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)

Study Overview
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: MK-0893 10 mg
* Drug: MK-0893 40 mg
* Drug: MK-0893 200 mg
* Drug: MK-0893 1000 mg
* Drug: Placebo
* Biological: Sandostatine®
* Biological: Insulin
* Biological: Glucagon


Participation Criteria
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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®.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0893 40 mg→MK-0893 200 mg→placebo<br>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<br>* MK-0893 40 mg administered orally in 240 mL of water<br>Drug: MK-0893 200 mg<br>* MK-0893 200 mg administered orally in 240 mL of water<br>Drug: Placebo<br>* Placebo administered orally in 240 mL of water<br>Biological: Sandostatine®<br>* 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.<br>* Other names: Octreotide acetate;Biological: Insulin<br>* 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.<br>* Other names: Humuline Regular, Insulin for human injection;Biological: Glucagon<br>* 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.<br>* Other names: Glucagen;|
| Experimental: MK-0893 200 mg→placebo→MK-0893 10 mg<br>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<br>* MK-0893 10 mg administered orally in 240 mL of water<br>Drug: MK-0893 200 mg<br>* MK-0893 200 mg administered orally in 240 mL of water<br>Drug: Placebo<br>* Placebo administered orally in 240 mL of water<br>Biological: Sandostatine®<br>* 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.<br>* Other names: Octreotide acetate;Biological: Insulin<br>* 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.<br>* Other names: Humuline Regular, Insulin for human injection;Biological: Glucagon<br>* 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.<br>* Other names: Glucagen;|
| Experimental: Placebo→MK-0893 10 mg→MK-0893 40 mg<br>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<br>* MK-0893 10 mg administered orally in 240 mL of water<br>Drug: MK-0893 40 mg<br>* MK-0893 40 mg administered orally in 240 mL of water<br>Drug: Placebo<br>* Placebo administered orally in 240 mL of water<br>Biological: Sandostatine®<br>* 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.<br>* Other names: Octreotide acetate;Biological: Insulin<br>* 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.<br>* Other names: Humuline Regular, Insulin for human injection;Biological: Glucagon<br>* 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.<br>* Other names: Glucagen;|
| Experimental: MK-0893 10 mg→MK-0893 40 mg→MK-0893 200 mg<br>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<br>* MK-0893 10 mg administered orally in 240 mL of water<br>Drug: MK-0893 40 mg<br>* MK-0893 40 mg administered orally in 240 mL of water<br>Drug: MK-0893 200 mg<br>* MK-0893 200 mg administered orally in 240 mL of water<br>Biological: Sandostatine®<br>* 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.<br>* Other names: Octreotide acetate;Biological: Insulin<br>* 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.<br>* Other names: Humuline Regular, Insulin for human injection;Biological: Glucagon<br>* 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.<br>* Other names: Glucagen;|
| Experimental: Placebo→MK-0893 1000 mg→MK-0893 200 mg<br>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<br>* MK-0893 200 mg administered orally in 240 mL of water<br>Drug: MK-0893 1000 mg<br>* MK-0893 1000 mg administered orally in 240 mL of water<br>Drug: Placebo<br>* Placebo administered orally in 240 mL of water<br>Biological: Sandostatine®<br>* 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.<br>* Other names: Octreotide acetate;Biological: Insulin<br>* 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.<br>* Other names: Humuline Regular, Insulin for human injection;Biological: Glucagon<br>* 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.<br>* Other names: Glucagen;|
| Experimental: MK-0893 200 mg→placebo→MK-0893 1000 mg<br>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<br>* MK-0893 200 mg administered orally in 240 mL of water<br>Drug: MK-0893 1000 mg<br>* MK-0893 1000 mg administered orally in 240 mL of water<br>Drug: Placebo<br>* Placebo administered orally in 240 mL of water<br>Biological: Sandostatine®<br>* 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.<br>* Other names: Octreotide acetate;Biological: Insulin<br>* 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.<br>* Other names: Humuline Regular, Insulin for human injection;Biological: Glucagon<br>* 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.<br>* Other names: Glucagen;|
| Experimental: MK-0893 1000 mg→MK-0893 200 mg→placebo<br>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<br>* MK-0893 200 mg administered orally in 240 mL of water<br>Drug: MK-0893 1000 mg<br>* MK-0893 1000 mg administered orally in 240 mL of water<br>Drug: Placebo<br>* Placebo administered orally in 240 mL of water<br>Biological: Sandostatine®<br>* 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.<br>* Other names: Octreotide acetate;Biological: Insulin<br>* 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.<br>* Other names: Humuline Regular, Insulin for human injection;Biological: Glucagon<br>* 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.<br>* Other names: Glucagen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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