Multiple Ascending Dose Study of MK-5160 in Participants... | NCT03095651

NCT03095651

ID	Type	Description	Link
MK-5160-002	Other Identifier	Merck protocol number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
T1DM MK-5160 16 nmol/kg	Experimental	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.	Biological: MK-5160 16 nmol/kg Biological: Placebo to Glargine Drug: Dextrose
T1DM MK-5160 32 nmol/kg	Experimental	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.	Biological: MK-5160 32 nmol/kg Biological: Placebo to Glargine Drug: Dextrose
T1DM MK-5160 64 nmol/kg	Experimental	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.	Biological: MK-5160 64 nmol/kg Biological: Placebo to Glargine Drug: Dextrose
T1DM Glargine 0.4 U/kg	Active Comparator	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.	Biological: Glargine 0.4 U/kg Biological: Placebo to MK-5160 Drug: Dextrose
T2DM MK-5160 16 nmol/kg

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MK-5160 16 nmol/kg	Biological	MK-5160 16 nmol/kg, subcutaneous injection administered daily for 12 days	T1DM MK-5160 16 nmol/kg T2DM MK-5160 16 nmol/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Up to 33 days
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.	Up to 12 days
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.	Up to 24 hours post-dose on Day 12

Secondary Outcomes

Measure	Description	Time Frame
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.	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.

Eligibility Module

Eligibility Criteria

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.

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
ProSciento Inc. ( Site 0001)		Chula Vista	California	91911	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	T1DM MK-5160 32 Nmol/kg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 27, 2017

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

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.

No participants were randomized to the T1DM MK-5160 64 nmol/kg arm or the T2DM MK-5160 16 nmol/kg arm.

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	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.
BG005	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.
BG006	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.
BG007	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.
BG008	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG0020 BG0034 BG0040 BG0057 BG0066 BG0074 BG00833

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Between 18 and 64 years	BG0006 BG0016 BG0020 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Black or African American	BG0000 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Count of Participants

Participants

Up to 33 days

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.
OG004	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.
OG005	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.
OG006	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.
OG007	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.

Units	Counts
Participants	OG0006 OG0016 OG0020 OG003

Title

Denominators

Categories

Title	Measurements
	OG0006 OG0016 OG0020 OG003

Primary

Number of Participants Discontinuing Study Drug Due to an AE

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.

Posted

Count of Participants

Participants

Up to 12 days

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

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.

Posted

Mean

95% Confidence Interval

mg/kg/min

Up to 24 hours post-dose on Day 12

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

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.

Posted

Geometric Mean

95% Confidence Interval

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	T1DM MK-5160 64 Nmol/kg

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.

All participants that received glargine, had no major protocol violations, and had Cmax values available on Day 1 and Day 12.

Posted

Geometric Mean

95% Confidence Interval

pmol/L

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

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.

Posted

Geometric Mean

90% Confidence Interval

Ratio

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

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.

Posted

Geometric Mean

95% Confidence Interval

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

All participants that received glargine, had no major protocol violations, and had Css values available on Day 12.

Posted

Geometric Mean

95% Confidence Interval

pmol/L

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

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.

Posted

Geometric Mean

95% Confidence Interval

hr*nM

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	T1DM MK-5160 64 Nmol/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.

All participants that received glargine, had no major protocol violations, and had AUC0-24 values available on Day 1 and Day 12.

Posted

Geometric Mean

95% Confidence Interval

hr*pmol/L

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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

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.

Posted

Geometric Mean

90% Confidence Interval

Ratio

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Plasma Clearance

Plasma Clearance (CL) of study drug is the volume of plasma cleared of study drug per unit time.

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.

Posted

Geometric Mean

95% Confidence Interval

L/hr/kg

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.

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003

Secondary

Time to Maximum Plasma Concentration

Time to reach the maximum plasma concentration (Tmax) of study drug after the dose is given.

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.

Posted

Median

Full Range

hour

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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%.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

hour

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	6	6	6
EG001	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	6	6	6
EG002	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	0	0	0
EG003	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	4	4	4
EG004	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	0	0	0
EG005	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	7	7	7
EG006	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	6	6	6
EG007	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	4	4	4

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected6 at risk EG0020 events0 affected0 at risk EG0030 events0 affected4 at risk EG0040 events0 affected0 at risk EG0050 events0 affected7 at risk EG0060 events0 affected6 at risk EG0071 events1 affected4 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Infusion site extravasation	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Injection site erythema	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Injection site haemorrhage	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Injection site pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Injection site nodule	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Thirst	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Feeling cold	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Hordeolum	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Blood glucose increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG00068 events6 affected6 at risk EG00154 events5 affected6 at risk EG0020 events0 affected0 at risk EG003
Pseuodohypoglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0006 events2 affected6 at risk EG00113 events5 affected6 at risk EG0020 events0 affected0 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Lethargy	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected0 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0014 events4 affected6 at risk EG0020 events0 affected0 at risk EG003
Vision blurred	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0004 events3 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected0 at risk EG003

ID	Term
D003922	Diabetes Mellitus, Type 1
D003924	Diabetes Mellitus, Type 2

Ancestor Terms

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D000069036	Insulin Glargine
D005947	Glucose

Ancestor Terms

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D006601	Hexoses
D009005	Monosaccharides
D000073893	Sugars
D002241	Carbohydrates

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.