Type 2 Diabetes Mellitus
Conditions
Brief summary
This study will assess the safety, tolerability, pharmacokinetics, and glucose lowering activity of MK-8245 in participants with type 2 diabetes. The primary hypothesis of the study is that after 4 weeks of treatment, MK-8245 produces a greater reduction in 24 hour weighted mean glucose (WMG) from baseline than placebo.
Interventions
DRUGMK-8245
MK-8245 50 mg twice daily for 28 days
DRUGComparator: placebo
matching placebo to MK-8245 twice daily for 28 days
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject has a diagnosis of type 2 diabetes and is being treated with diet and exercise alone, a single oral anti-hyperglycemic agent or a combination of two oral anti-hyperglycemic agents * Subject is willing to follow a weight-maintaining diet and exercise program during the study * Subject is a nonsmoker or is willing to limit smoking to 10 cigarettes per day while in the clinical research unit
Exclusion criteria
* Subject has a history of stroke, chronic seizures, or major neurological disorder * Subject has a history of cancer, except certain skin and cervical cancers or cancer that was successfully treated 10 or more years prior to screening * Subject has a history of type 1 diabetes * Subject has used contact lenses within the last 6 months * Subject has used any lipid-lowering therapy in the last 3 months, except statins, Zetia, or Vytorin * Subject has more than 3 alcoholic beverages per day * Subject has more than 6 servings of caffeine a day * Subject has participated in a previous MK8245 study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 24-hour Weighted Mean Glucose (WMG) | Baseline and Day 28 | The 24-hour WMG is derived from multiple glucose values collected during both fasting and post-meal periods. A weighted rather than a simple mean is used to avoid overrepresentation of post-meal glucose values. Blood samples for glucose were collected immediately prior to, and after each meal, and overnight and fasting one hour pre-dose. |
| Number of Participants Who Experienced Serious or Non-serious Adverse Events | Up to Day 31 | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. A serious AE is any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. |
| Number of Participants Discontinuing Study Drug Due to an AE | Up to Day 28 | An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. |
Participant flow
Recruitment details
This was a multicenter study in 5 clinical centers in the United States.
Participants by arm
| Arm | Count |
|---|---|
| MK-8245 100 mg MK-8245, 50 mg, twice daily for 28 days | 28 |
| Placebo Placebo to MK-8245, twice daily for 28 days | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Consistently high glucose values | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Positive drug screen | 0 | 1 |
Baseline characteristics
| Characteristic | MK-8245 100 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.7 Years STANDARD_DEVIATION 8.53 | 52.7 Years STANDARD_DEVIATION 7.3 | 53.7 Years STANDARD_DEVIATION 7.93 |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 28 | 8 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Change From Baseline in the 24-hour Weighted Mean Glucose (WMG)
The 24-hour WMG is derived from multiple glucose values collected during both fasting and post-meal periods. A weighted rather than a simple mean is used to avoid overrepresentation of post-meal glucose values. Blood samples for glucose were collected immediately prior to, and after each meal, and overnight and fasting one hour pre-dose.
Time frame: Baseline and Day 28
Population: All participants who were compliant with the study procedures and have available data from at least one treatment were included in the primary analysis dataset.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MK-8245 100 mg | Change From Baseline in the 24-hour Weighted Mean Glucose (WMG) | 11.0 mg/dL | Standard Deviation 27.6 |
| Placebo | Change From Baseline in the 24-hour Weighted Mean Glucose (WMG) | -4.4 mg/dL | Standard Deviation 31.7 |
p-value: 0.08390% CI: [-29.87, -0.82]Least Squares Means Difference
Primary
Number of Participants Discontinuing Study Drug Due to an AE
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Time frame: Up to Day 28
Population: All participants who received at least one dose of the investigational drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8245 100 mg | Number of Participants Discontinuing Study Drug Due to an AE | 2 Participants |
| Placebo | Number of Participants Discontinuing Study Drug Due to an AE | 1 Participants |
Primary
Number of Participants Who Experienced Serious or Non-serious Adverse Events
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. A serious AE is any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: Up to Day 31
Population: All participants who received at least one dose of the investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-8245 100 mg | Number of Participants Who Experienced Serious or Non-serious Adverse Events | Serious Adverse Events | 0 Participants |
| MK-8245 100 mg | Number of Participants Who Experienced Serious or Non-serious Adverse Events | Non-Serious Adverse Events | 16 Participants |
| Placebo | Number of Participants Who Experienced Serious or Non-serious Adverse Events | Serious Adverse Events | 0 Participants |
| Placebo | Number of Participants Who Experienced Serious or Non-serious Adverse Events | Non-Serious Adverse Events | 10 Participants |