Single Ascending Dose Study of MK-1092 in Healthy Participants and in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-1092-001)
Condition: Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
Intervention: MK-1092, 4.0 nmol/kg; MK-1092, 8.0 nmol/kg; MK-1092, 16 nmol/kg; MK-1092, 32 nmol/kg; MK-1092, 64 nmol/kg; Glargine 3.0 nmol/kg; Lispro 1.2 nmol/kg; Placebo to glargine; Placebo to MK-1092; Dextrose; Insulin
Intervention description: MK-1092, 4.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants; MK-1092, 8.0 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants; MK-1092, 16 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants; MK-1092, 32 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants; MK-1092, 64 nmol/kg, SC, as a single dose under the euglycemic clamp, in participants; Glargine 3.0 nmol/kg, SC, as a single dose; 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; Placebo to MK-1092, SC, as a single dose; 20% solution for continuous infusion for the duration of the glucose clamp as needed to maintain blood sugar at pre-clamp target levels.; Participants will receive insulin IV, as needed, prior to dosing and clamp initiation and after dosing.
Intervention MeSH terms: Insulin Glargine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

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)
    

Eligibility 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.