Trial Outcomes & Findings for The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology (NCT NCT01112670)
NCT ID: NCT01112670
Last Updated: 2013-01-24
Results Overview
COMPLETED
PHASE4
33 participants
0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose
2013-01-24
Participant Flow
Healthy volunteers were recruited from the Denver metro area between November 2009 and December 2010.
Participants (n=145) were genetically pre-screened for ABCB1 1236/2677/3435 diplotypes. Those who possessed the needed ABCB1 genetic diplotypes, along with requisite clinical inclusion criteria, were started in the study (n=33).
Participant milestones
| Measure |
ABCB1 Group 1
ABCB1 CGC/CGC genetic make-up. Sitagliptin to Sitagliptin+Atorvastatin. 8 participants started. 7 participants completed.
|
ABCB1 Group 1*
ABCB1 CGC/CGC genetic make-up. Sitagliptin+Atorvastatin to Sitagliptin. 3 participants started. 3 participants completed.
|
ABCB1 Group 2
ABCB1 CGC/TTT genetic make-up. Sitagliptin to Sitagliptin+Atorvastatin. 7 participants started. 6 participants completed.
|
ABCB1 Group 2*
ABCB1 CGC/TTT genetic make-up. Sitagliptin+Atorvastatin to Sitagiptin. 4 participants started. 4 participants completed.
|
ABCB1 Group 3
ABCB1 TTT/TTT genetic make-up. Sitagliptin to Sitagliptin+Atorvastatin. 6 participants started. 5 participants completed.
|
ABCB1 Group 3*
ABCB1 TTT/TTT genetic make-up. Sitagliptin+Atorvastatin to Sitagliptin. 5 participants started. 5 participants completed.
|
|---|---|---|---|---|---|---|
|
Sitagliptin to Sitagliptin+Atorvastatin
STARTED
|
8
|
0
|
7
|
0
|
6
|
0
|
|
Sitagliptin to Sitagliptin+Atorvastatin
COMPLETED
|
7
|
0
|
6
|
0
|
5
|
0
|
|
Sitagliptin to Sitagliptin+Atorvastatin
NOT COMPLETED
|
1
|
0
|
1
|
0
|
1
|
0
|
|
Sitagliptin+Atorvastatin to Sitagliptin
STARTED
|
0
|
3
|
0
|
4
|
0
|
5
|
|
Sitagliptin+Atorvastatin to Sitagliptin
COMPLETED
|
0
|
3
|
0
|
4
|
0
|
5
|
|
Sitagliptin+Atorvastatin to Sitagliptin
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology
Baseline characteristics by cohort
| Measure |
Overall Study Population
n=33 Participants
All participants who participated in at least one period of the study (n=33)
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
33 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
33 years
STANDARD_DEVIATION 10 • n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Sitagliptin Monotherapy: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity
|
3638 ng*hr/ml
Standard Deviation 1439
|
3502 ng*hr/ml
Standard Deviation 1133
|
3129 ng*hr/ml
Standard Deviation 795
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Sitagliptin Monotherapy: Sitagliptin Maximum Plasma Concentration (Cmax)
|
454 ng/ml
Standard Deviation 180
|
438 ng/ml
Standard Deviation 152
|
394 ng/ml
Standard Deviation 160
|
PRIMARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study and who had complete urine data.
Outcome measures
| Measure |
ABCB1 Group 1
n=7 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=9 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Sitagliptin Monotherapy: Sitagliptin Renal Clearance (CLr)
|
254 ml/min
Standard Deviation 176
|
232 ml/min
Standard Deviation 62
|
359 ml/min
Standard Deviation 182
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Sitagliptin + Atorvastatin: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity
|
3501 ng*h/ml
Standard Deviation 1617
|
3430 ng*h/ml
Standard Deviation 1279
|
3117 ng*h/ml
Standard Deviation 1216
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Sitagliptin + Atorvastatin: Sitagliptin Maximum Plasma Concentration (Cmax)
|
428 ng/ml
Standard Deviation 201
|
420 ng/ml
Standard Deviation 137
|
370 ng/ml
Standard Deviation 217
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study and who had complete urine data.
Outcome measures
| Measure |
ABCB1 Group 1
n=7 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=9 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Sitagliptin + Atorvastatin: Sitagliptin Renal Clearance (CLr)
|
280 ml/min
Standard Deviation 124
|
226 ml/min
Standard Deviation 66
|
339 ml/min
Standard Deviation 188
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
AUC of sitagliptin when administered with atorvastatin divided by AUC of sitagliptin when administered alone
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Relative Change in Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity
|
0.96 ratio
Interval 0.81 to 1.11
|
0.98 ratio
Interval 0.88 to 1.07
|
0.97 ratio
Interval 0.87 to 1.08
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
Cmax of sitagliptin when administered with atorvastatin divided by Cmax of sitagliptin when administered alone
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Relative Change in Sitagliptin Maximum Plasma Concentration (Cmax)
|
0.96 ratio
Interval 0.75 to 1.17
|
1.0 ratio
Interval 0.79 to 1.21
|
0.93 ratio
Interval 0.76 to 1.11
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hoursPopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study and who had complete urine data.
CLr of sitagliptin when administered with atorvastatin divided by CLr of sitagliptin when administered alone
Outcome measures
| Measure |
ABCB1 Group 1
n=7 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=9 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Relative Change in Sitagliptin Renal Clearance (CLr)
|
1.22 ratio
Interval 0.97 to 1.48
|
0.99 ratio
Interval 0.82 to 1.16
|
1.0 ratio
Interval 0.81 to 1.18
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Atorvastatin Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (0-24 Hours)
|
44.4 ng*h/ml
Standard Deviation 28.0
|
35.4 ng*h/ml
Standard Deviation 35.6
|
49.0 ng*h/ml
Standard Deviation 37.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dosePopulation: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.
Outcome measures
| Measure |
ABCB1 Group 1
n=9 Participants
ABCB1 CGC/CGC genetic make-up
|
ABCB1 Group 2
n=10 Participants
ABCB1 CGC/TTT genetic make-up
|
ABCB1 Group 3
n=10 Participants
ABCB1 TTT/TTT genetic make-up
|
|---|---|---|---|
|
Atorvastatin Maximum Plasma Concentration (Cmax)
|
8.6 ng/ml
Standard Deviation 6.2
|
7.5 ng/ml
Standard Deviation 7.6
|
10.6 ng/ml
Standard Deviation 7.4
|
Adverse Events
Overall Study Population
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Overall Study Population
n=33 participants at risk
All participants who started the study (n=33)
|
|---|---|
|
General disorders
Headache
|
33.3%
11/33 • Number of events 11 • Pharmacokinetic study periods
|
|
General disorders
Lightheadedness
|
9.1%
3/33 • Number of events 3 • Pharmacokinetic study periods
|
|
Musculoskeletal and connective tissue disorders
Muscle pain
|
6.1%
2/33 • Number of events 2 • Pharmacokinetic study periods
|
|
Gastrointestinal disorders
Nausea
|
6.1%
2/33 • Number of events 2 • Pharmacokinetic study periods
|
|
Gastrointestinal disorders
Diarrhea
|
6.1%
2/33 • Number of events 2 • Pharmacokinetic study periods
|
|
General disorders
Nasal congestion
|
6.1%
2/33 • Number of events 2 • Pharmacokinetic study periods
|
|
Hepatobiliary disorders
Increased liver function tests
|
9.1%
3/33 • Number of events 3 • Pharmacokinetic study periods
|
|
General disorders
Hypoalbuminemia
|
24.2%
8/33 • Number of events 8 • Pharmacokinetic study periods
|
|
General disorders
Pain at IV site
|
9.1%
3/33 • Number of events 3 • Pharmacokinetic study periods
|
|
General disorders
Dry mouth
|
6.1%
2/33 • Number of events 2 • Pharmacokinetic study periods
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place