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)

NCT02012166 | Completed Phase 1

• 2 other identifiers: 0893-0022005-002198-57
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (7)

MK-0893 40 mg→MK-0893 200 mg→placebo

EXPERIMENTAL

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.

Drug: MK-0893 40 mg; Drug: MK-0893 200 mg; Drug: Placebo; Biological: Sandostatine®; Biological: Insulin; Biological: Glucagon

MK-0893 200 mg→placebo→MK-0893 10 mg

EXPERIMENTAL

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.

Drug: MK-0893 10 mg; Drug: MK-0893 200 mg; Drug: Placebo; Biological: Sandostatine®; Biological: Insulin; Biological: Glucagon

Placebo→MK-0893 10 mg→MK-0893 40 mg

EXPERIMENTAL

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.

Drug: MK-0893 10 mg; Drug: MK-0893 40 mg; Drug: Placebo; Biological: Sandostatine®; Biological: Insulin; Biological: Glucagon

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

EXPERIMENTAL

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.

Drug: MK-0893 10 mg; Drug: MK-0893 40 mg; Drug: MK-0893 200 mg; Biological: Sandostatine®; Biological: Insulin; Biological: Glucagon

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

EXPERIMENTAL

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.

Drug: MK-0893 200 mg; Drug: MK-0893 1000 mg; Drug: Placebo; Biological: Sandostatine®; Biological: Insulin; Biological: Glucagon

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

EXPERIMENTAL

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.

Drug: MK-0893 200 mg; Drug: MK-0893 1000 mg; Drug: Placebo; Biological: Sandostatine®; Biological: Insulin; Biological: Glucagon

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

EXPERIMENTAL

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.

Drug: MK-0893 200 mg; Drug: MK-0893 1000 mg; Drug: Placebo; Biological: Sandostatine®; Biological: Insulin; Biological: Glucagon

Interventions

MK-0893 10 mg DRUG

MK-0893 10 mg administered orally in 240 mL of water

MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg; MK-0893 200 mg→placebo→MK-0893 10 mg; Placebo→MK-0893 10 mg→MK-0893 40 mg

MK-0893 40 mg DRUG

MK-0893 40 mg administered orally in 240 mL of water

MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg; MK-0893 40 mg→MK-0893 200 mg→placebo; Placebo→MK-0893 10 mg→MK-0893 40 mg

MK-0893 200 mg DRUG

MK-0893 200 mg administered orally in 240 mL of water

MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg; MK-0893 1000 mg→MK-0893 200 mg→placebo; MK-0893 200 mg→placebo→MK-0893 10 mg; MK-0893 200 mg→placebo→MK-0893 1000 mg; MK-0893 40 mg→MK-0893 200 mg→placebo; Placebo→MK-0893 1000 mg→MK-0893 200 mg

MK-0893 1000 mg DRUG

MK-0893 1000 mg administered orally in 240 mL of water

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

Placebo DRUG

Placebo administered orally in 240 mL of water

MK-0893 1000 mg→MK-0893 200 mg→placebo; MK-0893 200 mg→placebo→MK-0893 10 mg; MK-0893 200 mg→placebo→MK-0893 1000 mg; MK-0893 40 mg→MK-0893 200 mg→placebo; Placebo→MK-0893 10 mg→MK-0893 40 mg; Placebo→MK-0893 1000 mg→MK-0893 200 mg

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.

Also known as: Octreotide acetate

MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg; MK-0893 1000 mg→MK-0893 200 mg→placebo; MK-0893 200 mg→placebo→MK-0893 10 mg; MK-0893 200 mg→placebo→MK-0893 1000 mg; MK-0893 40 mg→MK-0893 200 mg→placebo; Placebo→MK-0893 10 mg→MK-0893 40 mg; Placebo→MK-0893 1000 mg→MK-0893 200 mg

Insulin BIOLOGICAL

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.

Also known as: Humuline Regular, Insulin for human injection

MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg; MK-0893 1000 mg→MK-0893 200 mg→placebo; MK-0893 200 mg→placebo→MK-0893 10 mg; MK-0893 200 mg→placebo→MK-0893 1000 mg; MK-0893 40 mg→MK-0893 200 mg→placebo; Placebo→MK-0893 10 mg→MK-0893 40 mg; Placebo→MK-0893 1000 mg→MK-0893 200 mg

Glucagon BIOLOGICAL

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.

Also known as: Glucagen

MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg; MK-0893 1000 mg→MK-0893 200 mg→placebo; MK-0893 200 mg→placebo→MK-0893 10 mg; MK-0893 200 mg→placebo→MK-0893 1000 mg; MK-0893 40 mg→MK-0893 200 mg→placebo; Placebo→MK-0893 10 mg→MK-0893 40 mg; Placebo→MK-0893 1000 mg→MK-0893 200 mg

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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®.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Interventions

N-((4-(1-(3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl)ethyl)phenyl)carbonyl)-beta-alanine; Octreotide; Insulin; Glucagon; Glucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Proglucagon; Glucagon-Like Peptides; Gastrointestinal Hormones

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2013
• First Posted: December 16, 2013
• Study Start: July 1, 2005
• Primary Completion: December 1, 2005
• Study Completion: December 1, 2005
• Last Updated: August 19, 2015

Record last verified: 2015-08