Diabetes Mellitus, Type 2
Conditions
Brief summary
A study to test the pharmacokinetics after twice daily administration of MK-0941 or placebo in subjects with type 2 diabetes who have inadequate control on metformin.
Interventions
DRUGMK-0941
Part 1 (in house): MK-0941 twice daily on Days 1 through 13 before breakfast and dinner with 240 mL water. The starting dose on Day 1 was 10 mg tablets twice daily and titrated to a maximum dose of 60 mg twice daily through Day 9. The Day 9 dose was maintained throughout Day 13. Part 2 (at home): participants continued treatment for an additional 14 days with MK-0941 60 mg tablets (or maximum dose achieved in Part 1) twice daily, before meals with 240 mL of water.
DRUGComparator: Placebo
Part 1 (in house): placebo twice daily on Days 1 through 13 before breakfast and dinner with 240 mL water. Part 2 (at home): participants continued treatment for an additional 14 days with placebo twice daily, before meals with 240 mL of water.
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Subject has a BMI \< 42 kg/m2 * Subject is taking \>1500 mg metformin per day for at least 8 weeks * Subject has HbA1c value of 7.0% and \< 11% at screening * Subject is willing to follow AHA weight maintaining diet and exercise program * Subject is a nonsmoker for at least 6 months
Exclusion criteria
* Subject has type 1 diabetes * Subject has a history of stroke or chronic seizure * Subject has a history of neoplastic disease * Subject has a history of gastrointestinal, cardiovascular, blood, liver kidney, respiratory, immunological or genitourinary disorders or diseases * Subject is currently taking 2 or more diabetes medications * Subject has glaucoma or is blind * If female, subject is pregnant or breastfeeding * Subject consumes \> 3 alcoholic beverages per day * Subject has had major surgery or has donated blood in the last 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Clinical Adverse Experience | 2 months | An adverse experience was defined as any unfavorable and unintended change in the structure or function of the body temporally associated with the use of study drug. Adverse experiences were collected using Medical Dictionary for Regulatory Activities (MedDRA) version 13.0. |
| Number of Participants With Any Laboratory Adverse Experience | 2 months | Laboratory adverse experiences were those related to changes in hematology, fasted blood chemistry, or urinalysis laboratory results. Adverse experiences were collected using MedDRA version 13.0. |
| Change From Baseline to Day 13 in Weighted Mean Plasma Glucose Concentration | Baseline (predose Day 1) to Day 13 | Weighted mean plasma glucose concentration was calculated as the 24-hour area under the plasma concentration-time curve divided by 24 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-0941 Part 1 (in house): MK-0941 twice daily on Days 1 through 13 before breakfast and dinner with 240 mL water. The starting dose on Day 1 was 10 mg tablets twice daily and titrated to a maximum dose of 60 mg twice daily through Day 9. The Day 9 dose was maintained throughout Day 13. Part 2 (at home): participants continued treatment for an additional 14 days with MK-0941 60 mg tablets (or maximum dose achieved in Part 1) twice daily, before meals with 240 mL of water. | 22 |
| Placebo Part 1 (in house): placebo twice daily on Days 1 through 13 before breakfast and dinner with 240 mL water. Part 2 (at home): participants continued treatment for an additional 14 days with placebo twice daily, before meals with 240 mL of water. | 22 |
| Total | 44 |
Baseline characteristics
| Characteristic | MK-0941 | Placebo | Total |
|---|---|---|---|
| Age, Customized 37 to 70 years | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 22 | 16 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Change From Baseline to Day 13 in Weighted Mean Plasma Glucose Concentration
Weighted mean plasma glucose concentration was calculated as the 24-hour area under the plasma concentration-time curve divided by 24
Time frame: Baseline (predose Day 1) to Day 13
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-0941 | Change From Baseline to Day 13 in Weighted Mean Plasma Glucose Concentration | Baseline | 196.4 mg/dL | Standard Deviation 47.6 |
| MK-0941 | Change From Baseline to Day 13 in Weighted Mean Plasma Glucose Concentration | Change from baseline to Day 13 | -56.4 mg/dL | Standard Deviation 33.9 |
| Placebo | Change From Baseline to Day 13 in Weighted Mean Plasma Glucose Concentration | Change from baseline to Day 13 | -15.6 mg/dL | Standard Deviation 30 |
| Placebo | Change From Baseline to Day 13 in Weighted Mean Plasma Glucose Concentration | Baseline | 194.6 mg/dL | Standard Deviation 35.3 |
Comparison: Difference (placebo minus MK-0941) in change from baseline to Day 13p-value: <0.00195% CI: [26.33, 55.32]Mixed Models Analysis
Primary
Number of Participants With Any Clinical Adverse Experience
An adverse experience was defined as any unfavorable and unintended change in the structure or function of the body temporally associated with the use of study drug. Adverse experiences were collected using Medical Dictionary for Regulatory Activities (MedDRA) version 13.0.
Time frame: 2 months
Population: All study participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0941 | Number of Participants With Any Clinical Adverse Experience | 18 participants |
| Placebo | Number of Participants With Any Clinical Adverse Experience | 16 participants |
Primary
Number of Participants With Any Laboratory Adverse Experience
Laboratory adverse experiences were those related to changes in hematology, fasted blood chemistry, or urinalysis laboratory results. Adverse experiences were collected using MedDRA version 13.0.
Time frame: 2 months
Population: All study participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-0941 | Number of Participants With Any Laboratory Adverse Experience | 3 participants |
| Placebo | Number of Participants With Any Laboratory Adverse Experience | 1 participants |