A Study to Assess the Safety, Tolerability and Glucose-Lowering Efficacy of MK-0893 in Participants With Type 2 Diabetes Mellitus (MK-0893-005)

Study Overview
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Brief Summary
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This study will assess the safety, tolerability and glucose-lowering efficacy of MK-0893 in participants with type 2 diabetes mellitus. The primary hypothesis is that MK-0893 will reduce 24-hour weighted mean glucose (WMG) significantly more than placebo.

Official Title
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A Multi-Center, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel Panel Study to Assess the Safety, Tolerability and Glucose-Lowering Efficacy of MK-0893 in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: MK-0893
* Drug: Metformin
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Not currently on antihyperglycemic agent (AHA) or AHA monotherapy (not to include treatment with insulin or thiazolidinediones [i.e., peroxisome proliferator activated receptor-gamma, PPARγ agents]) male or a female of non-childbearing potential. Women must be postmenopausal or premenopausal and documented surgically sterilized A body mass index (BMI) that is > 20 and ≤ 40 kg/m2 Exclusion Criteria: History of type 1 diabetes or assessed by the investigator as possibly having type 1 diabetes History of ketoacidosis; clinically unstable or rapidly progressive diabetic retinopathy, nephropathy, neuropathy Treatment for diabetes within 3 months of study participation with combination anti-hyperglycemic therapy, insulin or thiazolidinediones (e.g., rosiglitazone or pioglitazone) oral corticosteroid medications within 2 weeks prior to study participation, or requires digoxin, warfarin, warfarin-like anticoagulants, theophylline, anti-dysrhythmic or anti-seizure medications, immunosuppressants, or anti-neoplastic agents, or herbal remedies History of acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) History of gastrointestinal problems or disorders or extensive bowel or gastric surgery History of significant or unstable cardiovascular disease History of neoplastic disease History of hepatic disease History of seizures, epilepsy or other neurologic disease History of myelodysplastic or pre-leukemic disorders or other severe hematological disorder

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-0893 (40 mg)<br>MK-0893 40-mg q.d. (quaque die, once daily) group will receive MK-0893 40-mg tablets (after loading dose with 160 mg) and matching placebo to metformin and matching placebo to MK-0893. | Drug: MK-0893<br>* 10 mg and 100 mg tablets<br>Drug: Placebo<br>* Placebo tablets matching MK-0893<br>Drug: Placebo<br>* Placebo tablets matching metformin<br>|
| Experimental: MK-0893 (120 mg)<br>MK-0893 at 120 mg q.d. group will receive MK-0893 120 mg q.d. tablets (after loading dose of 500 mg on Day 1) and matching placebo tablets to metformin and matching placebo to MK-0893 | Drug: MK-0893<br>* 10 mg and 100 mg tablets<br>Drug: Placebo<br>* Placebo tablets matching MK-0893<br>Drug: Placebo<br>* Placebo tablets matching metformin<br>|
| Active Comparator: Metformin (2000 mg)<br>Metformin taken orally, 500 mg tablets, Day 1 to Day 6: 500 mg b.i.d. (bis in die, twice daily), Day 7 to Day 13: 1000 mg in the morning and 500 mg in the evening, and Day 14 to Day 28: 1000 mg. b.i.d. and matching placebo to MK-0893. | Drug: Metformin<br>* 500 mg metformin tablets<br>* Other names: Riomet;Drug: Placebo<br>* Placebo tablets matching MK-0893<br>|
| Placebo Comparator: Placebo<br>Placebo tablets matching the MK-0893 and placebo tablets matching metformin. | Drug: Placebo<br>* Placebo tablets matching MK-0893<br>Drug: Placebo<br>* Placebo tablets matching metformin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | Blood samples were collected 30 minutes prior to all meals, and 15, 30, 60, 90, 120, 180 minutes post-meal, then and at midnight, 3 AM, and the next morning at 6:30 AM and 7:30 AM. A 24-hour weighted mean glucose (WMG) was determined by averaging multiple plasma glucose measurements over a 24-hour period. | Baseline and Week 4 | 
| Number of Participants Experiencing an Adverse Event (AE) | An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. | Up to 42 days | 
| Number of Participants Discontinuing Study Treatment Due to an AE | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Plasma Glucose levels were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value. | Baseline and Week 4 | 
| Change From Baseline in Fructosamine at Week 4 | Fructosamine levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value. | Baseline and Week 4 | 
| Change From Baseline in Fasting C-peptide at Week 4 | Fasting C-peptide levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value. | Baseline and Week 4 | 
| Change From Baseline in Fasting Insulin at Week 4 | Fasting insulin levels in the blood were measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value. | Baseline and Week 4 | 
| Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4 | 2-hour post-prandial glucose excursion is the change in glucose concentration in the blood 2 hours after a meal. Change from baseline in 2-hour post-prandial glucose excursion at Week 4 is defined as Week 4 minus baseline. | Baseline and Week 4 | 
| Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4 | Blood samples collected for glucose 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour AUC for Glucose was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value. | Baseline and Week 4 | 
| Change From Baseline in 3-hour AUC for C-peptide at Week 4 | Blood samples were collected for C-peptide 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour AUC for C-peptide was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value. | Baseline and Week 4 | 
| Change From Baseline in 3-hour Insulin Total AUC at Week 4 | Blood samples were collected for insulin 30 minutes prior to the breakfast meal and 15, 30, 60, 90, 120, 180 minutes post-meal. AUC is a measure of the amount of drug in the blood over time. 3-hour Insulin Total AUC was measured at Baseline and at Week 4. The change from baseline was defined as the Week 4 value minus the Baseline value. | Baseline and Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, Metformin, Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Therapeutic Uses, Pharmacologic Actions