Trial Outcomes & Findings for MK0431A vs. Pioglitazone in Patients With Type 2 Diabetes Mellitus (0431A-066) (NCT NCT00532935)
NCT ID: NCT00532935
Last Updated: 2017-06-09
Results Overview
A1C is measured as a percent. Thus this change from baseline reflects the Week 32 A1C percent minus the baseline A1C percent
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
517 participants
Primary outcome timeframe
Baseline and Week 32
Results posted on
2017-06-09
Participant Flow
First Patient In: 19-Mar-2008 Last Patient Last Visit: 23-Oct-2009 Seventy-four medical clinics worldwide (19 sites in the United States, 31 in Eastern Europe, and 24 in the rest of the world).
Patients 18-78 years old with Type 2 Diabetes Mellitus (T2DM), drug-naïve (off antihyperglycemic agent \[AHA\] for at least 3 months prior to screening, and a maximum 4 weeks cumulative AHA therapy over the previous 3 years), hemoglobin A1C 7.5 to 12% were eligible. Eligible patients underwent a 2-week placebo run-in period prior to randomization.
Participant milestones
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Overall Study
STARTED
|
261
|
256
|
|
Overall Study
COMPLETED
|
210
|
204
|
|
Overall Study
NOT COMPLETED
|
51
|
52
|
Reasons for withdrawal
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Overall Study
Adverse Event
|
11
|
12
|
|
Overall Study
Lack of Efficacy
|
0
|
3
|
|
Overall Study
Lost to Follow-up
|
10
|
6
|
|
Overall Study
Physician Decision
|
4
|
5
|
|
Overall Study
Pregnancy
|
1
|
0
|
|
Overall Study
Protocol Violation
|
4
|
2
|
|
Overall Study
Withdrawal by Subject
|
10
|
9
|
|
Overall Study
Protocol Specific Criteria
|
11
|
15
|
Baseline Characteristics
MK0431A vs. Pioglitazone in Patients With Type 2 Diabetes Mellitus (0431A-066)
Baseline characteristics by cohort
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=261 Participants
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=256 Participants
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Total
n=517 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.4 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
52.2 years
STANDARD_DEVIATION 11 • n=7 Participants
|
52.3 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
118 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
240 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
143 Participants
n=5 Participants
|
134 Participants
n=7 Participants
|
277 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
168 participants
n=5 Participants
|
167 participants
n=7 Participants
|
335 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
58 participants
n=5 Participants
|
55 participants
n=7 Participants
|
113 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multi-racial
|
27 participants
n=5 Participants
|
29 participants
n=7 Participants
|
56 participants
n=5 Participants
|
|
Hemoglobin A1C (A1C)
|
9.0 Percent of glycosylated hemoglobin (A1C)
STANDARD_DEVIATION 1.3 • n=5 Participants
|
8.9 Percent of glycosylated hemoglobin (A1C)
STANDARD_DEVIATION 1.3 • n=7 Participants
|
8.9 Percent of glycosylated hemoglobin (A1C)
STANDARD_DEVIATION 1.3 • n=5 Participants
|
|
Fasting Plasma Glucose (FPG)
|
190.6 mg/dL
STANDARD_DEVIATION 53.4 • n=5 Participants
|
188.9 mg/dL
STANDARD_DEVIATION 57.1 • n=7 Participants
|
189.8 mg/dL
STANDARD_DEVIATION 55.2 • n=5 Participants
|
|
2-Hour Post-Meal Glucose (2-HR PMG)
|
273.7 mg/dL
STANDARD_DEVIATION 84.8 • n=5 Participants
|
278.8 mg/dL
STANDARD_DEVIATION 86.4 • n=7 Participants
|
276.2 mg/dL
STANDARD_DEVIATION 85.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 32Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
A1C is measured as a percent. Thus this change from baseline reflects the Week 32 A1C percent minus the baseline A1C percent
Outcome measures
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=253 Participants
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=246 Participants
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Change From Baseline in A1C at Week 32
|
-1.86 Percent of glycosylated hemoglobin (A1C)
Interval -2.0 to -1.73
|
-1.39 Percent of glycosylated hemoglobin (A1C)
Interval -1.53 to -1.26
|
SECONDARY outcome
Timeframe: Baseline and Week 1Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome.
Change from baseline reflects the Week 1 FPG minus the baseline FPG. At Week 1, the dose was 50/500 mg b.i.d. for Sita/Met FDC and 30 mg q.d. for pioglitazone
Outcome measures
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=250 Participants
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=242 Participants
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 1
|
-40.5 mg/dL
Interval -44.1 to -36.9
|
-13.0 mg/dL
Interval -16.6 to -9.3
|
SECONDARY outcome
Timeframe: Baseline and Week 32Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
Change from baseline reflects the Week 32 2-hour PMG minus the baseline 2-hour PMG
Outcome measures
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=192 Participants
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=198 Participants
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Change From Baseline in 2-hour Post-Meal Glucose (PMG) at Week 32
|
-102.2 mg/dL
Interval -110.7 to -93.8
|
-82.0 mg/dL
Interval -90.4 to -73.7
|
SECONDARY outcome
Timeframe: Baseline and Week 32Population: Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
Change from baseline reflects the Week 32 FPG minus the baseline FPG
Outcome measures
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=258 Participants
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=250 Participants
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Change From Baseline in FPG at Week 32
|
-56.0 mg/dL
Interval -60.9 to -51.0
|
-44.0 mg/dL
Interval -49.1 to -39.0
|
SECONDARY outcome
Timeframe: Week 32Population: The Full Analysis Set (FAS) included all patients who received at least one dose of double-blind study drug and had both a baseline value and ≥ 1 post-baseline value for this outcome. For FAS patients with no data at Week 32, the last non-baseline observed measurement was carried forward to Week 32.
Outcome measures
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=253 Participants
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=246 Participants
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Percent of Participants With A1C <7.0% at Week 32
|
57.3 Percent Participants
|
43.5 Percent Participants
|
Adverse Events
Sitagliptin/Metformin Fixed-Dose Combination
Serious events: 11 serious events
Other events: 94 other events
Deaths: 0 deaths
Pioglitazone
Serious events: 8 serious events
Other events: 68 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=261 participants at risk
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=256 participants at risk
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Eye disorders
Conjunctivitis allergic
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Eye disorders
Ulcerative keratitis
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Gastrointestinal disorders
Pancreatitis
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
|
Hepatobiliary disorders
Cholecystitis
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.1%
3/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Hepatobiliary disorders
Hepatitis
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
|
Infections and infestations
Pneumonia
|
0.00%
0/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Nervous system disorders
Brain stem infarction
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Nervous system disorders
Transient ischaemic attack
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous complete
|
0.38%
1/261 • Week 0 through Week 32
|
0.00%
0/256 • Week 0 through Week 32
|
|
Renal and urinary disorders
Urine flow decreased
|
0.00%
0/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.38%
1/261 • Week 0 through Week 32
|
0.39%
1/256 • Week 0 through Week 32
|
Other adverse events
| Measure |
Sitagliptin/Metformin Fixed-Dose Combination
n=261 participants at risk
The Sitagliptin/Metformin Fixed-Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met FDC initiated at a dose of 50/500 mg twice a day (b.i.d). The dose was to have been up-titrated over 4 weeks to 50/1000 mg b.i.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
Pioglitazone
n=256 participants at risk
The Pioglitazone group includes data from patients randomized to receive treatment with oral tablets of pioglitazone initiated at a dose of 30 mg once daily (q.d.). The dose was to have been up-titrated over 4 weeks to 45 mg q.d. Patients were discontinued if they were considered clinically inappropriate for up-titration or could not be up-titrated or maintained on the up-titrated dose.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
15.3%
40/261 • Week 0 through Week 32
|
4.3%
11/256 • Week 0 through Week 32
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
13/261 • Week 0 through Week 32
|
0.78%
2/256 • Week 0 through Week 32
|
|
General disorders
Oedema peripheral
|
1.1%
3/261 • Week 0 through Week 32
|
7.0%
18/256 • Week 0 through Week 32
|
|
Infections and infestations
Nasopharyngitis
|
3.8%
10/261 • Week 0 through Week 32
|
6.2%
16/256 • Week 0 through Week 32
|
|
Infections and infestations
Upper respiratory tract infection
|
5.0%
13/261 • Week 0 through Week 32
|
6.6%
17/256 • Week 0 through Week 32
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
8.4%
22/261 • Week 0 through Week 32
|
4.3%
11/256 • Week 0 through Week 32
|
|
Nervous system disorders
Headache
|
7.7%
20/261 • Week 0 through Week 32
|
2.7%
7/256 • Week 0 through Week 32
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER