Multiple Ascending Dose Study of MK-5160 in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-5160-002)
Condition: Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
Intervention: MK-5160 16 nmol/kg; MK-5160 32 nmol/kg; MK-5160 64 nmol/kg; Glargine 0.4 U/kg; Placebo to Glargine; Placebo to MK-5160; Dextrose; Glargine 0.6 U/kg
Intervention description: MK-5160 16 nmol/kg, subcutaneous injection administered daily for 12 days; MK-5160 32 nmol/kg, subcutaneous injection administered daily for 12 days; MK-5160 64 nmol/kg, subcutaneous injection administered daily for 12 days; Glargine 0.4 U/kg, subcutaneous injection administered daily for 12 days; Placebo to glargine, subcutaneous injection administered daily for 12 days; Placebo to MK-5160, subcutaneous injection administered daily for 12 days; 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.; Glargine 0.6 U/kg, subcutaneous injection administered daily for 12 days
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: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

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.