Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to determine the safety and effectiveness of an investigational drug in patients with Type 2 Diabetes Mellitus.
Interventions
DRUGComparator: sitagliptin 100 mg
sitagliptin 100 mg oral tablet once daily for 54 weeks
DRUGComparator: sitagliptin 200 mg
sitagliptin 200 mg (2- 100 mg oral tablets) once daily for 54 weeks
DRUGComparator: placebo
placebo oral tablet once daily during Phase A (Weeks 0-18)
pioglitazone 30 mg oral tablet once daily during Phase B (Weeks 18-54)
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients at least 18 years of age and not older than 75 who have a specific type of diabetes called Type 2 Diabetes Mellitus
Exclusion criteria
* Younger than 18 years of age or older than 75 * Any condition, which in the opinion of the investigator, may not be in the patient's best interest to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in A1C at Week 18 | Weeks 0-18 | Hemoglobin A1C (A1C) is measured as percent. Thus this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FPG at Week 18 | Weeks 0-18 | The change from baseline reflects the Week 18 Fasting Plasma Glucose (FPG) minus the Week 0 FPG. |
| Change From Baseline in A1C at Week 54 | Weeks 0-54 | A1C is measured as percent. Thus this change from baseline reflects the Week 54 A1C percent minus the Week 0 A1C percent. |
| Change From Baseline in FPG at Week 54 | Weeks 0-54 | The change from baseline reflects the Week 54 FPG minus the Week 0 FPG. |
Participant flow
Recruitment details
First Patient In: 15-Oct-2004. Last Patient Last Visit: 28-Apr-2006. 60 medical clinics in the United States (US), 37 in 4 countries in Europe, and 17 in 5 countries in the rest of the world.
Pre-assignment details
Patients 18-75 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control (Hemoglobin A1C ≥7% and ≤10.0%) on diet and exercise alone were eligible to enter the study.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg The Sitagliptin 100 mg got 1 sitagliptin 100 mg tablet and 1 sitagliptin matching placebo tablet once daily Weeks 0-54 and pioglitazone placebo once daily in Weeks 18-54. | 205 |
| Sitagliptin 200 mg The Sitagliptin 200 mg got 2 sitagliptin 100 mg tablets once daily Weeks 0-54 and pioglitazone placebo once daily in Weeks 18-54. | 206 |
| Placebo/Pioglitazone The Placebo/Pioglitazone got 2 sitagliptin matching placebo tablets once daily in Weeks 0- 54 and pioglitazone 30 mg/day once daily in Weeks 18-54. | 110 |
| Total | 521 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 9 | 6 |
| Overall Study | Lack of Efficacy | 11 | 15 | 8 |
| Overall Study | Lost to Follow-up | 3 | 5 | 6 |
| Overall Study | Other | 3 | 3 | 1 |
| Overall Study | Patient Moved | 2 | 1 | 1 |
| Overall Study | Protocol specified discontinuation | 1 | 3 | 0 |
| Overall Study | Protocol Violation | 8 | 5 | 3 |
| Overall Study | Withdrawal by Subject | 14 | 21 | 5 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg | Sitagliptin 200 mg | Placebo/Pioglitazone | Total |
|---|---|---|---|---|
| Age, Continuous | 54.5 years STANDARD_DEVIATION 10 | 55.4 years STANDARD_DEVIATION 9.2 | 55.5 years STANDARD_DEVIATION 10.1 | 55.1 years STANDARD_DEVIATION 9.7 |
| Hemoglobin A1C (A1C) | 8.0 Percent STANDARD_DEVIATION 0.8 | 8.1 Percent STANDARD_DEVIATION 0.9 | 8.0 Percent STANDARD_DEVIATION 0.9 | 8.1 Percent STANDARD_DEVIATION 0.9 |
| Race/Ethnicity, Customized Asian | 8 participants | 7 participants | 5 participants | 20 participants |
| Race/Ethnicity, Customized Black | 16 participants | 11 participants | 12 participants | 39 participants |
| Race/Ethnicity, Customized Hispanic | 37 participants | 39 participants | 22 participants | 98 participants |
| Race/Ethnicity, Customized Other | 2 participants | 3 participants | 3 participants | 8 participants |
| Race/Ethnicity, Customized White | 142 participants | 146 participants | 68 participants | 356 participants |
| Sex: Female, Male Female | 95 Participants | 102 Participants | 41 Participants | 238 Participants |
| Sex: Female, Male Male | 110 Participants | 104 Participants | 69 Participants | 283 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 | 70 / 205 | 55 / 206 | 37 / 110 |
| serious Total, serious adverse events | 15 / 205 | 12 / 206 | 10 / 110 |
Outcome results
Primary
Change From Baseline in A1C at Week 18
Hemoglobin A1C (A1C) is measured as percent. Thus this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.
Time frame: Weeks 0-18
Population: All Patients Treated included those with ≥1 dose of study therapy, had a baseline and ≥1 post-baseline value. For those with no data at Week 18, last post-baseline observation was carried forward. Data after initiation of glycemic rescue were considered missing. Analysis adjusted for baseline values and prior antihyperglycemic therapy status.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in A1C at Week 18 | -0.48 percent |
| Sitagliptin 200 mg | Change From Baseline in A1C at Week 18 | -0.36 percent |
| Placebo/Pioglitazone | Change From Baseline in A1C at Week 18 | 0.12 percent |
p-value: <0.00195% CI: [-0.82, -0.39]ANCOVA
p-value: <0.00195% CI: [-0.7, -0.26]ANCOVA
Secondary
Change From Baseline in A1C at Week 54
A1C is measured as percent. Thus this change from baseline reflects the Week 54 A1C percent minus the Week 0 A1C percent.
Time frame: Weeks 0-54
Population: All Patients Treated included patients who received at least 1 dose of study therapy post-Week 18, a baseline value and ≥1 post-Week 18 value for this outcome. The last post- Week 18 observed measurement was carried forward to Week 54 for patients with no data at Week 54. Data after initiation of glycemic rescue were considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in A1C at Week 54 | -0.28 percent |
| Sitagliptin 200 mg | Change From Baseline in A1C at Week 54 | -0.19 percent |
| Placebo/Pioglitazone | Change From Baseline in A1C at Week 54 | -0.87 percent |
Secondary
Change From Baseline in FPG at Week 18
The change from baseline reflects the Week 18 Fasting Plasma Glucose (FPG) minus the Week 0 FPG.
Time frame: Weeks 0-18
Population: All Patients Treated included patients who received at least 1 dose of study therapy, and had a baseline value and ≥1 post-baseline value for this outcome. The last post-baseline observed measurement was carried forward to Week 18 for patients with no data at Week 18. Data after initiation of glycemic rescue were considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in FPG at Week 18 | -12.7 mg/dL |
| Sitagliptin 200 mg | Change From Baseline in FPG at Week 18 | -9.9 mg/dL |
| Placebo/Pioglitazone | Change From Baseline in FPG at Week 18 | 7.0 mg/dL |
p-value: <0.00295% CI: [-27.6, -6.1]ANCOVA
p-value: <0.00195% CI: [-30.5, -8.9]ANCOVA
Secondary
Change From Baseline in FPG at Week 54
The change from baseline reflects the Week 54 FPG minus the Week 0 FPG.
Time frame: Weeks 0-54
Population: All Patients Treated included patients who received at least 1 dose of study therapy 1 post-Week 18, a baseline value and ≥1 post-Week 18 value for this outcome. The last post- Week 18 observed measurement was carried forward to Week 54 for patients with no data at Week 54. Data after initiation of glycemic rescue were considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg | Change From Baseline in FPG at Week 54 | -5.5 mg/dL |
| Sitagliptin 200 mg | Change From Baseline in FPG at Week 54 | -0.7 mg/dL |
| Placebo/Pioglitazone | Change From Baseline in FPG at Week 54 | -28.0 mg/dL |