The purpose of this study is to assess the safety, pharmacokinetics, and pharmacodynamics of MK-1293 compared with a basal insulin (EU-Lantus™) in participants with Type 1 Diabetes. The primary hypotheses are that the duration of action, pharmacodynamic profile, and pharmacokinetic profile of MK-1293 and the comparator basal insulin are similar.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
76
MK-1293 0.4 units/kg administered subcutaneously
EU-Lantus™ 0.4 units/kg administered subcutaneously
Participants will receive an intravenous infusion of insulin aspart (Novolog™ or other rapid-acting insulin analog) for several hours prior to MK-1293 or EU-Lantus™ dosing in each dosing period to meet basal insulin requirements
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
Time frame: Up to 30 hours postdose
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
The area under the glucose infusion rate curve from hours 0 to 24 after injection (AUC\[GIR{0-24}\]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time frame: Up to 24 hours postdose
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
The area under the glucose infusion rate curve from hours 0 to 12 after injection (AUC\[GIR{0-12}\]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time frame: Up to 12 hours postdose
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
The area under the glucose infusion rate curve from hours 12 to 24 after injection (AUC\[GIR{12-24}\]) for participants who received either MK-1293 or Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time frame: From 12 to 24 hours postdose
PD: Maximum Glucose Infusion Rate (GIRmax)
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Maximum glucose infusion rate (GIR\[max\]) based on smoothed data for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Time frame: Up to 30 hours postdose
M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Analysis was performed on log scale with results back transformed to the original scale
Time frame: Up to 24 hours postdose
M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Analysis was performed on log scale with results back transformed to original scale.
Time frame: Up to 24 hours postdose
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-12 is a measure of the total amount of drug in the plasma from the dose to Hour 12. Analysis was performed on log scale with results back transformed to original scale.
Time frame: Up to 12 hours postdose
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC12-24 is a measure of the total amount of drug in the plasma from Hour 12 to Hour 24. Analysis was performed on log scale with results back transformed to original scale.
Time frame: From 12 to 24 hours postdose