The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology - Full Text View

Purpose

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

Condition	Intervention	Phase
Healthy	Drug: Sitagliptin Drug: atorvastatin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label
Official Title:	The Role of P-glycoprotein in Sitagliptin Clinical Pharmacology

Resource links provided by NLM:

Drug Information available for: Atorvastatin calcium Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Other Outcome Measures:

Relative Change in 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 ] [ Designated as safety issue: No ]
AUC of sitagliptin when administered with atorvastatin divided by AUC of sitagliptin when administered alone
Relative Change in 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 ] [ Designated as safety issue: No ]
Cmax of sitagliptin when administered with atorvastatin divided by Cmax of sitagliptin when administered alone
Relative Change in Sitagliptin Renal Clearance (CLr) [ Time Frame: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24 hours ] [ Designated as safety issue: Yes ]
CLr of sitagliptin when administered with atorvastatin divided by CLr of sitagliptin when administered alone
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Enrollment:	33
Study Start Date:	November 2009
Study Completion Date:	July 2011
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ABCB1 Group 1 ABCB1 CGC/CGC genetic make-up; sitagliptin 100 mg x 1 dose; atorvastatin 40 mg x 5 doses	Drug: Sitagliptin sitagliptin 100 mg x 1 dose Other Name: Januvia Drug: atorvastatin atorvastatin 40 mg x 5 doses Other Name: Lipitor
Experimental: ABCB1 Group 2 ABCB1 CGC/TTT genetic make-up; sitagliptin 100 mg x 1 dose; atorvastatin 40 mg x 5 doses	Drug: Sitagliptin sitagliptin 100 mg x 1 dose Other Name: Januvia Drug: atorvastatin atorvastatin 40 mg x 5 doses Other Name: Lipitor
Experimental: ABCB1 Group 3 ABCB1 TTT/TTT genetic make-up; sitagliptin 100 mg x 1 dose; atorvastatin 40 mg x 5 doses	Drug: Sitagliptin sitagliptin 100 mg x 1 dose Other Name: Januvia Drug: atorvastatin atorvastatin 40 mg x 5 doses Other Name: Lipitor

Eligibility

Ages Eligible for Study:	21 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01112670

Locations

United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045

Sponsors and Collaborators

University of Colorado, Denver

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:

Christina L Aquilante, PharmD

University of Colorado, Denver

More Information

No publications provided

Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT01112670 History of Changes
Other Study ID Numbers:	09-0531, R03DK084089
Study First Received:	April 26, 2010
Results First Received:	October 7, 2012
Last Updated:	January 22, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:

Healthy volunteers

Additional relevant MeSH terms:

Krestin
Atorvastatin
Sitagliptin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers

Radiation-Protective Agents
Protective Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Hypoglycemic Agents

ClinicalTrials.gov processed this record on May 21, 2013