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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)

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-0893 10 mg
MK-0893 40 mg
MK-0893 200 mg
MK-0893 1000 mg
Placebo
Sandostatine®
Insulin
Glucagon
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring 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

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

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®.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    MK-0893 40 mg→MK-0893 200 mg→placebo

    MK-0893 200 mg→placebo→MK-0893 10 mg

    Placebo→MK-0893 10 mg→MK-0893 40 mg

    MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg

    Placebo→MK-0893 1000 mg→MK-0893 200 mg

    MK-0893 200 mg→placebo→MK-0893 1000 mg

    MK-0893 1000 mg→MK-0893 200 mg→placebo

    Arm Description

    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.

    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.

    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.

    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.

    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.

    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.

    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.

    Outcomes

    Primary Outcome Measures

    Post-infusion Incremental Glucose Area Under the Plasma Concentration Versus Time Curve [AUC0-240 min] Study Part 1
    Post-infusion Incremental Glucose Area Under the Plasma Concentration Versus Time Curve [AUC0-240 min] Study Part 2

    Secondary Outcome Measures

    Number of Participants With An Adverse Event (AE)
    Number of Participants Who Discontinued Study Treatment Due To AEs

    Full Information

    First Posted
    December 3, 2013
    Last Updated
    August 18, 2015
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02012166
    Brief Title
    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)
    Official Title
    A Double-Blind, Randomized, Placebo-Controlled, Single-Dose, 3-Period, 4 Treatment Incomplete Crossover Study to Assess the Effects of Single Oral Doses of L-001241689 on Glucagon-Induced Glycemic Excursion in Healthy Male Subjects Following Intravenous Administration of Glucagon, Sandostatine® and Insulin
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    July 2005 (undefined)
    Primary Completion Date
    December 2005 (Actual)
    Study Completion Date
    December 2005 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 2 Diabetes Mellitus
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    18 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    MK-0893 40 mg→MK-0893 200 mg→placebo
    Arm Type
    Experimental
    Arm Description
    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.
    Arm Title
    MK-0893 200 mg→placebo→MK-0893 10 mg
    Arm Type
    Experimental
    Arm Description
    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.
    Arm Title
    Placebo→MK-0893 10 mg→MK-0893 40 mg
    Arm Type
    Experimental
    Arm Description
    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.
    Arm Title
    MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg
    Arm Type
    Experimental
    Arm Description
    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.
    Arm Title
    Placebo→MK-0893 1000 mg→MK-0893 200 mg
    Arm Type
    Experimental
    Arm Description
    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.
    Arm Title
    MK-0893 200 mg→placebo→MK-0893 1000 mg
    Arm Type
    Experimental
    Arm Description
    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.
    Arm Title
    MK-0893 1000 mg→MK-0893 200 mg→placebo
    Arm Type
    Experimental
    Arm Description
    In Part 1 of the study, participants receive MK-0893 (10 mg, 40 mg or 200 mg) or placebo on Day 1 of each period, and Sandostatine® (30 ng/kg/min), insulin (0.10 mIU/kg/min), and glucagon (3 ng/kg/min) at 24 and 72 hours post dose. In Part 2 of the study, participants receive MK-0893 (200 mg or 1000 mg) or placebo on Day 1 of each period and Sandostatine®, insulin, and glucagon at 120 hours post dose. There will be at least 21 days between administrations of study drugs.
    Intervention Type
    Drug
    Intervention Name(s)
    MK-0893 10 mg
    Intervention Description
    MK-0893 10 mg administered orally in 240 mL of water
    Intervention Type
    Drug
    Intervention Name(s)
    MK-0893 40 mg
    Intervention Description
    MK-0893 40 mg administered orally in 240 mL of water
    Intervention Type
    Drug
    Intervention Name(s)
    MK-0893 200 mg
    Intervention Description
    MK-0893 200 mg administered orally in 240 mL of water
    Intervention Type
    Drug
    Intervention Name(s)
    MK-0893 1000 mg
    Intervention Description
    MK-0893 1000 mg administered orally in 240 mL of water
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo administered orally in 240 mL of water
    Intervention Type
    Biological
    Intervention Name(s)
    Sandostatine®
    Other Intervention Name(s)
    Octreotide acetate
    Intervention Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    Insulin
    Other Intervention Name(s)
    Humuline Regular, Insulin for human injection
    Intervention Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    Glucagon
    Other Intervention Name(s)
    Glucagen
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    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
    Title
    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 Outcome Measure Information:
    Title
    Number of Participants With An Adverse Event (AE)
    Time Frame
    Up to 12 weeks
    Title
    Number of Participants Who Discontinued Study Treatment Due To AEs
    Time Frame
    Up to 21 days of each treatment period

    10. Eligibility

    Sex
    Male
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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®.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    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)

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