The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology

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

Official Title
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The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology

Conditions
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Healthy

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: atorvastatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABCB1 Group 1<br>ABCB1 CGC/CGC genetic make-up; sitagliptin 100 mg x 1 dose; atorvastatin 40 mg x 5 doses | Drug: Sitagliptin<br>* sitagliptin 100 mg x 1 dose<br>* Other names: Januvia;Drug: atorvastatin<br>* atorvastatin 40 mg x 5 doses<br>* Other names: Lipitor;|
| Experimental: ABCB1 Group 2<br>ABCB1 CGC/TTT genetic make-up; sitagliptin 100 mg x 1 dose; atorvastatin 40 mg x 5 doses | Drug: Sitagliptin<br>* sitagliptin 100 mg x 1 dose<br>* Other names: Januvia;Drug: atorvastatin<br>* atorvastatin 40 mg x 5 doses<br>* Other names: Lipitor;|
| Experimental: ABCB1 Group 3<br>ABCB1 TTT/TTT genetic make-up; sitagliptin 100 mg x 1 dose; atorvastatin 40 mg x 5 doses | Drug: Sitagliptin<br>* sitagliptin 100 mg x 1 dose<br>* Other names: Januvia;Drug: atorvastatin<br>* atorvastatin 40 mg x 5 doses<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sitagliptin Monotherapy: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity |  | 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 | 
| Sitagliptin Monotherapy: Sitagliptin Renal Clearance (CLr) |  | 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sitagliptin + Atorvastatin: Sitagliptin Area Under the Plasma Concentration-time Curve (AUC) From 0 to Infinity |  | 0, 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy volunteers