Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Therapeutic Uses, Pharmacologic Actions, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs
Brief summary
This is a study to assess the pharmacokinetics, safety, and tolerability of sequential single oral doses of MK-8093 10 mg, 40 mg, 200 mg, or placebo to MK-8093 (Part 1) depending on treatment assignment in young healthy male participants. In Part 2 of this study, sequential single oral doses of MK-8093 200 mg, 1000 mg or placebo to MK-8093 depending on treatment assignment will be evaluated. The primary hypothesis of the study is that at least one dose of MK-0893 will produce greater reduction of glucagon-induced glycemia as compared to placebo following the infusion of glucagon, Sandostatine®, and basal insulin.
Interventions
DRUGMK-0893 10 mg
MK-0893 10 mg administered orally in 240 mL of water
DRUGMK-0893 40 mg
MK-0893 40 mg administered orally in 240 mL of water
DRUGMK-0893 200 mg
MK-0893 200 mg administered orally in 240 mL of water
DRUGMK-0893 1000 mg
MK-0893 1000 mg administered orally in 240 mL of water
DRUGPlacebo
Placebo administered orally in 240 mL of water
BIOLOGICALSandostatine®
Sandostatine® is a somatostatin analogue. At 24 and at 72 (Part I) or 120 (Part II) hours postdose, simultaneous infusions of the Sandostatine®, insulin, and glucagon will be administered over a 2-hour period. These compounds are IV compatible and will be combined in one syringe. Intravenous Sandostatine® will be administered at 30 ng/kg/min.
BIOLOGICALInsulin
At 24 and at 72 (Part I) or 120 (Part II) hours postdose, simultaneous infusions of the Sandostatine®, insulin, and glucagon will be administered over a 2-hour period. These compounds are IV compatible and will be combined in one syringe. Intravenous insulin will be administered at 0.10 milli-international unit (mIU)/kg/min.
BIOLOGICALGlucagon
At 24 and at 72 (Part I) or 120 (Part II) hours postdose, simultaneous infusions of the Sandostatine®, insulin, and glucagon will be administered over a 2-hour period. These compounds are IV compatible and will be combined in one syringe. Intravenous glucagon will be administered at 3 ng/kg/min.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Good health * Body Mass Index of between 18 and 28 kg/m\^2, or up to 30 kg/m\^2 with approval of sponsor * Non-smoker for at least 6 months * Willing to avoid strenuous physical activity * Willing to avoid alcohol, caffeine, and grapefruit juice consumption
Exclusion criteria
* History of renal, neurologic, gastrointestinal or respiratory disease or any gastrointestinal surgery * History of multiple and/or severe allergies to a prescription, nonprescription or investigational drug or food * History of any cardiovascular/cardiac disease * History of any hepatic disease and primary biliary cirrhosis * History of hypoglycemia or glucose intolerance, type 1 diabetes, or type 2 diabetes * Requires or anticipates use of prescription or nonprescription medications, including herbal remedies * A user of any illicit drugs or a history of drug or alcohol abuse * Surgery, donated a unit of blood, or participated in another clinical study within 4 weeks prior to study participation * History of hypersensitivity to insulin, glucagon, or Sandostatine®.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Post-infusion Incremental Glucose Area Under the Plasma Concentration Versus Time Curve [AUC0-240 min] Study Part 1 | Up to 76 hours postdose |
| Post-infusion Incremental Glucose Area Under the Plasma Concentration Versus Time Curve [AUC0-240 min] Study Part 2 | Up to 124 hours postdose |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With An Adverse Event (AE) | Up to 12 weeks |
| Number of Participants Who Discontinued Study Treatment Due To AEs | Up to 21 days of each treatment period |
Outcome results
None listed