Trial Outcomes & Findings for Bioequivalence Study of Sitagliptin/Metformin Combination Tablet (MK0431A-122) (NCT NCT01093794)
NCT ID: NCT01093794
Last Updated: 2015-07-28
Results Overview
AUC (0-t) is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
28 participants
Primary outcome timeframe
baseline through 72 hours postdose
Results posted on
2015-07-28
Participant Flow
28 participants were randomized in four treatment sequences. Participants had a 7 day minimum washout period between treatments.
Participant milestones
| Measure |
1. Sit + Met500 / SitMet500 FDC / SitMet850 FDC / Sit + Met850
Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments:
* Co-administration of 50 mg sitagliptin and 500 mg metformin
* sitagliptin/metformin 50 mg/500 mg FDC tablet
* sitagliptin/metformin 50 mg/850 mg FDC tablet
* Co-administration of 50 mg sitagliptin and 850 mg metformin
|
2. SitMet500 FDC / Sit + Met850 / Sit + Met500 / SitMet850 FDC
Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments:
* sitagliptin/metformin 50 mg/500 mg FDC tablet
* Co-administration of 50 mg sitagliptin and 850 mg metformin
* Co-administration of 50 mg sitagliptin and 500mg metformin
* sitagliptin/metformin 50 mg/850 mg FDC tablet
|
3. Sit + Met850 / SitMet850 FDC / SitMet500 FDC / Sit + Met500
Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments:
* Co-administration of 50 mg sitagliptin and 850 mg metformin
* sitagliptin/metformin 50 mg/850 mg FDC tablet
* sitagliptin/metformin 50 mg/500 mg FDC tablet
* Co-administration of 50 mg sitagliptin and 500mg metformin
|
4. SitMet850 FDC / Sit + Met500 / Sit + Met850 / SitMet500 FDC
Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments:
* sitagliptin/metformin 50 mg/850 mg FDC tablet
* Co-administration of 50 mg sitagliptin and 500 mg metformin
* Co-administration of 50 mg sitagliptin and 850 mg metformin
* sitagliptin/metformin 50 mg/500 mg FDC tablet
|
|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
7
|
7
|
7
|
7
|
|
Treatment Period 1
COMPLETED
|
7
|
7
|
7
|
7
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
7
|
7
|
6
|
7
|
|
Treatment Period 2
COMPLETED
|
7
|
7
|
6
|
7
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Treatment Period 3
STARTED
|
7
|
7
|
6
|
7
|
|
Treatment Period 3
COMPLETED
|
7
|
7
|
6
|
7
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Treatment Period 4
STARTED
|
7
|
7
|
6
|
7
|
|
Treatment Period 4
COMPLETED
|
7
|
7
|
6
|
7
|
|
Treatment Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioequivalence Study of Sitagliptin/Metformin Combination Tablet (MK0431A-122)
Baseline characteristics by cohort
| Measure |
All Participants
n=28 Participants
|
|---|---|
|
Age, Continuous
|
28.6 years
STANDARD_DEVIATION 5.61 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
|
Region of Enrollment
China
|
28 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
22 kg/m^2
STANDARD_DEVIATION 1.22 • n=5 Participants
|
PRIMARY outcome
Timeframe: baseline through 72 hours postdosePopulation: Per-Protocol (PP) set: Participants who completed the study according to the protocol. One participant who discontinued after Treatment Period 1 was not included in the analysis.
AUC (0-t) is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg.
Outcome measures
| Measure |
Sit 50 mg + Met 500 mg
n=27 Participants
Participants co-administered 50 mg sitagliptin and 500 mg metformin as individual tablets from all treatment sequences.
|
SitMet 50mg/500mg FDC
n=27 Participants
Participants administered the sitagliptin/metformin 50 mg/500 mg FDC tablet from all treatment sequences.
|
Sit 50 mg + Met 850 mg
n=27 Participants
Participants co-administered 50 mg sitagliptin and 850mg metformin as individual tablets from all treatment sequences.
|
SitMet 50mg/850mg FDC
n=27 Participants
Participants administered sitagliptin/metformin 50 mg/850 mg FDC tablet from all treatment sequences.
|
|---|---|---|---|---|
|
Area Under the Curve (AUC(0-t)) for Sitagliptin
sitagliptin 50 mg
|
1570 hr*ng/mL
Standard Deviation 217.40
|
1590 hr*ng/mL
Standard Deviation 186.58
|
1520 hr*ng/mL
Standard Deviation 228.83
|
1600 hr*ng/mL
Standard Deviation 195.05
|
|
Area Under the Curve (AUC(0-t)) for Sitagliptin
metformin 500 mg
|
8350 hr*ng/mL
Standard Deviation 1881.70
|
8750 hr*ng/mL
Standard Deviation 1920.45
|
NA hr*ng/mL
Standard Deviation NA
Metformin 500 mg was not administered during this treatment.
|
NA hr*ng/mL
Standard Deviation NA
Metformin 500 mg was not administered during this treatment.
|
|
Area Under the Curve (AUC(0-t)) for Sitagliptin
metformin 850 mg
|
NA hr*ng/mL
Standard Deviation NA
Metformin 850 mg was not administered during this treatment.
|
NA hr*ng/mL
Standard Deviation NA
Metformin 850 mg was not administered during this treatment.
|
11800 hr*ng/mL
Standard Deviation 2849.36
|
13100 hr*ng/mL
Standard Deviation 2987.28
|
PRIMARY outcome
Timeframe: baseline through 72 hours postdosePopulation: Per-Protocol (PP) set: Participants who completed the study according to the protocol. One participant who discontinued after Treatment Period 1 was not included in the analysis.
Cmax is the peak serum concentration of a therapeutic drug after administration; and is used to determine the rate and extent of drug absorption. Cmax is reported for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg.
Outcome measures
| Measure |
Sit 50 mg + Met 500 mg
n=27 Participants
Participants co-administered 50 mg sitagliptin and 500 mg metformin as individual tablets from all treatment sequences.
|
SitMet 50mg/500mg FDC
n=27 Participants
Participants administered the sitagliptin/metformin 50 mg/500 mg FDC tablet from all treatment sequences.
|
Sit 50 mg + Met 850 mg
n=27 Participants
Participants co-administered 50 mg sitagliptin and 850mg metformin as individual tablets from all treatment sequences.
|
SitMet 50mg/850mg FDC
n=27 Participants
Participants administered sitagliptin/metformin 50 mg/850 mg FDC tablet from all treatment sequences.
|
|---|---|---|---|---|
|
Cmax for Sitagliptin and Metformin
sitagliptin 50 mg
|
189 ng/mL
Standard Deviation 37.76
|
182 ng/mL
Standard Deviation 38.71
|
187 ng/mL
Standard Deviation 40.31
|
194 ng/mL
Standard Deviation 32.67
|
|
Cmax for Sitagliptin and Metformin
Metformin 500 mg
|
1210 ng/mL
Standard Deviation 323.83
|
1310 ng/mL
Standard Deviation 383.57
|
NA ng/mL
Standard Deviation NA
Metformin 500 mg was not administered during this treatment.
|
NA ng/mL
Standard Deviation NA
Metformin 500 mg was not administered during this treatment.
|
|
Cmax for Sitagliptin and Metformin
Metformin 850 mg
|
NA ng/mL
Standard Deviation NA
Metformin 850 mg was not administered during this treatment.
|
NA ng/mL
Standard Deviation NA
Metformin 850 mg was not administered during this treatment.
|
1790 ng/mL
Standard Deviation 488.51
|
1970 ng/mL
Standard Deviation 482.69
|
Adverse Events
Sit 50 mg + Met 500 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Sit/Met 50 mg/500 mg FDC
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Sit 50 mg + Met 850 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Sit/Met 50 mg/850 mg FDC
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sit 50 mg + Met 500 mg
n=28 participants at risk
AEs reported in participants after co-administration of 50 mg sitagliptin and 500 mg metformin.
|
Sit/Met 50 mg/500 mg FDC
n=28 participants at risk
AEs reported in participants after administration of the sitagliptin/metformin 50 mg/500 mg fixed dose combination (FDC) tablet.
|
Sit 50 mg + Met 850 mg
n=28 participants at risk
AEs reported in participants after co-administration of 50 mg sitagliptin and 850 mg metformin.
|
Sit/Met 50 mg/850 mg FDC
n=28 participants at risk
AEs reported in participants after administration of sitagliptin 50 mg/metformin 850 mg FDC tablet.
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
3.6%
1/28
|
0.00%
0/28
|
0.00%
0/28
|
0.00%
0/28
|
|
Gastrointestinal disorders
Abdominal pain
|
3.6%
1/28
|
3.6%
1/28
|
3.6%
1/28
|
3.6%
1/28
|
|
Gastrointestinal disorders
Diarrhea
|
7.1%
2/28
|
3.6%
1/28
|
3.6%
1/28
|
0.00%
0/28
|
|
General disorders
Fever
|
3.6%
1/28
|
0.00%
0/28
|
0.00%
0/28
|
0.00%
0/28
|
|
Ear and labyrinth disorders
Vertigo
|
3.6%
1/28
|
0.00%
0/28
|
0.00%
0/28
|
0.00%
0/28
|
|
Gastrointestinal disorders
Nausea
|
3.6%
1/28
|
3.6%
1/28
|
0.00%
0/28
|
0.00%
0/28
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/28
|
0.00%
0/28
|
7.1%
2/28
|
0.00%
0/28
|
|
General disorders
Chest pain
|
0.00%
0/28
|
0.00%
0/28
|
3.6%
1/28
|
0.00%
0/28
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/28
|
0.00%
0/28
|
3.6%
1/28
|
0.00%
0/28
|
|
Blood and lymphatic system disorders
Leucocytosis
|
0.00%
0/28
|
0.00%
0/28
|
0.00%
0/28
|
3.6%
1/28
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
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. SPONSOR review can be expedited to meet publication guidelines.
- Publication restrictions are in place
Restriction type: OTHER