Trial Outcomes & Findings for Metformin Add-on Regimen Comparison Study in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431A-136) (NCT NCT01545388)
NCT ID: NCT01545388
Last Updated: 2018-08-22
Results Overview
Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
337 participants
Primary outcome timeframe
Baseline and Week 24
Results posted on
2018-08-22
Participant Flow
Participant milestones
| Measure |
Metformin 500 mg q.d.
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Overall Study
STARTED
|
138
|
133
|
66
|
|
Overall Study
COMPLETED
|
130
|
122
|
58
|
|
Overall Study
NOT COMPLETED
|
8
|
11
|
8
|
Reasons for withdrawal
| Measure |
Metformin 500 mg q.d.
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
4
|
1
|
|
Overall Study
Lack of Efficacy
|
3
|
2
|
5
|
|
Overall Study
Participant moved or relocated
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
4
|
2
|
|
Overall Study
Other
|
1
|
1
|
0
|
Baseline Characteristics
Metformin Add-on Regimen Comparison Study in Japanese Participants With Type 2 Diabetes Mellitus (MK-0431A-136)
Baseline characteristics by cohort
| Measure |
Metformin 500 mg q.d.
n=138 Participants
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
n=133 Participants
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
n=66 Participants
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
Total
n=337 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
59.46 Years
STANDARD_DEVIATION 9.61 • n=5 Participants
|
59.65 Years
STANDARD_DEVIATION 9.22 • n=7 Participants
|
60.05 Years
STANDARD_DEVIATION 9.30 • n=5 Participants
|
59.65 Years
STANDARD_DEVIATION 9.37 • n=4 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
126 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
211 Participants
n=4 Participants
|
|
Hemoglobin A1c (HbA1c)
|
7.60 Percent of glycosylated hemoglobin
STANDARD_DEVIATION 0.83 • n=5 Participants
|
7.40 Percent of glycosylated hemoglobin
STANDARD_DEVIATION 0.68 • n=7 Participants
|
7.53 Percent of glycosylated hemoglobin
STANDARD_DEVIATION 0.77 • n=5 Participants
|
7.51 Percent of glycosylated hemoglobin
STANDARD_DEVIATION 0.76 • n=4 Participants
|
|
Fasting plasma glucose (FPG)
|
158.58 mg/dL
STANDARD_DEVIATION 32.45 • n=5 Participants
|
148.98 mg/dL
STANDARD_DEVIATION 26.27 • n=7 Participants
|
154.27 mg/dL
STANDARD_DEVIATION 27.51 • n=5 Participants
|
153.95 mg/dL
STANDARD_DEVIATION 29.42 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: Per-protocol population defined as all randomized participants who had at least one measurement (baseline or post-randomization), with participants and/or selected data excluded due to protocol violations.
Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.
Outcome measures
| Measure |
Metformin 500 mg q.d.
n=136 Participants
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
n=130 Participants
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
n=66 Participants
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c)
|
-0.434 Percent of glycosylated hemoglobin
Interval -0.553 to -0.315
|
-0.587 Percent of glycosylated hemoglobin
Interval -0.708 to -0.467
|
0.091 Percent of glycosylated hemoglobin
Interval -0.073 to 0.255
|
PRIMARY outcome
Timeframe: Up to 26 weeksPopulation: All participants as treated defined as all randomized participants who received at least one dose of study treatment.
Outcome measures
| Measure |
Metformin 500 mg q.d.
n=138 Participants
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
n=133 Participants
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
n=66 Participants
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Percentage of Participants Who Experienced at Least One Adverse Event
|
65.9 Percentage of participants
|
67.7 Percentage of participants
|
60.6 Percentage of participants
|
PRIMARY outcome
Timeframe: Up to 24 weeksPopulation: All participants as treated defined as all randomized participants who received at least one dose of study treatment.
Outcome measures
| Measure |
Metformin 500 mg q.d.
n=138 Participants
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
n=133 Participants
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
n=66 Participants
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
|
2 Participants
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: Per-protocol population defined as all randomized participants who had at least one measurement (baseline or post-randomization), with participants and/or selected data excluded due to protocol violations.
Based on a cLDA model with terms for treatment, other prior AHA therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.
Outcome measures
| Measure |
Metformin 500 mg q.d.
n=136 Participants
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
n=130 Participants
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
n=66 Participants
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG)
|
-9.02 mg/dL
Interval -13.74 to -4.3
|
-11.27 mg/dL
Interval -16.07 to -6.46
|
7.32 mg/dL
Interval 0.86 to 13.79
|
Adverse Events
Metformin 500 mg q.d.
Serious events: 4 serious events
Other events: 29 other events
Deaths: 0 deaths
Metformin 250 mg b.i.d.
Serious events: 2 serious events
Other events: 35 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Metformin 500 mg q.d.
n=138 participants at risk
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
n=133 participants at risk
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
n=66 participants at risk
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/138 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.75%
1/133 • Number of events 1 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/66 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Gastroenteritis
|
0.72%
1/138 • Number of events 1 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/133 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/66 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Sternal fracture
|
0.72%
1/138 • Number of events 1 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/133 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/66 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Brain stem infarction
|
0.00%
0/138 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.75%
1/133 • Number of events 1 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/66 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
|
Nervous system disorders
Cerebral infarction
|
0.72%
1/138 • Number of events 1 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/133 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/66 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.72%
1/138 • Number of events 1 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/133 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/66 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
Other adverse events
| Measure |
Metformin 500 mg q.d.
n=138 participants at risk
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
|
Metformin 250 mg b.i.d.
n=133 participants at risk
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
|
Placebo
n=66 participants at risk
Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening.
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
5.8%
8/138 • Number of events 8 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
3.8%
5/133 • Number of events 6 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
0.00%
0/66 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
|
Infections and infestations
Nasopharyngitis
|
12.3%
17/138 • Number of events 21 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
21.1%
28/133 • Number of events 31 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
10.6%
7/66 • Number of events 7 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
5.8%
8/138 • Number of events 9 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
3.0%
4/133 • Number of events 5 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
1.5%
1/66 • Number of events 2 • Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
|
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 The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER