Type 2 Diabetes Mellitus
Conditions
Brief summary
The clinical study determines the safety and efficacy of MK0431 in patients with type 2 diabetes mellitus who have inadequate glycemic control on pioglitazone as monotherapy.
Interventions
DRUGsitagliptin phosphate
Sitagliptin (MK0431) 50 or 100 mg once daily for 52 weeks
DRUGComparator: sitagliptin phosphate (MK0431)
Sitagliptin (MK0431) 50 or 100 mg once daily for 40 weeks
pioglitazone once daily for 52 weeks
DRUGComparator: placebo (unspecified)
Placebo once daily for 12 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
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients Have Type 2 Diabetes Mellitus * On Diet/Exercise Therapy And Pioglitazone As Monotherapy
Exclusion criteria
* Patients Have Type 1 Diabetes Mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 12 | 12 Weeks | Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose at Week 12 | 12 Weeks | Change from baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 2 Hour Postprandial Glucose at Week 12 | 12 weeks | Change from baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication. |
| Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 52 | Week 52 (reflecting change from Week 0) for Sitagliptin/Sitagliptin group; Weeks 52 (reflecting change from Week 12) for Placebo/Sitagliptin group. | Change from the last value before receiving sitagliptin therapy: Week 0 for Sitagliptin/Sitagliptin group and Week 12 for the Placebo/Sitagliptin group. |
Participant flow
Recruitment details
Phase III. Date of first patient in: 22 August 2006. Date of last patient's last visit for Period I: 1 May 2007. Date of last patient's last visit for Period II: 5 February 2008. Number of randomized patients: 134. The study was conducted at 32 centers in Japan.
Pre-assignment details
Following a screening period of at least 4 weeks and a 2 or 8-week observation period, patients who were on pioglitazone monotherapy for at least 8 weeks and met all other entry criteria were randomized to receive: sitagliptin/sitagliptin or placebo/sitagliptin. The starting dose of sitagliptin was 50 mg for all patients.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin / Sitagliptin The Sitagliptin/Sitagliptin group includes data from all patients randomized to receive treatment with sitagliptin (Weeks 0-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40. | 66 |
| Placebo / Sitagliptin The Placebo/Sitagliptin group includes data from all patients randomized to receive the sequence of placebo (Weeks 0-12) / sitagliptin (Weeks 12-52) and pioglitazone (Weeks 0-52) orally once daily. Includes patients who received only sitagliptin 50 mg and those who started on sitagliptin 50 mg and whose dose was subsequently up-titrated to sitagliptin 100 mg orally once daily. Uptitration of sitagliptin dose was to occur for patients with FPG \>140 mg/dL at any time from Week 16 to Week 40 or HbA1c values \>7.0% at any time from Week 24 to Week 40. The sitagliptin dose was to have remained stable after Week 40. | 68 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period I - Double-blind (Weeks 0-12) | Adverse Event | 2 | 0 |
| Period I - Double-blind (Weeks 0-12) | Lack of Efficacy | 0 | 1 |
| Period I - Double-blind (Weeks 0-12) | No improvement in hyperglycemia | 1 | 0 |
| Period II - Open-label (Weeks 12-52) | Adverse Event | 3 | 0 |
| Period II - Open-label (Weeks 12-52) | Lack of Efficacy | 9 | 8 |
| Period II - Open-label (Weeks 12-52) | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo / Sitagliptin | Total | Sitagliptin / Sitagliptin |
|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 9.2 | 58.4 years STANDARD_DEVIATION 9.5 | 57.8 years STANDARD_DEVIATION 9.9 |
| Fasting Plasma Glucose | 151.3 mg/dL STANDARD_DEVIATION 34.6 | 149.1 mg/dL STANDARD_DEVIATION 33.8 | 146.8 mg/dL STANDARD_DEVIATION 33.1 |
| Hemoglobin A1c (HbA1c) | 7.6 Percent STANDARD_DEVIATION 0.8 | 7.7 Percent STANDARD_DEVIATION 0.8 | 7.7 Percent STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 19 Participants | 47 Participants | 28 Participants |
| Sex: Female, Male Male | 49 Participants | 87 Participants | 38 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 | 21 / — | 23 / — | 80 / — |
| serious Total, serious adverse events | 3 / — | 1 / — | 7 / — |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 12
Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
Time frame: 12 Weeks
Population: Analysis in the Full Analysis Set with Last Observation Carried Forward (The Full Analysis Set population includes all randomized patients who took at least 1 dose of study medication and had both a baseline and at least one post-baseline value.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin / Sitagliptin | Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 12 | -0.4 Percent |
| Placebo / Sitagliptin | Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 12 | 0.4 Percent |
p-value: <0.00195% CI: [-1, -0.6]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose at Week 12
Change from baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
Time frame: 12 Weeks
Population: Analysis in the Full Analysis Set with Last Observation Carried Forward (The Full Analysis Set population includes all randomized patients who took at least 1 dose of study medication and had both a baseline and at least one post-baseline value.)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin / Sitagliptin | Change From Baseline in Fasting Plasma Glucose at Week 12 | -12.2 mg/dL |
| Placebo / Sitagliptin | Change From Baseline in Fasting Plasma Glucose at Week 12 | 4.4 mg/dL |
p-value: <0.00195% CI: [-23.4, -10]ANCOVA
Other Pre-specified
Change From Baseline in 2 Hour Postprandial Glucose at Week 12
Change from baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
Time frame: 12 weeks
Population: Analysis in the Full Analysis Set without Last Observation Carried Forward (The Full Analysis Set population includes all randomized patients who took at least 1 dose of study medication and had both a baseline and at least one post-baseline values.).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin / Sitagliptin | Change From Baseline in 2 Hour Postprandial Glucose at Week 12 | -42.7 mg/dL |
| Placebo / Sitagliptin | Change From Baseline in 2 Hour Postprandial Glucose at Week 12 | 6.4 mg/dL |
p-value: <0.00195% CI: [-64.5, -33.9]ANCOVA
Other Pre-specified
Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 52
Change from the last value before receiving sitagliptin therapy: Week 0 for Sitagliptin/Sitagliptin group and Week 12 for the Placebo/Sitagliptin group.
Time frame: Week 52 (reflecting change from Week 0) for Sitagliptin/Sitagliptin group; Weeks 52 (reflecting change from Week 12) for Placebo/Sitagliptin group.
Population: The Completers Population (CP) includes all randomized patients who took at least 1 dose of sitagliptin and had \[1\] a baseline (Sitagliptin/Sitagliptin group) or Week 12 (Placebo/Sitagliptin group) value and \[2\] a value at Week 52.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sitagliptin / Sitagliptin | Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 52 | -0.6 Percent |
| Placebo / Sitagliptin | Change From Baseline in Hemoglobin A1c (HbA1c ) at Week 52 | -0.9 Percent |