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)

NCT ID: NCT02012166

Last Updated: 2015-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2005-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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MK-0893 40 mg→MK-0893 200 mg→placebo

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.

Group Type EXPERIMENTAL

MK-0893 40 mg

Intervention Type DRUG

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

MK-0893 200 mg

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo administered orally in 240 mL of water

Sandostatine®

Intervention Type 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.

Insulin

Intervention Type 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.

Glucagon

Intervention Type 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.

MK-0893 200 mg→placebo→MK-0893 10 mg

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.

Group Type EXPERIMENTAL

MK-0893 10 mg

Intervention Type DRUG

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

MK-0893 200 mg

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo administered orally in 240 mL of water

Sandostatine®

Intervention Type 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.

Insulin

Intervention Type 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.

Glucagon

Intervention Type 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.

Placebo→MK-0893 10 mg→MK-0893 40 mg

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.

Group Type EXPERIMENTAL

MK-0893 10 mg

Intervention Type DRUG

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

MK-0893 40 mg

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo administered orally in 240 mL of water

Sandostatine®

Intervention Type 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.

Insulin

Intervention Type 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.

Glucagon

Intervention Type 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.

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

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.

Group Type EXPERIMENTAL

MK-0893 10 mg

Intervention Type DRUG

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

MK-0893 40 mg

Intervention Type DRUG

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

MK-0893 200 mg

Intervention Type DRUG

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

Sandostatine®

Intervention Type 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.

Insulin

Intervention Type 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.

Glucagon

Intervention Type 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.

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

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.

Group Type EXPERIMENTAL

MK-0893 200 mg

Intervention Type DRUG

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

MK-0893 1000 mg

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo administered orally in 240 mL of water

Sandostatine®

Intervention Type 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.

Insulin

Intervention Type 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.

Glucagon

Intervention Type 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.

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

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.

Group Type EXPERIMENTAL

MK-0893 200 mg

Intervention Type DRUG

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

MK-0893 1000 mg

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo administered orally in 240 mL of water

Sandostatine®

Intervention Type 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.

Insulin

Intervention Type 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.

Glucagon

Intervention Type 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.

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

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.

Group Type EXPERIMENTAL

MK-0893 200 mg

Intervention Type DRUG

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

MK-0893 1000 mg

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Placebo administered orally in 240 mL of water

Sandostatine®

Intervention Type 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.

Insulin

Intervention Type 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.

Glucagon

Intervention Type 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.

Interventions

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MK-0893 10 mg

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

Intervention Type DRUG

MK-0893 40 mg

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

Intervention Type DRUG

MK-0893 200 mg

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

Intervention Type DRUG

MK-0893 1000 mg

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

Intervention Type DRUG

Placebo

Placebo administered orally in 240 mL of water

Intervention Type DRUG

Sandostatine®

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

Insulin

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

Glucagon

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.

Intervention Type BIOLOGICAL

Other Intervention Names

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Octreotide acetate Humuline Regular, Insulin for human injection Glucagen

Eligibility Criteria

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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®.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

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2005-002198-57

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0893-002

Identifier Type: -

Identifier Source: org_study_id

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