Trial Outcomes & Findings for MK0431A Comparative Study in Patients With Type 2 Diabetes (0431A-079)(COMPLETED) (NCT NCT00482729)

Last Updated: 2017-06-09

Results Overview

A1C is measured as percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1246 participants

Primary outcome timeframe

Baseline and Week 18

Results posted on

2017-06-09

Participant Flow

First Patient In: 26-Jun-2007; Last Patient Last Visit for end of study: 28-Apr-2009; Two-hundred four medical clinics in the United States (US) and 5 in Puerto Rico.

Patients 18-78 years of age with type 2 diabetes mellitus (T2DM) with inadequate glycemic control (hemoglobin A1c \[A1C\] \>7.5% at screening visit) who were appropriate for treatment with oral antihyperglycemic therapy and had not been on an anti-hyperglycemic agent (AHA) in the last 4 months were eligible to participate.

Participant milestones

Participant milestones
Measure	Sita/Met FDC The Sitagliptin/Metformin Fixed Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Overall Study STARTED	626	624
Overall Study Completed Phase A	484	482
Overall Study Completed Phase B	409	406
Overall Study COMPLETED	409	406
Overall Study NOT COMPLETED	217	218

Reasons for withdrawal

Reasons for withdrawal
Measure	Sita/Met FDC The Sitagliptin/Metformin Fixed Dose Combination (Sita/Met FDC) group includes data from patients randomized to receive treatment with oral tablets of Sita/Met 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Overall Study Adverse Event	29	33
Overall Study Creatinine/Creatinine Clearance Criteria	0	2
Overall Study Hyperglycemia Criteria	7	5
Overall Study Lack of Efficacy	4	16
Overall Study Lost to Follow-up	86	66
Overall Study Physician Decision	10	7
Overall Study Pregnancy	4	2
Overall Study Protocol Violation	10	18
Overall Study Withdrawal by Subject	67	69

Baseline Characteristics

MK0431A Comparative Study in Patients With Type 2 Diabetes (0431A-079)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sita/Met FDC n=625 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 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin n=621 Participants The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Total n=1246 Participants Total of all reporting groups
Age, Continuous	49.4 years STANDARD_DEVIATION 10.5 • n=5 Participants	50.0 years STANDARD_DEVIATION 10.5 • n=7 Participants	49.7 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	272 Participants n=5 Participants	266 Participants n=7 Participants	538 Participants n=5 Participants
Sex: Female, Male Male	353 Participants n=5 Participants	355 Participants n=7 Participants	708 Participants n=5 Participants
Race/Ethnicity, Customized Asian	17 Participants n=5 Participants	24 Participants n=7 Participants	41 Participants n=5 Participants
Race/Ethnicity, Customized Black	82 Participants n=5 Participants	88 Participants n=7 Participants	170 Participants n=5 Participants
Race/Ethnicity, Customized White	508 Participants n=5 Participants	489 Participants n=7 Participants	997 Participants n=5 Participants
Race/Ethnicity, Customized Other	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Hemoglobin A1c (A1C)	9.91 Percent STANDARD_DEVIATION 1.83 • n=5 Participants	9.83 Percent STANDARD_DEVIATION 1.77 • n=7 Participants	9.87 Percent STANDARD_DEVIATION 1.80 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 18

Population: The Full Analysis Set (FAS) included all patients who received at least 1 dose of double-blind study therapy, had a baseline value and ≥ 1 post-baseline value for this outcome. Data after initiation of additional AHA were treated as missing. For FAS with no data at Week 18, the last post-baseline observed measurement was carried forward to Week 18.

A1C is measured as percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=559 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 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin n=564 Participants The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Change From Baseline in Hemoglobin A1c (A1C) at Week 18	-2.37 Percent Interval -2.49 to -2.24	-1.76 Percent Interval -1.88 to -1.64

SECONDARY outcome

Timeframe: Week 18

Population: The Full Analysis Set (FAS) included all patients who received at least 1 dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were treated as missing. For FAS with no data at Week 18, the last post-baseline observed measurement was carried forward to Week 18.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=559 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 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin n=564 Participants The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Number of Patients With A1C < 7.0% at Week 18 Patients with A1C <7.0% at Week 18	275 Participants	193 Participants
Number of Patients With A1C < 7.0% at Week 18 Patients with A1C ≥7.0% at Week 18	284 Participants	371 Participants

SECONDARY outcome

Timeframe: Baseline and Week 18

Population: The Full Analysis Set (FAS) included all patients who received at least 1dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were treated as missing. For FAS with no data at Week 18, the last post-baseline observed measurement was carried forward to Week 18.

FPG is measured as mg/dL. Thus, this change from baseline reflects the Week 18 FPG mg/dL minus the Week 0 FPG mg/dL.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=560 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 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin n=566 Participants The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18	-69.4 mg/dL Interval -74.1 to -64.6	-53.7 mg/dL Interval -58.4 to -48.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 44

Population: The Full Analysis Set (FAS) included all patients who received at least 1 dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were included. For FAS with no data at Week 44, the last post-baseline observed measurement was carried forward to Week 44.

A1C is measured as percent. Thus, this change from baseline reflects the Week 44 A1C percent minus the Week 0 A1C percent.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=560 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 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin n=569 Participants The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Change From Baseline in A1C at Week 44	-2.25 Percent Interval -2.38 to -2.12	-1.77 Percent Interval -1.89 to -1.64

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 44

Population: The Full Analysis Set (FAS) included all patients who received at least 1dose of double-blind study therapy, had a baseline value and ≥1 post-baseline value for this outcome. Data after initiation of additional AHA were included. For FAS with no data at Week 44, the last post-baseline observed measurement was carried forward to Week 44.

Outcome measures

Outcome measures
Measure	Sita/Met FDC n=560 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 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin n=569 Participants The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Number of Patients With A1C < 7.0% at Week 44 Patients with A1C <7.0% at Week 44	258 Participants	173 Participants
Number of Patients With A1C < 7.0% at Week 44 Patients with A1C ≥7.0% at Week 44	302 Participants	396 Participants

Adverse Events

Sita/Met FDC

Serious events: 28 serious events

Other events: 173 other events

Deaths: 0 deaths

Metformin

Serious events: 38 serious events

Other events: 185 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sita/Met FDC n=625 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 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.; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.	Metformin n=621 participants at risk The Metformin group includes data from patients randomized to receive treatment with oral tablets of metformin initiated at a dose of 500 mg twice a day (b.i.d.) The dose was to have been up-titrated over 4 weeks to 1000 mg b.i.d. ; however, patients could stay in the study on a minimum dose of Sita/Met 50/500 mg b.i.d. if a higher dose was not tolerated.
Gastrointestinal disorders Any Gastrointestinal Disorders	17.1% 107/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	21.9% 136/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.
Gastrointestinal disorders Diarrhoea	13.8% 86/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	18.0% 112/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.
Gastrointestinal disorders Nausea	5.9% 37/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	7.1% 44/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.
Infections and infestations Any Infections and infestations	9.9% 62/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	9.2% 57/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.
Infections and infestations Nasopharyngitis	5.3% 33/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	4.2% 26/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.
Infections and infestations Upper respiratory tract infection	4.8% 30/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	5.0% 31/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.
Nervous system disorders Any Nervous system disorders	5.6% 35/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	3.7% 23/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.
Nervous system disorders Headache	5.6% 35/625 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.	3.7% 23/621 • Week 0 through Week 44 1 patient in the Sita/Met FDC group and 3 patients in the Metformin group from Site 079011301, which was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from all four randomized patients at this site were deemed unreliable and were excluded from the primary efficacy and safety analysis.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

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