Trial Outcomes & Findings for A Study Comparing the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-142) (NCT NCT01582308)
NCT ID: NCT01582308
Last Updated: 2017-05-30
Results Overview
Percent inhibition of DPP-4 activity at 24 hours after the Day 5 morning dose (i.e., at trough) was determined by analysis of blood samples collected from the study participants.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
24 hours following the final morning dose on Day 5
Results posted on
2017-05-30
Participant Flow
Each treatment sequence started with 2 participants in Period 1. In addition, there were 2 replacement participants; in treatment sequence 5, a participant who discontinued after period 1 (placebo treatment) was replaced and in treatment sequence 7, a participant who discontinued during period 1 (saxagliptin treatment) was replaced.
A washout period of at least 10 days occurred between each treatment period.
Participant milestones
| Measure |
Treatment Sequence 1
Sitagliptin 100 mg in Period 1 followed by saxagliptin 5 mg in Period 2 followed by vildagliptin 50 mg BID in Period 3 followed by placebo in Period 4 followed by vildagliptin 50 mg in Period 5
|
Treatment Sequence 2
Saxagliptin 5 mg in Period 1 followed by vildagliptin 50 mg in Period 2 followed by placebo in Period 3 followed by sitagliptin 100 mg in Period 4 followed by vildagliptin 50 mg BID in Period 5
|
Treatment Sequence 3
Vildagliptin 50 mg in Period 1 followed by vildagliptin 50 mg BID in Period 2 followed by sitagliptin 100 mg in Period 3 followed by saxagliptin 5 mg in Period 4 followed by placebo in Period 5
|
Treatment Sequence 4
Vildagliptin 50 mg BID in Period 1 followed by placebo in Period 2 followed by saxagliptin 5 mg in Period 3 followed by vildagliptin 50 mg in Period 4 followed by sitagliptin 100 mg in Period 5
|
Treatment Sequence 5
Placebo in Period 1 followed by sitagliptin 100 mg in Period 2 followed by vildagliptin 50 mg in Period 3 followed by vildagliptin 50 mg BID in Period 4 followed by saxagliptin 5 mg in Period 5
|
Treatment Sequence 6
Sitagliptin 100 mg in Period 1 followed by vildagliptin 50 mg in Period 2 followed by saxagliptin 5 mg in Period 3 followed by placebo in Period 4 followed by vildagliptin 50 mg BID in Period 5
|
Treatment Sequence 7
Saxagliptin 5 mg in Period 1 followed by vildagliptin 50 mg BID in Period 2 followed by vildagliptin 50 mg in Period 3 followed by sitagliptin 100 mg in Period 4 followed by placebo in Period 5
|
Treatment Sequence 8
Vildagliptin 50 mg in Period 1 followed by placebo in Period 2 followed by vildagliptin 50 mg BID in Period 3 followed by saxagliptin 5 mg in Period 4 followed by sitagliptin 100 mg in Period 5
|
Treatment Sequence 9
Vildagliptin 50 mg BID in Period 1 followed by sitagliptin 100 mg in Period 2 followed by placebo in Period 3 followed by vildagliptin 50 mg in Period 4 followed by saxagliptin 5 mg in Period 5
|
Treatment Sequence 10
Placebo in Period 1 followed by saxagliptin 5 mg in Period 2 followed by sitagliptin 100 mg in Period 3 followed by vildagliptin 50 mg BID in Period 4 followed by vildagliptin 50 mg in Period 5
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
2
|
2
|
2
|
2
|
3
|
2
|
3
|
2
|
2
|
2
|
|
Period 1
COMPLETED
|
2
|
2
|
2
|
2
|
3
|
2
|
2
|
2
|
2
|
2
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
10-day Washout Following Period 1
STARTED
|
2
|
2
|
2
|
2
|
3
|
2
|
2
|
2
|
2
|
2
|
|
10-day Washout Following Period 1
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
10-day Washout Following Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Period 2
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
10-day Washout Following Period 2
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
10-day Washout Following Period 2
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
10-day Washout Following Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Period 3
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
10-day Washout Following Period 3
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
10-day Washout Following Period 3
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
10-day Washout Following Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
2
|
|
Period 4
COMPLETED
|
1
|
2
|
2
|
2
|
2
|
1
|
2
|
2
|
2
|
1
|
|
Period 4
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
1
|
|
10-day Washout Following Period 4
STARTED
|
1
|
2
|
2
|
2
|
2
|
1
|
2
|
2
|
2
|
1
|
|
10-day Washout Following Period 4
COMPLETED
|
1
|
2
|
2
|
2
|
2
|
1
|
2
|
2
|
2
|
1
|
|
10-day Washout Following Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 5
STARTED
|
1
|
2
|
2
|
2
|
2
|
1
|
2
|
2
|
2
|
1
|
|
Period 5
COMPLETED
|
1
|
2
|
2
|
2
|
2
|
1
|
2
|
2
|
2
|
1
|
|
Period 5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence 1
Sitagliptin 100 mg in Period 1 followed by saxagliptin 5 mg in Period 2 followed by vildagliptin 50 mg BID in Period 3 followed by placebo in Period 4 followed by vildagliptin 50 mg in Period 5
|
Treatment Sequence 2
Saxagliptin 5 mg in Period 1 followed by vildagliptin 50 mg in Period 2 followed by placebo in Period 3 followed by sitagliptin 100 mg in Period 4 followed by vildagliptin 50 mg BID in Period 5
|
Treatment Sequence 3
Vildagliptin 50 mg in Period 1 followed by vildagliptin 50 mg BID in Period 2 followed by sitagliptin 100 mg in Period 3 followed by saxagliptin 5 mg in Period 4 followed by placebo in Period 5
|
Treatment Sequence 4
Vildagliptin 50 mg BID in Period 1 followed by placebo in Period 2 followed by saxagliptin 5 mg in Period 3 followed by vildagliptin 50 mg in Period 4 followed by sitagliptin 100 mg in Period 5
|
Treatment Sequence 5
Placebo in Period 1 followed by sitagliptin 100 mg in Period 2 followed by vildagliptin 50 mg in Period 3 followed by vildagliptin 50 mg BID in Period 4 followed by saxagliptin 5 mg in Period 5
|
Treatment Sequence 6
Sitagliptin 100 mg in Period 1 followed by vildagliptin 50 mg in Period 2 followed by saxagliptin 5 mg in Period 3 followed by placebo in Period 4 followed by vildagliptin 50 mg BID in Period 5
|
Treatment Sequence 7
Saxagliptin 5 mg in Period 1 followed by vildagliptin 50 mg BID in Period 2 followed by vildagliptin 50 mg in Period 3 followed by sitagliptin 100 mg in Period 4 followed by placebo in Period 5
|
Treatment Sequence 8
Vildagliptin 50 mg in Period 1 followed by placebo in Period 2 followed by vildagliptin 50 mg BID in Period 3 followed by saxagliptin 5 mg in Period 4 followed by sitagliptin 100 mg in Period 5
|
Treatment Sequence 9
Vildagliptin 50 mg BID in Period 1 followed by sitagliptin 100 mg in Period 2 followed by placebo in Period 3 followed by vildagliptin 50 mg in Period 4 followed by saxagliptin 5 mg in Period 5
|
Treatment Sequence 10
Placebo in Period 1 followed by saxagliptin 5 mg in Period 2 followed by sitagliptin 100 mg in Period 3 followed by vildagliptin 50 mg BID in Period 4 followed by vildagliptin 50 mg in Period 5
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
10-day Washout Following Period 1
Physician Decision
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Period 4
Physician Decision
|
1
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study Comparing the Pharmacokinetic and Pharmacodynamic Profiles for Sitagliptin, Saxagliptin and Vildagliptin in Participants With Type 2 Diabetes Mellitus (T2DM) (MK-0431-142)
Baseline characteristics by cohort
| Measure |
All Enrolled Participants
n=22 Participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 24 hours following the final morning dose on Day 5Population: All participants who had at least at least one measurement.
Percent inhibition of DPP-4 activity at 24 hours after the Day 5 morning dose (i.e., at trough) was determined by analysis of blood samples collected from the study participants.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=17 Participants
Sitagliptin 100 mg daily for 5 days
|
Saxagliptin 5 mg
n=20 Participants
Saxagliptin 5 mg daily for 5 days
|
Vildagliptin 50 mg
n=18 Participants
Vildagliptin 50 mg daily for 5 days
|
Vildagliptin 50 mg BID
n=17 Participants
Vildagliptin 50 mg twice daily for 5 days
|
Placebo
n=17 Participants
Placebo to sitagliptin daily for 5 days
|
|---|---|---|---|---|---|
|
Percent Inhibition of Dipeptidyl Peptidase IV (DPP-4) Activity at Trough
|
91.73 Percent inhibition
Interval 91.37 to 92.08
|
73.50 Percent inhibition
Interval 66.56 to 79.0
|
28.88 Percent inhibition
Interval 17.9 to 38.38
|
90.63 Percent inhibition
Interval 88.93 to 92.06
|
3.49 Percent inhibition
Interval -0.66 to 7.48
|
SECONDARY outcome
Timeframe: Predose (0 Hours) and 0.5, 1, 2, 4, 8, 12, 13 (vildagliptin 50 mg BID only), 14 (vildagliptin 50 mg BID only), 16, 20 and 24 hours after the morning dose on Day 5Population: All participants who had at least at least one measurement.
AUC 0-24hr is the area under the plasma drug concentration-time curve calculated for the 24 hour interval after the Day 5 morning dose.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=20 Participants
Sitagliptin 100 mg daily for 5 days
|
Saxagliptin 5 mg
n=20 Participants
Saxagliptin 5 mg daily for 5 days
|
Vildagliptin 50 mg
n=18 Participants
Vildagliptin 50 mg daily for 5 days
|
Vildagliptin 50 mg BID
n=18 Participants
Vildagliptin 50 mg twice daily for 5 days
|
Placebo
Placebo to sitagliptin daily for 5 days
|
|---|---|---|---|---|---|
|
Pharmacokinetic Analysis: Area Under the Curve 0-24 Hours (AUC 0-24hr)
|
7070 nM*hr
Geometric Coefficient of Variation 25.1
|
370 nM*hr
Geometric Coefficient of Variation 25
|
3100 nM*hr
Geometric Coefficient of Variation 27
|
6600 nM*hr
Geometric Coefficient of Variation 26.3
|
—
|
SECONDARY outcome
Timeframe: Predose (0 hours) and 0.5, 1, 2, 4, 8 and 12 hours after the morning dose on Day 5Population: All participants who had at least at least one measurement. This outcome measure is for the vildagliptin 50 mg BID dose only; therefore, results are only presented for vildagliptin 50 mg BID dose.
AUC 0-12hr is the area under the plasma drug concentration-time curve calculated for the 12 hour interval after the Day 5 morning dose for the vildagliptin 50 mg BID dose only.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=17 Participants
Sitagliptin 100 mg daily for 5 days
|
Saxagliptin 5 mg
Saxagliptin 5 mg daily for 5 days
|
Vildagliptin 50 mg
Vildagliptin 50 mg daily for 5 days
|
Vildagliptin 50 mg BID
Vildagliptin 50 mg twice daily for 5 days
|
Placebo
Placebo to sitagliptin daily for 5 days
|
|---|---|---|---|---|---|
|
Pharmacokinetic Analysis: Area Under the Curve 0-12 Hours (AUC 0-12hr) for Vildagliptin 50 mg BID
|
3720 nM*hr
Geometric Coefficient of Variation 28.9
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose (0 hours) and 0.5, 1, 2, 4, 8, 12, 13 (vildagliptin 50 mg BID only), 14 (vildagliptin 50 mg BID only), 16, 20, 24, 36, 48 and 96 hours after the morning dose on Day 5Population: All participants who had at least at least one measurement.
Measurement of the peak plasma drug concentration following the Day 5 morning dose.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=20 Participants
Sitagliptin 100 mg daily for 5 days
|
Saxagliptin 5 mg
n=20 Participants
Saxagliptin 5 mg daily for 5 days
|
Vildagliptin 50 mg
n=18 Participants
Vildagliptin 50 mg daily for 5 days
|
Vildagliptin 50 mg BID
n=18 Participants
Vildagliptin 50 mg twice daily for 5 days
|
Placebo
Placebo to sitagliptin daily for 5 days
|
|---|---|---|---|---|---|
|
Pharmacokinetic Analysis: Peak Plasma Drug Concentration (Cmax)
|
724 nM
Geometric Coefficient of Variation 31.3
|
88.8 nM
Geometric Coefficient of Variation 25.2
|
586 nM
Geometric Coefficient of Variation 37
|
759 nM
Geometric Coefficient of Variation 34.7
|
—
|
SECONDARY outcome
Timeframe: Predose (0 hours) and 0.5, 1, 2, 4, 8, 12, 13 (vildagliptin 50 mg BID only), 14 (vildagliptin 50 mg BID only), 16, 20, 24, 36, 48 and 96 hours after the morning dose on Day 5Population: All participants who had at least at least one measurement.
Measurement of the time to the peak plasma drug concentration following the Day 5 morning dose.
Outcome measures
| Measure |
Sitagliptin 100 mg
n=20 Participants
Sitagliptin 100 mg daily for 5 days
|
Saxagliptin 5 mg
n=20 Participants
Saxagliptin 5 mg daily for 5 days
|
Vildagliptin 50 mg
n=18 Participants
Vildagliptin 50 mg daily for 5 days
|
Vildagliptin 50 mg BID
n=18 Participants
Vildagliptin 50 mg twice daily for 5 days
|
Placebo
Placebo to sitagliptin daily for 5 days
|
|---|---|---|---|---|---|
|
Pharmacokinetic Analysis: Time to the Peak Plasma Drug Concentration (Tmax)
|
4 hr
Interval 0.5 to 8.0
|
1 hr
Interval 0.5 to 2.0
|
1 hr
Interval 0.5 to 8.0
|
1 hr
Interval 0.5 to 4.0
|
—
|
Adverse Events
Sitagliptin 100 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Saxagliptin 5 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Vildagliptin 50 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Vildagliptin 50 mg BID
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Sitagliptin 100 mg
n=20 participants at risk
Sitagliptin 100 mg daily for 5 days
|
Saxagliptin 5 mg
n=21 participants at risk
Saxagliptin 5 mg daily for 5 days
|
Vildagliptin 50 mg
n=18 participants at risk
Vildagliptin 50 mg daily for 5 days
|
Vildagliptin 50 mg BID
n=19 participants at risk
Vildagliptin 50 mg twice daily for 5 days
|
Placebo
n=21 participants at risk
Placebo to sitagliptin daily for 5 days
|
|---|---|---|---|---|---|
|
Infections and infestations
Influenza
|
0.00%
0/20 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
9.5%
2/21 • Number of events 2 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
0.00%
0/18 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
0.00%
0/19 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
0.00%
0/21 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 2 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
9.5%
2/21 • Number of events 2 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
5.6%
1/18 • Number of events 1 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
5.3%
1/19 • Number of events 1 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
0.00%
0/21 • Through approximately 14 days following the last dose of study drug in Period 5
Of the 22 participants, 5 participants discontinued therapy and did not complete all 5 periods of the study.
|
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