Type 2 Diabetes Mellitus
Conditions
Brief summary
A study to assess the safety and efficacy of MK8245 as monotherapy compared to placebo.
Interventions
DRUGMK8245 5 mg (twice a day) b.i.d.
All patients will receive placebo capsules 2 weeks prior to treatment period to be taken twice daily. Patients randomized to the 5 mg b.i.d. treatment group took 2 capsules of MK8245 2.5 mg in the morning and 2 capsules of MK8245 2.5 mg in the evening.
DRUGMK8245 50 mg b.i.d.
All patients will receive placebo capsules 2 weeks prior to treatment period to be taken twice daily. Patients randomized to the 50 mg b.i.d. treatment group took 2 capsules of MK8245 25 mg in the morning and 2 capsules of MK8245 25 mg in the evening.
DRUGPlacebo
All patients will receive placebo capsules 2 weeks prior to treatment period to be taken twice daily. Patients randomized to the placebo treatment group took 2 capsules of placebo matching MK8245 capsules in the morning and 2 placebo capsules matching MK8245 capsules in the evening.
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
* Have Type 2 Diabetes Mellitus * 18 to 65 years of age
Exclusion criteria
* History of Type 1 Diabetes or ketoacidosis * Have been treated with lipid lowering medications 4 weeks before starting the study * Have started on a weight loss program and not in the maintenance phase or have started weight loss medication within the last 12 weeks * Have had surgery in the last 30 days * History of active liver disease * History of coronary heart disease or congestive heart failure * Have had a stroke or transient ischemic neurological disorder in the past 6 months * Are Human Immunodeficiency Virus (HIV) Positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | Baseline and Week 4 | 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 to be collected immediately prior to (sample -10 minutes), and 0, 15, 30, 60, 90, 120, and 180 minutes after each meal, and overnight (at midnight, 3 AM, and 5 AM) and fasting at 7 AM. Patients were to be domiciled for approximately 26 hours at the site where standard meals were provided and physical activity monitored. |
Participant flow
Recruitment details
First Patient In:10-Feb-2009 Early Termination\*:11-Aug-2009 Last Patient Last Visit:19-Aug-2009 10 Centers Worldwide \*Study was terminated due to inability to recruit patients. Because it was not terminated for safety concerns, sites were to see patients for early termination visit at earliest convenience. The last patient was seen 19-Aug-2009.
Pre-assignment details
Patients 18-65 yrs not on antihyperglycemic agent (AHA) (A1C 7-10%),or single AHA (A1C 7-9.5%),or low dose dual AHA therapy (A1C 6.5-9.5%) with type 2 diabetes mellitus entered a 4-wk diet/exercise period (AHA wash-off if on AHA),after which,those with fasting glucose of 130-250 mg/dL were eligible for randomization (after a 2 wk pbo run-in period)
Participants by arm
| Arm | Count |
|---|---|
| MK8245 5 mg b.i.d. Patients randomized to the 5 mg (twice a day) b.i.d. treatment group took 2 capsules of MK8245 2.5 mg in the morning and 2 capsules of MK8245 2.5 mg in the evening. | 4 |
| MK8245 50 mg b.i.d. Patients randomized to the 50 mg b.i.d. treatment group took 2 capsules of MK8245 25 mg in the morning and 2 capsules of MK8245 25 mg in the evening. | 4 |
| Placebo Patients randomized to the placebo treatment group took 2 capsules of placebo matching MK8245 capsules in the morning and 2 placebo capsules matching MK8245 capsules in the evening. | 6 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | MK8245 5 mg b.i.d. | MK8245 50 mg b.i.d. | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 13.4 | 55.5 years STANDARD_DEVIATION 7.7 | 53.5 years STANDARD_DEVIATION 7.5 | 53.0 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black OR African American | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Multi-Racial | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 3 participants | 4 participants | 5 participants | 12 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 1 / 4 | 3 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 6 |
Outcome results
Primary
Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4
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 to be collected immediately prior to (sample -10 minutes), and 0, 15, 30, 60, 90, 120, and 180 minutes after each meal, and overnight (at midnight, 3 AM, and 5 AM) and fasting at 7 AM. Patients were to be domiciled for approximately 26 hours at the site where standard meals were provided and physical activity monitored.
Time frame: Baseline and Week 4
Population: The analysis population included all patients with a baseline value and Week 4 value for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK8245 5 mg b.i.d. | Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | -18.9 mg/dL | Standard Deviation 22.1 |
| MK8245 50 mg b.i.d. | Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | 18.7 mg/dL | Standard Deviation 6.7 |
| Placebo | Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Week 4 | -12.6 mg/dL | Standard Deviation 1.4 |