A Study of MK-0893 on Glucagon-Induced Glycemic Excursion in Healthy Male Participants Following Intravenous Administration of Glucagon, Sandostatine® and Insulin (MK-0893-002)

Phase 1CompletedNCT02012166

Merck Sharp & Dohme LLC18 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Type 2 Diabetes Mellitus

Interventions

Sandostatine®BIOLOGICAL

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.

InsulinBIOLOGICAL

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.

GlucagonBIOLOGICAL

Eligibility

Sex: MALEMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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®.

Outcomes

Primary Outcomes

Post-infusion Incremental Glucose Area Under the Plasma Concentration Versus Time Curve [AUC0-240 min] Study Part 1

Time frame: Up to 76 hours postdose

Post-infusion Incremental Glucose Area Under the Plasma Concentration Versus Time Curve [AUC0-240 min] Study Part 2

Time frame: Up to 124 hours postdose

Secondary Outcomes

Number of Participants With An Adverse Event (AE)

Time frame: Up to 12 weeks

Number of Participants Who Discontinued Study Treatment Due To AEs

Time frame: Up to 21 days of each treatment period