- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00630734
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
Status
Completed
Conditions
Intervention / Treatment
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
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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:
Darunavir 600mg by mouth twice daily on days 12-18
Other Names:
Ritonavir 100mg by mouth twice daily on days 12-18
Other Names:
Pravastatin 40 mg by mouth daily on days 15-18
Other Names:
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:
Darunavir 600mg by mouth twice daily on days 12-18
Other Names:
Ritonavir 100mg by mouth twice daily on days 12-18
Other Names:
Pravastatin 40 mg by mouth daily on days 15-18
Other Names:
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:
Darunavir 600mg by mouth twice daily on days 12-18
Other Names:
Ritonavir 100mg by mouth twice daily on days 12-18
Other Names:
Pravastatin 40 mg by mouth daily on days 15-18
Other Names:
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
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Lipid Metabolism Disorders
- Dyslipidemias
- Hyperlipidemias
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Antimetabolites
- Protease Inhibitors
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Ritonavir
- Pravastatin
- Darunavir
Other Study ID Numbers
- 07-0272
- TMC114HIV4003
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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