Type 2 Diabetes Mellitus
Conditions
Brief summary
A study to assess the safety and efficacy of the addition of sitagliptin compared to placebo in patients with Type 2 Diabetes Mellitus who have inadequate glycemic control on metformin.
Interventions
All participants will receive placebo tablets two weeks prior to treatment period. Participants will receive sitagliptin phosphate 100 mg tablets once daily (q.d.) and continue on stable dose of metformin therapy (500 or 850 mg twice daily). Treatment period of 24 weeks.
DRUGComparator: Placebo
All participants will receive placebo tablets two weeks prior to treatment period. Participants will receive sitagliptin phosphate placebo tablets q.d. and continue on stable dose of metformin therapy (500 or 850 mg twice daily). Treatment period of 24 weeks.
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 78 Years
Healthy volunteers
No
Inclusion criteria
* 18 - 78 years of age * Currently on metformin monotherapy
Exclusion criteria
* History of Type 1 diabetes mellitus or ketoacidosis * Currently on a weight loss program and not in the maintenance phase or has started on a weight loss medication within the last 8 weeks * Has undergone surgery requiring general anesthesia within the past 4 weeks or has planned major surgery * Currently participating in a study or has participated in a study with or without an investigational compound or device within the past 12 weeks * History of active liver disease such as chronic active hepatitis B or C, cirrhosis or symptomatic gallbladder disease * HIV positive * Pregnant, breast-feeding or planning to become pregnant during the study * User of recreational or illicit drugs or has a recent history (within the past year) of drug or alcohol abuse or dependence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | Baseline and Week 24 | A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1000 mg/Day | Baseline and Week 24 | A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. |
| Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1700 mg/Day | Baseline and Week 24 | A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. |
| Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Baseline and Week 24 | Change from baseline at Week 24 is defined as Week 24 minus Week 0. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Sitagliptin phosphate 100 mg tablets once daily (q.d.) and a stable dose of metformin therapy for 24 weeks. | 197 |
| Placebo Placebo tablets q.d. and a stable dose of metformin therapy for 24 weeks. | 198 |
| Total | 395 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Clinical adverse event | 9 | 3 |
| Overall Study | Laboratory adverse event | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Other reason | 2 | 2 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Subject moved | 4 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 5 |
Baseline characteristics
| Characteristic | Sitagliptin | Total | Placebo |
|---|---|---|---|
| 2-hour Post-meal Glucose | 258.0 mg/dL STANDARD_DEVIATION 58 | 258.3 mg/dL STANDARD_DEVIATION 60.6 | 258.7 mg/dL STANDARD_DEVIATION 63.2 |
| Age, Continuous | 54.1 years STANDARD_DEVIATION 9 | 54.6 years STANDARD_DEVIATION 9.4 | 55.1 years STANDARD_DEVIATION 9.8 |
| Fasting Plasma Glucose | 173.4 mg/dL STANDARD_DEVIATION 39.3 | 173.7 mg/dL STANDARD_DEVIATION 39.6 | 173.9 mg/dL STANDARD_DEVIATION 40 |
| Hemoglobin A1c (HbA1c) | 8.5 Percent STANDARD_DEVIATION 0.9 | 8.5 Percent STANDARD_DEVIATION 0.9 | 8.5 Percent STANDARD_DEVIATION 0.9 |
| Region of Enrollment China | 197 participants | 395 participants | 198 participants |
| Sex: Female, Male Female | 105 Participants | 195 Participants | 90 Participants |
| Sex: Female, Male Male | 92 Participants | 200 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 197 | 13 / 198 |
| serious Total, serious adverse events | 7 / 197 | 5 / 198 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (A1C) at Week 24
A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and Week 24
Population: Full Analysis Set (defined as a subset of all randomized participants who received at least one dose of double-blind study medication, and had both a baseline \[randomization\] measurement and a post-randomization measurement) using last observation carried forward for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | -1.02 Percent | 95% Confidence Interval 0.99 |
| Placebo | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | -0.14 Percent | 95% Confidence Interval 1.22 |
p-value: <0.001ANCOVA
Secondary
Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Time frame: Baseline and Week 24
Population: Full Analysis Set (defined as a subset of all randomized participants who received at least one dose of double-blind study medication, and had both a baseline \[randomization\] measurement and a post-randomization measurement) using last observation carried forward for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | -43.4 mg/dL | 95% Confidence Interval 57.3 |
| Placebo | Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24 | -10.0 mg/dL | 95% Confidence Interval 60 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
Time frame: Baseline and Week 24
Population: Full Analysis Set (defined as a subset of all randomized participants who received at least one dose of double-blind study medication, and had both a baseline \[randomization\] measurement and a post-randomization measurement) using last observation carried forward for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | -20.3 mg/dL | 95% Confidence Interval 39.1 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | 0.5 mg/dL | 95% Confidence Interval 40.1 |
Secondary
Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1000 mg/Day
A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and Week 24
Population: Full Analysis Set (defined as a subset of all randomized participants who received at least one dose of double-blind study medication, and had both a baseline \[randomization\] measurement and a post-randomization measurement) using last observation carried forward for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1000 mg/Day | -0.84 Percent | 95% Confidence Interval 1.09 |
| Placebo | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1000 mg/Day | -0.01 Percent | 95% Confidence Interval 1.31 |
Secondary
Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1700 mg/Day
A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Time frame: Baseline and Week 24
Population: Full Analysis Set (defined as a subset of all randomized participants who received at least one dose of double-blind study medication, and had both a baseline \[randomization\] measurement and a post-randomization measurement) using last observation carried forward for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1700 mg/Day | -1.14 Percent | 95% Confidence Interval 0.88 |
| Placebo | Change From Baseline in Hemoglobin A1c (A1C) at Week 24 for Participants on Metformin 1700 mg/Day | -0.21 Percent | 95% Confidence Interval 1.12 |