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The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology

The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01112670
Enrollment
33
Registered
2010-04-28
Start date
2009-11-30
Completion date
2011-07-31
Last updated
2013-01-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Healthy volunteers

Brief summary

The purpose of this study is to determine the pharmacogenetics, pharmacokinetics, and drug-drug interactions of sitagliptin therapy.

Interventions

DRUGSitagliptin

sitagliptin 100 mg x 1 dose

DRUGatorvastatin

atorvastatin 40 mg x 5 doses

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
CollaboratorNIH
University of Colorado, Denver
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
Yes

Inclusion criteria

* Healthy men and women between 21 to 60 years of age will be recruited to participate in this study. * Subjects will be eligible if metabolic, renal, hepatic, and hematological laboratory tests are within normal limits.

Exclusion criteria

* Subjects will be excluded from the study if they have a current or past history of cardiovascular, hepatic, endocrine (e.g., diabetes), renal, pancreatic, gastrointestinal, pulmonary, immunologic, hematologic, or neurologic disease.

Design outcomes

Primary

MeasureTime frame
Sitagliptin Monotherapy: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose
Sitagliptin Monotherapy: Sitagliptin Renal Clearance (CLr)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose
Sitagliptin Monotherapy: Sitagliptin Maximum Plasma Concentration (Cmax)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Secondary

MeasureTime frame
Sitagliptin + Atorvastatin: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose
Sitagliptin + Atorvastatin: Sitagliptin Maximum Plasma Concentration (Cmax)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose
Sitagliptin + Atorvastatin: Sitagliptin Renal Clearance (CLr)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Other

MeasureTime frameDescription
Relative Change in Sitagliptin Renal Clearance (CLr)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hoursCLr of sitagliptin when administered with atorvastatin divided by CLr of sitagliptin when administered alone
Relative Change in Sitagliptin Maximum Plasma Concentration (Cmax)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-doseCmax of sitagliptin when administered with atorvastatin divided by Cmax of sitagliptin when administered alone
Atorvastatin Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (0-24 Hours)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose—
Atorvastatin Maximum Plasma Concentration (Cmax)0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose—
Relative Change in Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-doseAUC of sitagliptin when administered with atorvastatin divided by AUC of sitagliptin when administered alone

Countries

United States

Participant flow

Recruitment details

Healthy volunteers were recruited from the Denver metro area between November 2009 and December 2010.

Pre-assignment details

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).

Participants by arm

ArmCount
Overall Study Population
All participants who participated in at least one period of the study (n=33)
33
Total33

Baseline characteristics

CharacteristicOverall Study Population
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
33 Participants
Age Continuous33 years
STANDARD_DEVIATION 10
Sex: Female, Male
Female
16 Participants
Sex: Female, Male
Male
17 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
24 / 33
serious
Total, serious adverse events
0 / 33

Outcome results

Primary

Sitagliptin Monotherapy: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Sitagliptin Monotherapy: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity3638 ng*hr/mlStandard Deviation 1439
ABCB1 Group 2Sitagliptin Monotherapy: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity3502 ng*hr/mlStandard Deviation 1133
ABCB1 Group 3Sitagliptin Monotherapy: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity3129 ng*hr/mlStandard Deviation 795
p-value: 0.83ANOVA
Primary

Sitagliptin Monotherapy: Sitagliptin Maximum Plasma Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Sitagliptin Monotherapy: Sitagliptin Maximum Plasma Concentration (Cmax)454 ng/mlStandard Deviation 180
ABCB1 Group 2Sitagliptin Monotherapy: Sitagliptin Maximum Plasma Concentration (Cmax)438 ng/mlStandard Deviation 152
ABCB1 Group 3Sitagliptin Monotherapy: Sitagliptin Maximum Plasma Concentration (Cmax)394 ng/mlStandard Deviation 160
p-value: 0.67ANOVA
Primary

Sitagliptin Monotherapy: Sitagliptin Renal Clearance (CLr)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study and who had complete urine data.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Sitagliptin Monotherapy: Sitagliptin Renal Clearance (CLr)254 ml/minStandard Deviation 176
ABCB1 Group 2Sitagliptin Monotherapy: Sitagliptin Renal Clearance (CLr)232 ml/minStandard Deviation 62
ABCB1 Group 3Sitagliptin Monotherapy: Sitagliptin Renal Clearance (CLr)359 ml/minStandard Deviation 182
p-value: 0.21ANOVA
Secondary

Sitagliptin + Atorvastatin: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Sitagliptin + Atorvastatin: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity3501 ng*h/mlStandard Deviation 1617
ABCB1 Group 2Sitagliptin + Atorvastatin: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity3430 ng*h/mlStandard Deviation 1279
ABCB1 Group 3Sitagliptin + Atorvastatin: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity3117 ng*h/mlStandard Deviation 1216
p-value: 0.9ANOVA
Secondary

Sitagliptin + Atorvastatin: Sitagliptin Maximum Plasma Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Sitagliptin + Atorvastatin: Sitagliptin Maximum Plasma Concentration (Cmax)428 ng/mlStandard Deviation 201
ABCB1 Group 2Sitagliptin + Atorvastatin: Sitagliptin Maximum Plasma Concentration (Cmax)420 ng/mlStandard Deviation 137
ABCB1 Group 3Sitagliptin + Atorvastatin: Sitagliptin Maximum Plasma Concentration (Cmax)370 ng/mlStandard Deviation 217
p-value: 0.56ANOVA
Secondary

Sitagliptin + Atorvastatin: Sitagliptin Renal Clearance (CLr)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study and who had complete urine data.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Sitagliptin + Atorvastatin: Sitagliptin Renal Clearance (CLr)280 ml/minStandard Deviation 124
ABCB1 Group 2Sitagliptin + Atorvastatin: Sitagliptin Renal Clearance (CLr)226 ml/minStandard Deviation 66
ABCB1 Group 3Sitagliptin + Atorvastatin: Sitagliptin Renal Clearance (CLr)339 ml/minStandard Deviation 188
p-value: 0.22ANOVA
Other Pre-specified

Atorvastatin Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (0-24 Hours)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Atorvastatin Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (0-24 Hours)44.4 ng*h/mlStandard Deviation 28
ABCB1 Group 2Atorvastatin Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (0-24 Hours)35.4 ng*h/mlStandard Deviation 35.6
ABCB1 Group 3Atorvastatin Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (0-24 Hours)49.0 ng*h/mlStandard Deviation 37.1
p-value: 0.29ANOVA
Other Pre-specified

Atorvastatin Maximum Plasma Concentration (Cmax)

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)Dispersion
ABCB1 Group 1Atorvastatin Maximum Plasma Concentration (Cmax)8.6 ng/mlStandard Deviation 6.2
ABCB1 Group 2Atorvastatin Maximum Plasma Concentration (Cmax)7.5 ng/mlStandard Deviation 7.6
ABCB1 Group 3Atorvastatin Maximum Plasma Concentration (Cmax)10.6 ng/mlStandard Deviation 7.4
p-value: 0.43ANOVA
Other Pre-specified

Relative Change in Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity

AUC of sitagliptin when administered with atorvastatin divided by AUC of sitagliptin when administered alone

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)
ABCB1 Group 1Relative Change in Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity0.96 ratio
ABCB1 Group 2Relative Change in Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity0.98 ratio
ABCB1 Group 3Relative Change in Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity0.97 ratio
p-value: 0.97ANOVA
Other Pre-specified

Relative Change in Sitagliptin Maximum Plasma Concentration (Cmax)

Cmax of sitagliptin when administered with atorvastatin divided by Cmax of sitagliptin when administered alone

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study.

ArmMeasureValue (MEAN)
ABCB1 Group 1Relative Change in Sitagliptin Maximum Plasma Concentration (Cmax)0.96 ratio
ABCB1 Group 2Relative Change in Sitagliptin Maximum Plasma Concentration (Cmax)1.0 ratio
ABCB1 Group 3Relative Change in Sitagliptin Maximum Plasma Concentration (Cmax)0.93 ratio
p-value: 0.86ANOVA
Other Pre-specified

Relative Change in Sitagliptin Renal Clearance (CLr)

CLr of sitagliptin when administered with atorvastatin divided by CLr of sitagliptin when administered alone

Time frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours

Population: The population analyzed included participants who completed both periods of the pharmacokinetic crossover study and who had complete urine data.

ArmMeasureValue (MEAN)
ABCB1 Group 1Relative Change in Sitagliptin Renal Clearance (CLr)1.22 ratio
ABCB1 Group 2Relative Change in Sitagliptin Renal Clearance (CLr)0.99 ratio
ABCB1 Group 3Relative Change in Sitagliptin Renal Clearance (CLr)1.0 ratio
p-value: 0.14ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026