Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin

May 20, 2014 updated by: University of Colorado, Denver

Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms.

Pravastatin (Pravachol) is approved by the Food and Drug Administration (FDA) and is used to treat high cholesterol. Darunavir (Prezista) and ritonavir (Norvir) are approved by the Food and Drug Administration (FDA) to treat HIV infection. When darunavir and ritonavir are given with pravastatin, they can increase the blood levels of pravastatin. The degree of this interaction varies from person to person. The way that darunavir and ritonavir interact with pravastatin may be affected by a person's genetic make-up. Genetic factors (or DNA) are those that people are born with and that make each person unique. Genetic differences are the reason why one person's body traits such as height and hair color are different from another person's body traits. Genetic differences can also affect the way a medication works in the body or the way two medications interact in the body. The purpose of this clinical study is to determine if a person's genetic make-up affects the way darunavir and ritonavir interact with pravastatin in the body.

Study Overview

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy, HIV-negative volunteers

Exclusion Criteria:

  • Currently active or chronic cardiovascular, hepatic, renal, pancreatic, gastrointestinal, neurologic, hematologic, psychiatric, metabolic, respiratory, inflammatory, or infectious disease
  • Chronic pancreatitis
  • History of rhabdomyolysis
  • History of statin-associated myopathy
  • Active malignancy
  • History of significant skin disease, food allergy, drug allergy, dermatitis, eczema, psoriasis
  • Pregnancy/breastfeeding
  • HIV positive and/or AIDS
  • serum creatinine grade 1 or greater (≥ 1.1 x upper limit of laboratory normal range [ULN]);
  • hemoglobin grade 1 or greater (≤ 10.9 g/dL);
  • platelet count grade 1 or greater (≤ 124.999 x 109/L);
  • absolute neutrophil count grade 1 or greater (≤ 1.3 x 109/L);
  • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) grade 1 or greater (≥ 1.25 x ULN);
  • total bilirubin grade 1 or greater (≥ 1.1 x ULN)
  • serum lipase grade 1 or greater (≥ 1.1 x ULN)
  • serum amylase grade 1 or greater (≥ 1.1 x ULN)
  • any other laboratory abnormality of grade 2 or above

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SLCO1B1 Group 1
Participants with the SLCO1B1 *1A/*1A diplotype; Interventions: pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18.
Pravastatin 40 mg by mouth daily on days 1-4
Other Names:
  • Pravachol
Darunavir 600mg by mouth twice daily on days 12-18
Other Names:
  • Prezista
Ritonavir 100mg by mouth twice daily on days 12-18
Other Names:
  • Norvir
Pravastatin 40 mg by mouth daily on days 15-18
Other Names:
  • Pravachol
Washout (no medication) on days 5-11.
Experimental: SLCO1B1 Group 2
Participants with the SLCO1B1 *1A/*1B or *1B/*1B diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18.
Pravastatin 40 mg by mouth daily on days 1-4
Other Names:
  • Pravachol
Darunavir 600mg by mouth twice daily on days 12-18
Other Names:
  • Prezista
Ritonavir 100mg by mouth twice daily on days 12-18
Other Names:
  • Norvir
Pravastatin 40 mg by mouth daily on days 15-18
Other Names:
  • Pravachol
Washout (no medication) on days 5-11.
Experimental: SLCO1B1 Group 3
Participants who carry at least one SLCO1B1 *5, *15, or *17 diplotype; Interventions: Pravastatin 40 mg by mouth once daily on days 1-4, washout on days 5-11, darunavir 600 mg and ritonavir 100 mg by mouth twice daily on days 12-18, pravastatin 40 mg by mouth once daily on days 15-18.
Pravastatin 40 mg by mouth daily on days 1-4
Other Names:
  • Pravachol
Darunavir 600mg by mouth twice daily on days 12-18
Other Names:
  • Prezista
Ritonavir 100mg by mouth twice daily on days 12-18
Other Names:
  • Norvir
Pravastatin 40 mg by mouth daily on days 15-18
Other Names:
  • Pravachol
Washout (no medication) on days 5-11.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative Change in Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
AUC of pravastatin when administered with darunavir/ritonavir divided by AUC of pravastatin when administered alone. The AUC was measured over a 24-hour dosing interval.
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Relative Change in Pravastatin Maximum Plasma Concentration (Cmax)
Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Cmax of pravastatin when administered with darunavir/ritonavir divided by the Cmax of pravastatin when administered alone.
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pravastatin Alone: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Dosing interval of 24 hours
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin Alone: Pravastatin Maximum Plasma Concentration (Cmax)
Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin + Darunavir/Ritonavir: Pravastatin Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Dosing interval of 24 hours
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
Pravastatin + Darunavir/Ritonavir: Pravastatin Maximum Plasma Concentration (Cmax)
Time Frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose
0, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24 hours post-dose

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Darunavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
AUC of darunavir over a 12-hour dosing interval.
0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Darunavir Maximum Plasma Concentration (Cmax)
Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Cmax of darunavir over a 12-hour dosing interval
0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Ritonavir Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval
Time Frame: 0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
AUC of ritonavir over a 12-hour dosing interval.
0, 1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Ritonavir Maximum Plasma Concentration (Cmax)
Time Frame: 0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose
Cmax of ritonavir over a 12-hour dosing interval
0,1, 2, 3, 4, 5, 6, 8, 12 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

October 1, 2009

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

February 28, 2008

First Submitted That Met QC Criteria

March 6, 2008

First Posted (Estimate)

March 7, 2008

Study Record Updates

Last Update Posted (Estimate)

May 22, 2014

Last Update Submitted That Met QC Criteria

May 20, 2014

Last Verified

May 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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