Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a randomized, active- and placebo-controlled, double-blind trial of MK-5160 in participants with Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). This is a two-part trial, with three panels per part. T1DM (Part 1) and T2DM (Part 2) participants will be given daily fixed doses of MK-5160 in three predefined, increasing doses in each panel, or glargine (active comparator). The primary hypothesis of the trial is that at a dose with sufficient safety, the mean steady-state maximum level of glucose infusion rate (GIRmax) after MK-5160 administration in both T1DM and T2DM participants is between 1.5 and 4.5 mg/kg/min.
Interventions
BIOLOGICALMK-5160 16 nmol/kg
MK-5160 16 nmol/kg, subcutaneous injection administered daily for 12 days
BIOLOGICALMK-5160 32 nmol/kg
MK-5160 32 nmol/kg, subcutaneous injection administered daily for 12 days
BIOLOGICALMK-5160 64 nmol/kg
MK-5160 64 nmol/kg, subcutaneous injection administered daily for 12 days
BIOLOGICALGlargine 0.4 U/kg
Glargine 0.4 U/kg, subcutaneous injection administered daily for 12 days
BIOLOGICALPlacebo to Glargine
Placebo to glargine, subcutaneous injection administered daily for 12 days
BIOLOGICALPlacebo to MK-5160
Placebo to MK-5160, subcutaneous injection administered daily for 12 days
DRUGDextrose
20% solution of dextrose; adjusted to maintain the various glycemic levels at 100 mg/dL given as a continuous intravenous infusion for 6-30 hours.
BIOLOGICALGlargine 0.6 U/kg
Glargine 0.6 U/kg, subcutaneous injection administered daily for 12 days
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 65 Years
Healthy volunteers
No
Inclusion criteria
* For Part 1 (T1DM): * Be male, or female of non-childbearing potential. A female of non-childbearing potential defined as a female who is postmenopausal without menses for at least 1 year and has a follicle stimulating hormone (FSH) value in the postmenopausal range upon pretrial (screening) evaluation OR a female who is status post hysterectomy, oophorectomy or tubal ligation. * Be judged to be in good health * Have a diagnosis of T1DM as defined by standard diagnostic criteria for ≥12 months at time study participation * 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. * Have a hemoglobin A1C (HbA1c) ≤10% at the time of study participation. * Have a Body Mass Index (BMI) ≥18.5 kg/m\^2 and ≤ 32 kg/m\^2. BMI = mass (kg)/height (m)\^2 * 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). The subject must agree to follow the smoking restrictions defined by the clinical research unit (CRU). * For Part 2 (T2DM): * Be male, or female of non-childbearing potential. A female of non-childbearing potential defined as a female who is postmenopausal without menses for at least 1 year and has a FSH value in the postmenopausal range upon pretrial (screening) evaluation OR a female who is status post hysterectomy, oophorectomy or tubal ligation. * Be judged to be in good health * Have a diagnosis of T2DM as defined by standard diagnostic criteria for ≥12 month at time of study participation. * T2DM participants are not required to have been on insulin. If on insulin, participants 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. * Meet one of the following criteria: 1. Be on no anti-hyperglycemic agent (AHA), or on metformin monotherapy or metformin plus a dipeptidyl peptidase-4 (DPP4) inhibitor at stable doses for at least 8 weeks prior to screening, with a screening HbA1C ≥7.0 and ≤10.0%. 2. Be on either a sulfonylurea (e.g. glyburide) or an alpha-glucosidase inhibitors (e.g., acarbose) alone or in combination with metformin at stable doses for at least 8 weeks prior to screening with a screening HbA1C ≥7.0 and ≤9.0%. Participants on these medications must be willing to stop the sulfonylurea or alpha-glucosidase inhibitor after screening once they qualify for study participation. * Have a BMI ≥18.5 kg/m\^2 and ≤ 35.0 kg/m\^2 BMI = mass (kg)/height (m)\^2 * May be on selected standard medications for T2DM, including alpha-glucosidase inhibitors (e.g., acarbose), sulfonylureas (e.g. glyburide), DPP-4 inhibitors, and metformin. Participants on alpha-glucosidase inhibitors and/or sulfonylureas must stop these medications for at least one week prior to checking into the site and for the duration of the trial through the last dose of MK-5160/glargine. Participants on metformin or DPP-4 inhibitors may continue on their home dose for the duration of the trial. Participants on SGLT2 inhibitors (gliflozins), thiazolidinediones or GLP-1 agonists are excluded. * Be a nonsmoker or smoker who uses no greater than 5 cigarettes or equivalent (e.g., e-cigarettes) daily over the prior 3 month period. Participants must agree to follow the smoking restrictions defined by the CRU.
Exclusion criteria
* For Part 1 (T1DM) and Part 2 (T2DM): * Is under the age of legal consent * Is mentally or legally incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the trial at the discretion of the investigator. * Has a history of clinically significant endocrine (excluding diabetes mellitus), gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a history of uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the last 5 years, or childhood asthma may be enrolled in the trial at the discretion of the investigator. * 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 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. * Is positive for hepatitis B surface antigen, hepatitis C antibodies or HIV at Screening. * Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial visit. * Has participated in another investigational trial within 4 weeks (or 5 half-lives), whichever is greater, prior to the pretrial visit. * 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 (or 5 half-lives) prior to administration of the initial dose of trial drug, throughout the trial (including washout intervals between treatment periods), until the post-trial visit. Certain medications, such as antihypertensives and aspirin, are permitted. * Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day. * Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day. * Is a regular user of cannabis or any illicit drugs, or has a history of drug (including alcohol) abuse within approximately 6 months. * 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 used systemic (intravenous, oral, inhaled) glucocorticoids within 3 months of screening or is anticipated to require treatment with systemic glucocorticoids during study participation. * Has other major medical problems requiring medication (i.e., history of myocardial infarction, hypercholesterolemia). Participants on aspirin as prophylaxis may be enrolled, provided there is no history of MI or other thromboembolic event, or a history of coronary atherosclerosis. * 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 regular human insulin, or to any E.coli-derived drug product. * For Part 1 (T1DM) Only: * Has a history of diabetic ketoacidosis in the last 12 months. * For Part 2 (T2DM) Only * Has been treated with a sodium/glucose cotransporter 2 (SGLT2) inhibitor (gliflozins), thiazolidinedione or Glucagon-like peptide-1 (GLP-1) receptor agonist within the past three months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing an Adverse Event (AE) | Up to 33 days | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Discontinuing Study Drug Due to an AE | Up to 12 days | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Maximal Glucose Infusion Rate | Up to 24 hours post-dose on Day 12 | Maximal glucose infusion rate required to maintain target glucose levels in a euglycemic clamp setting (GIRmax) at steady state (Day 12) following administration of study drug. In cases where the lower bound of the CI was negative, the lower confidence limit was truncated at zero. In these cases, the confidence intervals are 97.5% CIs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steady State Plasma Concentration (Css) of MK-5160 | Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Css of MK-5160 is the amount of MK-5160 in a given volume of plasma at the time a steady state has been achieved, and rates of MK-5160 administration and MK-5160 elimination are equal. Glargine data are presented in the following outcome measure. |
| Steady State Plasma Concentration (Css) of Glargine | Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Css of glargine is the amount of glargine in a given volume of plasma at the time a steady state has been achieved, and rates of glargine administration and glargine elimination are equal. MK-5160 data are presented in the preceding outcome measure. |
| Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. | Area Under the Plasma Concentration/Time Curve for MK-5160 from Time 0 to 24 hours (AUC0-24) is a measure of the total amount of MK-5160 in the plasma from the dose administration to 24 hours. Glargine data are presented in the following outcome measure. |
| Plasma Concentration/Time (AUC0-24) of Glargine | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. | AUC0-24 is a measure of the total amount of glargine in the plasma from the dose administration to 24 hours. MK-5160 data are presented in the preceding outcome measure. |
| Maximum Plasma Concentration (Cmax) of MK-5160 | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours following start of injection (FSOI). Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Cmax of MK-5160 following multiple dose administration of study drug. Glargine data are presented in the following outcome measure. |
| Plasma Clearance | Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Plasma Clearance (CL) of study drug is the volume of plasma cleared of study drug per unit time. |
| Time to Maximum Plasma Concentration | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Time to reach the maximum plasma concentration (Tmax) of study drug after the dose is given. |
| Apparent Terminal Half-life | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Apparent Terminal Half-life (t1/2) is the time required for a given MK-5160 concentration in the plasma to decrease by 50%. |
| Day 12 to Day 1 Accumulation Ratio of AUC0-24. | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. | Day 12 to Day 1 Accumulation Ratio (AR) of the AUC0-24 of study drug (MK-5160 or glargine). Geometric mean accumulation ratio = Day 12 AUC0-24/Day 1 AUC0-24 |
| Maximum Plasma Concentration (Cmax) of Glargine | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Cmax of glargine following multiple dose administration of study drug. MK-5160 data are presented in the preceding outcome measure. |
| Day 12 to Day 1 Accumulation Ratio of Cmax | Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI. | Day 12 to Day 1 accumulation ratio (AR) of Cmax of MK-5160 and glargine following multiple dose administration of study drug. Geometric mean accumulation ratio = Day 12 Cmax/Day 1 Cmax. |
Countries
United States
Participant flow
Pre-assignment details
No participants were randomized to the T1DM (Type 1 Diabetes Mellitus) MK-5160 64 nmol/kg arm or the T2DM (Type 2 Diabetes Mellitus) MK-5160 16 nmol/kg arm.
Participants by arm
| Arm | Count |
|---|---|
| T1DM MK-5160 16 Nmol/kg Participants with T1DM received MK-5160, 16 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 6 |
| T1DM MK-5160 32 Nmol/kg Participants with T1DM received MK-5160, 32 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 6 |
| T1DM MK-5160 64 Nmol/kg Participants with T1DM received MK-5160 64 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 0 |
| T1DM Glargine 0.4 U/kg Participants with T1DM received Glargine 0.4 U/kg and placebo to MK-5160 daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 4 |
| T2DM MK-5160 16 Nmol/kg Participants with T2DM received MK-5160 16 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 0 |
| T2DM MK-5160 32 Nmol/kg Participants with T2DM received MK-5160 32 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 7 |
| T2DM MK-5160 64 Nmol/kg Participants with T2DM received MK-5160 64 nmol/kg, and placebo to glargine daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 6 |
| T2DM Glargine 0.6 U/kg Participants with T2DM received Glargine 0.6 U/kg and placebo to MK-5160 daily for 12 days. Dextrose was administered as needed to maintain blood sugar. | 4 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | T1DM MK-5160 16 Nmol/kg | T1DM MK-5160 32 Nmol/kg | T1DM MK-5160 64 Nmol/kg | T1DM Glargine 0.4 U/kg | T2DM MK-5160 16 Nmol/kg | T2DM MK-5160 32 Nmol/kg | T2DM MK-5160 64 Nmol/kg | T2DM Glargine 0.6 U/kg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized Between 18 and 64 years | 6 Participants | 6 Participants | 0 Participants | 4 Participants | 0 Participants | 6 Participants | 6 Participants | 4 Participants | 32 Participants |
| Age, Customized From 65 to 84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 5 Participants | 0 Participants | 4 Participants | 0 Participants | 7 Participants | 6 Participants | 4 Participants | 32 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 0 Participants | 4 Participants | 0 Participants | 3 Participants | 6 Participants | 3 Participants | 27 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 4 | 0 / 0 | 0 / 7 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 0 / 0 | 4 / 4 | 0 / 0 | 7 / 7 | 6 / 6 | 4 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 0 | 0 / 4 | 0 / 0 | 0 / 7 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Maximal Glucose Infusion Rate
Maximal glucose infusion rate required to maintain target glucose levels in a euglycemic clamp setting (GIRmax) at steady state (Day 12) following administration of study drug. In cases where the lower bound of the CI was negative, the lower confidence limit was truncated at zero. In these cases, the confidence intervals are 97.5% CIs.
Time frame: Up to 24 hours post-dose on Day 12
Population: All participants that received study drug, had no major protocol violations, and had GIRmax values available on Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Maximal Glucose Infusion Rate | 2.15 mg/kg/min |
| T1DM MK-5160 32 Nmol/kg | Maximal Glucose Infusion Rate | 2.86 mg/kg/min |
| T1DM Glargine 0.4 U/kg | Maximal Glucose Infusion Rate | 2.56 mg/kg/min |
| T2DM MK-5160 32 Nmol/kg | Maximal Glucose Infusion Rate | 1.98 mg/kg/min |
| T2DM MK-5160 64 Nmol/kg | Maximal Glucose Infusion Rate | 2.15 mg/kg/min |
| T2DM Glargine 0.6 U/kg | Maximal Glucose Infusion Rate | 3.25 mg/kg/min |
Primary
Number of Participants Discontinuing Study Drug Due to an AE
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 12 days
Population: All participants who received at least one dose of study drug. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| T1DM MK-5160 32 Nmol/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| T1DM MK-5160 64 Nmol/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| T1DM Glargine 0.4 U/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| T2DM MK-5160 16 Nmol/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| T2DM MK-5160 32 Nmol/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| T2DM MK-5160 64 Nmol/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
| T2DM Glargine 0.6 U/kg | Number of Participants Discontinuing Study Drug Due to an AE | 0 Participants |
Primary
Number of Participants Experiencing an Adverse Event (AE)
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 33 days
Population: All participants who received at least one dose of study drug. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Number of Participants Experiencing an Adverse Event (AE) | 6 Participants |
| T1DM MK-5160 32 Nmol/kg | Number of Participants Experiencing an Adverse Event (AE) | 6 Participants |
| T1DM MK-5160 64 Nmol/kg | Number of Participants Experiencing an Adverse Event (AE) | 0 Participants |
| T1DM Glargine 0.4 U/kg | Number of Participants Experiencing an Adverse Event (AE) | 4 Participants |
| T2DM MK-5160 16 Nmol/kg | Number of Participants Experiencing an Adverse Event (AE) | 0 Participants |
| T2DM MK-5160 32 Nmol/kg | Number of Participants Experiencing an Adverse Event (AE) | 7 Participants |
| T2DM MK-5160 64 Nmol/kg | Number of Participants Experiencing an Adverse Event (AE) | 6 Participants |
| T2DM Glargine 0.6 U/kg | Number of Participants Experiencing an Adverse Event (AE) | 4 Participants |
Secondary
Apparent Terminal Half-life
Apparent Terminal Half-life (t1/2) is the time required for a given MK-5160 concentration in the plasma to decrease by 50%.
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: All participants that received MK-5160, had no major protocol violations, and had t1/2 values available on Day 1 and Day 12. t1/2 was not calculated for the Glargine 0.4 U/kg and 0.6 U/kg arms. No participants were randomized to the T1DM MK-5160 64 nmol/kg or T2DM MK-5160 16 nmol/kg arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Apparent Terminal Half-life | 20.01 hour | Geometric Coefficient of Variation 59.84 |
| T1DM MK-5160 32 Nmol/kg | Apparent Terminal Half-life | 21.69 hour | Geometric Coefficient of Variation 27.7 |
| T2DM MK-5160 32 Nmol/kg | Apparent Terminal Half-life | 13.10 hour | Geometric Coefficient of Variation 36.05 |
| T2DM MK-5160 64 Nmol/kg | Apparent Terminal Half-life | 14.47 hour | Geometric Coefficient of Variation 16.78 |
Secondary
Day 12 to Day 1 Accumulation Ratio of AUC0-24.
Day 12 to Day 1 Accumulation Ratio (AR) of the AUC0-24 of study drug (MK-5160 or glargine). Geometric mean accumulation ratio = Day 12 AUC0-24/Day 1 AUC0-24
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI.
Population: Participants with AUC0-24 measurements on Day 1 and Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of AUC0-24. | 4.38 Ratio |
| T1DM MK-5160 32 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of AUC0-24. | 4.00 Ratio |
| T1DM Glargine 0.4 U/kg | Day 12 to Day 1 Accumulation Ratio of AUC0-24. | 1.24 Ratio |
| T2DM MK-5160 32 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of AUC0-24. | 3.63 Ratio |
| T2DM MK-5160 64 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of AUC0-24. | 5.83 Ratio |
| T2DM Glargine 0.6 U/kg | Day 12 to Day 1 Accumulation Ratio of AUC0-24. | 2.36 Ratio |
Secondary
Day 12 to Day 1 Accumulation Ratio of Cmax
Day 12 to Day 1 accumulation ratio (AR) of Cmax of MK-5160 and glargine following multiple dose administration of study drug. Geometric mean accumulation ratio = Day 12 Cmax/Day 1 Cmax.
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: Participants with Cmax measurements on Day 1 and Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of Cmax | 3.08 Ratio |
| T1DM MK-5160 32 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of Cmax | 3.40 Ratio |
| T1DM Glargine 0.4 U/kg | Day 12 to Day 1 Accumulation Ratio of Cmax | 1.17 Ratio |
| T2DM MK-5160 32 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of Cmax | 2.89 Ratio |
| T2DM MK-5160 64 Nmol/kg | Day 12 to Day 1 Accumulation Ratio of Cmax | 4.72 Ratio |
| T2DM Glargine 0.6 U/kg | Day 12 to Day 1 Accumulation Ratio of Cmax | 1.80 Ratio |
Secondary
Maximum Plasma Concentration (Cmax) of Glargine
Cmax of glargine following multiple dose administration of study drug. MK-5160 data are presented in the preceding outcome measure.
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: All participants that received glargine, had no major protocol violations, and had Cmax values available on Day 1 and Day 12.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| T1DM Glargine 0.4 U/kg | Maximum Plasma Concentration (Cmax) of Glargine | Day 1 | 17.26 pmol/L |
| T1DM Glargine 0.4 U/kg | Maximum Plasma Concentration (Cmax) of Glargine | Day 12 | 20.28 pmol/L |
| T2DM Glargine 0.6 U/kg | Maximum Plasma Concentration (Cmax) of Glargine | Day 1 | 18.97 pmol/L |
| T2DM Glargine 0.6 U/kg | Maximum Plasma Concentration (Cmax) of Glargine | Day 12 | 34.18 pmol/L |
Secondary
Maximum Plasma Concentration (Cmax) of MK-5160
Cmax of MK-5160 following multiple dose administration of study drug. Glargine data are presented in the following outcome measure.
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours following start of injection (FSOI). Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: All participants that received MK-5160, had no major protocol violations, and had Cmax values available on Day 1 and Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg or T2DM MK-5160 16 nmol/kg arms. One participant in the T2DM MK-5160 32 nmol/kg arm withdrew consent after receiving a single dose of study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 1 | 0.76 nM |
| T1DM MK-5160 16 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 12 | 2.33 nM |
| T1DM MK-5160 32 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 12 | 5.38 nM |
| T1DM MK-5160 32 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 1 | 1.58 nM |
| T2DM MK-5160 32 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 12 | 3.85 nM |
| T2DM MK-5160 32 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 1 | 1.33 nM |
| T2DM MK-5160 64 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 1 | 1.91 nM |
| T2DM MK-5160 64 Nmol/kg | Maximum Plasma Concentration (Cmax) of MK-5160 | Day 12 | 9.03 nM |
Secondary
Plasma Clearance
Plasma Clearance (CL) of study drug is the volume of plasma cleared of study drug per unit time.
Time frame: Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: All participants that received study drug, had no major protocol violations, and had CL values available on Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Plasma Clearance | 0.37 L/hr/kg |
| T1DM MK-5160 32 Nmol/kg | Plasma Clearance | 0.30 L/hr/kg |
| T1DM Glargine 0.4 U/kg | Plasma Clearance | 10.01 L/hr/kg |
| T2DM MK-5160 32 Nmol/kg | Plasma Clearance | 0.51 L/hr/kg |
| T2DM MK-5160 64 Nmol/kg | Plasma Clearance | 0.43 L/hr/kg |
| T2DM Glargine 0.6 U/kg | Plasma Clearance | 10.19 L/hr/kg |
Secondary
Plasma Concentration/Time (AUC0-24) of Glargine
AUC0-24 is a measure of the total amount of glargine in the plasma from the dose administration to 24 hours. MK-5160 data are presented in the preceding outcome measure.
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI.
Population: All participants that received glargine, had no major protocol violations, and had AUC0-24 values available on Day 1 and Day 12.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| T1DM Glargine 0.4 U/kg | Plasma Concentration/Time (AUC0-24) of Glargine | Day 1 | 193.6 hr*pmol/L |
| T1DM Glargine 0.4 U/kg | Plasma Concentration/Time (AUC0-24) of Glargine | Day 12 | 239.8 hr*pmol/L |
| T2DM Glargine 0.6 U/kg | Plasma Concentration/Time (AUC0-24) of Glargine | Day 1 | 149.6 hr*pmol/L |
| T2DM Glargine 0.6 U/kg | Plasma Concentration/Time (AUC0-24) of Glargine | Day 12 | 353.3 hr*pmol/L |
Secondary
Plasma Concentration/Time (AUC0-24) of MK-5160
Area Under the Plasma Concentration/Time Curve for MK-5160 from Time 0 to 24 hours (AUC0-24) is a measure of the total amount of MK-5160 in the plasma from the dose administration to 24 hours. Glargine data are presented in the following outcome measure.
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI.
Population: All participants that received MK-5160, had no major protocol violations, and had AUC0-24 values available on Day 1 and Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg or T2DM MK-5160 16 nmol/kg arms. One participant in the T2DM MK-5160 32 nmol/kg arm withdrew consent after receiving a single dose of study drug.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 12 | 42.90 hr*nM |
| T1DM MK-5160 16 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 1 | 9.79 hr*nM |
| T1DM MK-5160 32 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 1 | 26.39 hr*nM |
| T1DM MK-5160 32 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 12 | 105.5 hr*nM |
| T2DM MK-5160 32 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 12 | 63.29 hr*nM |
| T2DM MK-5160 32 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 1 | 17.44 hr*nM |
| T2DM MK-5160 64 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 12 | 147.7 hr*nM |
| T2DM MK-5160 64 Nmol/kg | Plasma Concentration/Time (AUC0-24) of MK-5160 | Day 1 | 25.32 hr*nM |
Secondary
Steady State Plasma Concentration (Css) of Glargine
Css of glargine is the amount of glargine in a given volume of plasma at the time a steady state has been achieved, and rates of glargine administration and glargine elimination are equal. MK-5160 data are presented in the preceding outcome measure.
Time frame: Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: All participants that received glargine, had no major protocol violations, and had Css values available on Day 12.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| T1DM Glargine 0.4 U/kg | Steady State Plasma Concentration (Css) of Glargine | 9.99 pmol/L |
| T2DM Glargine 0.6 U/kg | Steady State Plasma Concentration (Css) of Glargine | 14.72 pmol/L |
Secondary
Steady State Plasma Concentration (Css) of MK-5160
Css of MK-5160 is the amount of MK-5160 in a given volume of plasma at the time a steady state has been achieved, and rates of MK-5160 administration and MK-5160 elimination are equal. Glargine data are presented in the following outcome measure.
Time frame: Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: All participants that received MK-5160, had no major protocol violations, and had Css values available on Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Steady State Plasma Concentration (Css) of MK-5160 | 1.79 nM |
| T1DM MK-5160 32 Nmol/kg | Steady State Plasma Concentration (Css) of MK-5160 | 4.40 nM |
| T2DM MK-5160 32 Nmol/kg | Steady State Plasma Concentration (Css) of MK-5160 | 2.64 nM |
| T2DM MK-5160 64 Nmol/kg | Steady State Plasma Concentration (Css) of MK-5160 | 6.15 nM |
Secondary
Time to Maximum Plasma Concentration
Time to reach the maximum plasma concentration (Tmax) of study drug after the dose is given.
Time frame: Day 1 clamp: -15 min. (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours FSOI. Day 12: -15 min (predose), 10, 30 min., 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 168 hours FSOI.
Population: All participants that received study drug, had no major protocol violations, and had Tmax values available on Day 1 and Day 12. No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T1DM MK-5160 16 Nmol/kg | Time to Maximum Plasma Concentration | Day 1 | 0.75 hour |
| T1DM MK-5160 16 Nmol/kg | Time to Maximum Plasma Concentration | Day 12 | 0.75 hour |
| T1DM MK-5160 32 Nmol/kg | Time to Maximum Plasma Concentration | Day 1 | 0.75 hour |
| T1DM MK-5160 32 Nmol/kg | Time to Maximum Plasma Concentration | Day 12 | 1.00 hour |
| T1DM Glargine 0.4 U/kg | Time to Maximum Plasma Concentration | Day 12 | 1.50 hour |
| T1DM Glargine 0.4 U/kg | Time to Maximum Plasma Concentration | Day 1 | 3.49 hour |
| T2DM MK-5160 32 Nmol/kg | Time to Maximum Plasma Concentration | Day 1 | 1.00 hour |
| T2DM MK-5160 32 Nmol/kg | Time to Maximum Plasma Concentration | Day 12 | 1.00 hour |
| T2DM MK-5160 64 Nmol/kg | Time to Maximum Plasma Concentration | Day 1 | 1.00 hour |
| T2DM MK-5160 64 Nmol/kg | Time to Maximum Plasma Concentration | Day 12 | 1.00 hour |
| T2DM Glargine 0.6 U/kg | Time to Maximum Plasma Concentration | Day 12 | 0.98 hour |
| T2DM Glargine 0.6 U/kg | Time to Maximum Plasma Concentration | Day 1 | 1.49 hour |