Back to resultsA Study to Assess the Safety, Tolerability and Glucose-Lowering Efficacy of MK-0893 in Participants With Type 2 Diabetes Mellitus (MK-0893-005)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MK-0893
Metformin
Placebo
Placebo
Sponsored by
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, Metformin
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Active Comparator
Placebo Comparator
Arm Label
MK-0893 (40 mg)
MK-0893 (120 mg)
Metformin (2000 mg)
Placebo
Arm Description
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.
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
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.
Placebo tablets matching the MK-0893 and placebo tablets matching metformin.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT02004886
First Posted
December 3, 2013
Last Updated
August 7, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02004886
Brief Title
A Study to Assess the Safety, Tolerability and Glucose-Lowering Efficacy of MK-0893 in Participants With Type 2 Diabetes Mellitus (MK-0893-005)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
August 11, 2006 (Actual)
Primary Completion Date
February 7, 2007 (Actual)
Study Completion Date
February 7, 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
5. Study Description
Brief Summary
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.
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, Metformin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
74 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-0893 (40 mg)
Arm Type
Experimental
Arm Description
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.
Arm Title
MK-0893 (120 mg)
Arm Type
Experimental
Arm Description
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
Arm Title
Metformin (2000 mg)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablets matching the MK-0893 and placebo tablets matching metformin.
Intervention Type
Drug
Intervention Name(s)
MK-0893
Intervention Description
10 mg and 100 mg tablets
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet
Intervention Description
500 mg metformin tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets matching MK-0893
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets matching metformin
Primary Outcome Measure Information:
Title
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4
Description
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.
Time Frame
Baseline and Week 4
Title
Number of Participants Experiencing an Adverse Event (AE)
Description
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.
Time Frame
Up to 42 days
Title
Number of Participants Discontinuing Study Treatment Due to an AE
Description
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.
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Change From Baseline in Fasting Plasma Glucose (FPG)
Description
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.
Time Frame
Baseline and Week 4
Title
Change From Baseline in Fructosamine at Week 4
Description
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.
Time Frame
Baseline and Week 4
Title
Change From Baseline in Fasting C-peptide at Week 4
Description
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.
Time Frame
Baseline and Week 4
Title
Change From Baseline in Fasting Insulin at Week 4
Description
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.
Time Frame
Baseline and Week 4
Title
Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4
Description
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.
Time Frame
Baseline and Week 4
Title
Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4
Description
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.
Time Frame
Baseline and Week 4
Title
Change From Baseline in 3-hour AUC for C-peptide at Week 4
Description
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.
Time Frame
Baseline and Week 4
Title
Change From Baseline in 3-hour Insulin Total AUC at Week 4
Description
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.
Time Frame
Baseline and Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=0893-005&kw=0893-005&tab=access
Learn more about this trial
A Study to Assess the Safety, Tolerability and Glucose-Lowering Efficacy of MK-0893 in Participants With Type 2 Diabetes Mellitus (MK-0893-005)
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