Type 2 Diabetes Mellitus
Conditions
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
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.
Interventions
DRUGPlacebo
Placebo tablets matching MK-0893
DRUGMK-0893
10 mg and 100 mg tablets
DRUGMetformin
500 mg metformin tablets
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | Baseline and 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) | Up to 42 days | 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 | Up to 28 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Insulin at Week 4 | Baseline and 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 | Baseline and 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 Fasting Plasma Glucose (FPG) | Baseline and Week 4 | 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 3-hour AUC for C-peptide at Week 4 | Baseline and 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 | Baseline and 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. |
| Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4 | Baseline and 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 Fructosamine at Week 4 | Baseline and 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 | Baseline and 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. |
Participant flow
Recruitment details
A total of 13 clinical sites were used in this study in the following countries: Austria, Germany, New Zealand, Russia, and the United States of America.
Participants by arm
| Arm | Count |
|---|---|
| MK-0893 (40 mg) MK-0893 40-mg, once daily | 19 |
| MK-0893 (120 mg) MK-0893, 120 mg, once daily | 18 |
| Metformin (2000 mg) Metformin, oral, 1000 mg, twice daily | 18 |
| Placebo Placebo | 19 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Unable to attend future visits | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MK-0893 (40 mg) | MK-0893 (120 mg) | Metformin (2000 mg) | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 54.5 Years STANDARD_DEVIATION 7.1 | 55.8 Years STANDARD_DEVIATION 6.8 | 54.7 Years STANDARD_DEVIATION 8.7 | 51.5 Years STANDARD_DEVIATION 9.3 | 54.1 Years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 12 Participants | 7 Participants | 36 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 6 Participants | 12 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 19 | 7 / 18 | 9 / 18 | 8 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 | 0 / 18 | 0 / 19 |
Outcome results
Primary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | -37.9 mg/dL |
| MK-0893 (120 mg) | Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | -65.7 mg/dL |
| Metformin (2000 mg) | Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | -38.1 mg/dL |
| Placebo | Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | -12.0 mg/dL |
p-value: <0.00195% CI: [-38.4, -13.3]ANCOVA
p-value: <0.00195% CI: [-66.1, -41.1]ANCOVA
p-value: <0.00195% CI: [-38.4, -13.6]ANCOVA
Primary
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.
Time frame: Up to 28 days
Population: Safety Population included all randomized participants who initiated study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0893 (40 mg) | Number of Participants Discontinuing Study Treatment Due to an AE | 0 Number of Participants |
| MK-0893 (120 mg) | Number of Participants Discontinuing Study Treatment Due to an AE | 1 Number of Participants |
| Metformin (2000 mg) | Number of Participants Discontinuing Study Treatment Due to an AE | 0 Number of Participants |
| Placebo | Number of Participants Discontinuing Study Treatment Due to an AE | 0 Number of Participants |
Primary
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.
Time frame: Up to 42 days
Population: Safety Population included all randomized participants who initiated study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0893 (40 mg) | Number of Participants Experiencing an Adverse Event (AE) | 3 Number of Participants |
| MK-0893 (120 mg) | Number of Participants Experiencing an Adverse Event (AE) | 7 Number of Participants |
| Metformin (2000 mg) | Number of Participants Experiencing an Adverse Event (AE) | 9 Number of Participants |
| Placebo | Number of Participants Experiencing an Adverse Event (AE) | 8 Number of Participants |
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4 | -10.5 mg/dL |
| MK-0893 (120 mg) | Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4 | -15.3 mg/dL |
| Metformin (2000 mg) | Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4 | -29.0 mg/dL |
| Placebo | Change From Baseline in 2-hour Post-prandial Glucose Excursion at Week 4 | -2.8 mg/dL |
p-value: 0.25395% CI: [-21.1, 5.6]ANCOVA
p-value: 0.0795% CI: [-26, 1]ANCOVA
p-value: <0.00195% CI: [-39.5, -12.8]ANCOVA
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4 | -128.8 mg hr/dL |
| MK-0893 (120 mg) | Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4 | -230.2 mg hr/dL |
| Metformin (2000 mg) | Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4 | -136.7 mg hr/dL |
| Placebo | Change From Baseline in 3-hour Area Under the Plasma Concentration Versus Time Curve (AUC) for Glucose at Week 4 | -39.0 mg hr/dL |
p-value: 0.00295% CI: [-145.6, -34]ANCOVA
p-value: <0.00195% CI: [-246.4, -135.9]ANCOVA
p-value: 0.00195% CI: [-152.4, -42.9]ANCOVA
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in 3-hour AUC for C-peptide at Week 4 | 1.0 ng hr/mL |
| MK-0893 (120 mg) | Change From Baseline in 3-hour AUC for C-peptide at Week 4 | -0.5 ng hr/mL |
| Metformin (2000 mg) | Change From Baseline in 3-hour AUC for C-peptide at Week 4 | -0.2 ng hr/mL |
| Placebo | Change From Baseline in 3-hour AUC for C-peptide at Week 4 | -0.1 ng hr/mL |
p-value: 0.40895% CI: [-1.5, 3.7]ANCOVA
p-value: 0.74195% CI: [-3.1, 2.2]ANCOVA
p-value: 0.90695% CI: [-2.8, 2.5]ANCOVA
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in 3-hour Insulin Total AUC at Week 4 | 5.3 µIU hr/mL |
| MK-0893 (120 mg) | Change From Baseline in 3-hour Insulin Total AUC at Week 4 | 6.1 µIU hr/mL |
| Metformin (2000 mg) | Change From Baseline in 3-hour Insulin Total AUC at Week 4 | 1.2 µIU hr/mL |
| Placebo | Change From Baseline in 3-hour Insulin Total AUC at Week 4 | 7.8 µIU hr/mL |
p-value: 0.85795% CI: [-30.4, 25.3]ANCOVA
p-value: 0.90695% CI: [-30.3, 26.9]ANCOVA
p-value: 0.6395% CI: [-34, 20.8]ANCOVA
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in Fasting C-peptide at Week 4 | 0.1 ng/mL | 95% Confidence Interval 0.4 |
| MK-0893 (120 mg) | Change From Baseline in Fasting C-peptide at Week 4 | -0.3 ng/mL | 95% Confidence Interval 0.3 |
| Metformin (2000 mg) | Change From Baseline in Fasting C-peptide at Week 4 | -0.1 ng/mL | 95% Confidence Interval 0.3 |
| Placebo | Change From Baseline in Fasting C-peptide at Week 4 | -0.0 ng/mL | 95% Confidence Interval 0.2 |
p-value: 0.75195% CI: [-0.7, 0.9]ANCOVA
p-value: 0.58195% CI: [-1, 0.6]ANCOVA
p-value: 0.91895% CI: [-0.8, 0.8]ANCOVA
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in Fasting Insulin at Week 4 | NA μIU/mL |
| MK-0893 (120 mg) | Change From Baseline in Fasting Insulin at Week 4 | NA μIU/mL |
| Metformin (2000 mg) | Change From Baseline in Fasting Insulin at Week 4 | NA μIU/mL |
| Placebo | Change From Baseline in Fasting Insulin at Week 4 | NA μIU/mL |
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in Fasting Plasma Glucose (FPG) | -32.5 mg/dL |
| MK-0893 (120 mg) | Change From Baseline in Fasting Plasma Glucose (FPG) | -57.7 mg/dL |
| Metformin (2000 mg) | Change From Baseline in Fasting Plasma Glucose (FPG) | -22.8 mg/dL |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) | -14.1 mg/dL |
p-value: 0.0495% CI: [-35.7, -0.9]ANCOVA
p-value: <0.00195% CI: [-60.9, -26.3]ANCOVA
p-value: 0.3295% CI: [-25.7, 8.5]ANCOVA
Secondary
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.
Time frame: Baseline and Week 4
Population: Completers Population was used for all efficacy analyses, and required that a participant took at least one dose of study therapy, had a baseline measurement, and had a post-randomization measurement in the treatment period at Week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0893 (40 mg) | Change From Baseline in Fructosamine at Week 4 | NA mg/dL |
| MK-0893 (120 mg) | Change From Baseline in Fructosamine at Week 4 | NA mg/dL |
| Metformin (2000 mg) | Change From Baseline in Fructosamine at Week 4 | NA mg/dL |
| Placebo | Change From Baseline in Fructosamine at Week 4 | NA mg/dL |