single ascending dose study of mk-1092 in healthy participants and in participants with type 1 and type 2 diabetes mellitus (mk-1092-001)

Conditions: Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus

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)

there will be 4 parts in this study. in part 1, healthy adult participants will be randomized to receive blinded mk-1092 subcutaneously (sc) or glargine sc, as a single dose under the euglycemic clamp. once a safe and tolerated dose that achieves girmax is identified in part 1, part 2 will start. in part 2, 4 different healthy adult participants will be enrolled in a single panel and receive open-label mk-1092 sc as a single dose under the euglycemic clamp and also receive an intravenous infusion of humalog®. in part 3, adult participants with t1dm will be randomized to receive blinded mk-1092 sc or insulin glargine sc, as a single dose under the euglycemic clamp. part 4 includes a 3-period (periods 1, 2, and 3) design that will explore up to 3 single subcutaneous doses of mk-1092 or insulin glargine in participants with type 2 diabetes mellitus.

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.