Type 2 Diabetes Mellitus
Conditions
Brief summary
A 30-week extension to a 24-week study assessing the hemoglobin A1c (HbA1c)- and fasting plasma glucose (FPG)-lowering efficacy of the combination of sitagliptin and pioglitazone in patients with type 2 diabetes mellitus (T2DM) with inadequate glycemic control.
Interventions
DRUGSitagliptin 100 mg q.d.+ Pioglitazone 45 mg q.d.
Patients will receive combination therapy with blinded sitagliptin 100 mg q.d. (q.d. = once daily) and open-label pioglitazone 45 mg q.d. during the up to 30 week extension study. Sitagliptin 100 mg q.d. and pioglitazone 45 mg q.d. will be administered as oral tablets.
DRUGPioglitazone 45 mg q.d. + Sitagliptin 100 mg placebo q.d.
Patients will receive placebo to match sitagliptin 100 mg q.d. (blinded) and open-label pioglitazone 45 mg q.d. during the up to 30 week extension study. The placebo to match sitagliptin 100 mg q.d. (blinded) and open-label pioglitazone 45 mg q.d. will be administered as oral tablets.
DRUGMetformin
Patients not meeting specific glycemic goals during the 30-week extension study will receive open-label metformin at a dose determined by the investigator.
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must complete the double-blind base study (MK-0431-064-00)(NCT00397631) and have at least 75% compliance with study medication during the base study treatment period. * Women of childbearing potential must continue to comply with the protocol-specified contraceptive methods
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Hemoglobin A1c (HbA1c) at Week 54 | Baseline and 54 Weeks | HbA1c is measured as percent. Thus this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Fasting Plasma Glucose (FPG) at Week 54 | Baseline and Week 54 | Change from baseline at Week 54 is defined as Week 54 minus Week 0. |
Participant flow
Recruitment details
First patient in the 30-week extension study: 21-Sep-2007. Last patient last visit of the 30-week extension study: 23-Jan-2009; 53 study centers worldwide.
Pre-assignment details
Patients ≥18 years with type 2 diabetes mellitus (T2DM) and hemoglobin A1c (HbA1c) of 8-12% on diet/exercise meeting all other entry criteria were eligible for participation in the 24-week base study. Patients who completed the base study with \>75% study drug compliance were eligible to enter the 30-week extension study at participating sites.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 100 mg q.d. + Pioglitazone 45 mg q.d. The Sitagliptin 100 mg q.d. + Pioglitazone 45 mg q.d. (q.d. = once daily) group includes extension study data from patients who received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and pioglitazone 45 mg. During the 24-week base study (prior to the entering the extension study), these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and pioglitazone 30 mg. | 164 |
| Pioglitazone 45 mg q.d. The Pioglitazone 45 mg q.d. (q.d. = once daily) group includes extension study data from patients who received once-daily coadministered treatment with oral tablets of placebo to sitagliptin 100 mg and pioglitazone 45 mg. During the 24-week base study (prior to entering the extension study), these patients received once-daily coadministered treatment with oral tablets of placebo to sitagliptin 100 mg and pioglitazone 30 mg. | 153 |
| Total | 317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Needed excluded medication | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Sitagliptin 100 mg q.d. + Pioglitazone 45 mg q.d. | Pioglitazone 45 mg q.d. | Total |
|---|---|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 10 | 52.3 years STANDARD_DEVIATION 11.5 | 51.8 years STANDARD_DEVIATION 10.7 |
| Hemoglobin A1c (HbA1c) | 9.4 Percent STANDARD_DEVIATION 1.2 | 9.4 Percent STANDARD_DEVIATION 1.2 | 9.4 Percent STANDARD_DEVIATION 1.2 |
| Race/Ethnicity, Customized Asian | 42 participants | 41 participants | 83 participants |
| Race/Ethnicity, Customized Black | 7 participants | 3 participants | 10 participants |
| Race/Ethnicity, Customized Other | 22 participants | 24 participants | 46 participants |
| Race/Ethnicity, Customized White | 93 participants | 85 participants | 178 participants |
| Sex: Female, Male Female | 78 Participants | 63 Participants | 141 Participants |
| Sex: Female, Male Male | 86 Participants | 90 Participants | 176 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 164 | 8 / 153 |
| serious Total, serious adverse events | 5 / 164 | 3 / 153 |
Outcome results
Primary
Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Hemoglobin A1c (HbA1c) at Week 54
HbA1c is measured as percent. Thus this change from baseline reflects the Week 54 HbA1c percent minus the Week 0 HbA1c percent.
Time frame: Baseline and 54 Weeks
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 value for this outcome during the 30-week extension study. For FAS patients with no data at Week 54, the last observed measurement during the 30-week extension study was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. + Pioglitazone 45 mg q.d. | Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Hemoglobin A1c (HbA1c) at Week 54 | -2.37 Percent HbA1c |
| Pioglitazone 45 mg q.d. | Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Hemoglobin A1c (HbA1c) at Week 54 | -1.86 Percent HbA1c |
95% CI: [-0.76, -0.26]
Secondary
Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Fasting Plasma Glucose (FPG) at Week 54
Change from baseline at Week 54 is defined as Week 54 minus Week 0.
Time frame: Baseline and Week 54
Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 value for this outcome during the extension study. For FAS patients with no data at Week 54, the last observed measurement during extension study was carried forward to Week 54.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 100 mg q.d. + Pioglitazone 45 mg q.d. | Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Fasting Plasma Glucose (FPG) at Week 54 | -61.3 mg/dL |
| Pioglitazone 45 mg q.d. | Change From Baseline (i.e., Week 0 of the 24-week Base Study) in Fasting Plasma Glucose (FPG) at Week 54 | -52.8 mg/dL |
95% CI: [-16.3, -0.7]