol deviations. The glargine treatment group was pooled (n=2 participants per panel).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T1DM (Part 3) | 0.72 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T1DM (Part 3) | 1.92 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T1DM (Part 3) | 1.18 mg/kg/min |
Secondary
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.
Time frame: Up to approximately 24 hours post-dose
Population: The analysis population included participants in Part 4 who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance included exposure to treatment, availability of measurements, and absence of major protocol deviations.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4) | 1.02 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4) | 0.78 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4) | 1.70 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4) | 0.50 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4) | 0.64 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Adult Participants With T2DM (Part 4) | 0.67 mg/kg/min |
Secondary
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.
Time frame: Up to approximately 24 hours post-dose
Population: The analysis population included participants in Part 1 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1 (Healthy Adults) Glargine 3.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 0.49 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 4.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 0.97 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 8.0 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 2.02 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 16 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 1.97 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 32 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 2.87 mg/kg/min |
| Part 1 (Healthy Adults) MK-1092 64 Nmol/kg | Time-Weighted Average GIR (TWA[GIR]) After a Single Dose Administration of Subcutaneous MK-1092 or Glargine to Healthy Adult Participants (Part 1) | 1.70 mg/kg/min |