Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin
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ClinicalTrials.gov Identifier: NCT00630734 |
Recruitment Status
:
Completed
First Posted
: March 7, 2008
Results First Posted
: November 15, 2012
Last Update Posted
: May 22, 2014
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
HIV Infections Hyperlipidemia | Drug: Pravastatin Drug: Darunavir Drug: Ritonavir Other: Washout | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 32 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Genetic Predictors of Pharmacokinetic Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin: the Role of SLCO1B1 Polymorphisms. |
Study Start Date : | February 2008 |
Actual Primary Completion Date : | October 2009 |
Actual Study Completion Date : | September 2010 |

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.
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Drug: Pravastatin
Pravastatin 40 mg by mouth daily on days 1-4
Other Name: Pravachol
Drug: Darunavir
Darunavir 600mg by mouth twice daily on days 12-18
Other Name: Prezista
Drug: Ritonavir
Ritonavir 100mg by mouth twice daily on days 12-18
Other Name: Norvir
Drug: Pravastatin
Pravastatin 40 mg by mouth daily on days 15-18
Other Name: Pravachol
Other: Washout
Washout (no medication) on days 5-11.
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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.
|
Drug: Pravastatin
Pravastatin 40 mg by mouth daily on days 1-4
Other Name: Pravachol
Drug: Darunavir
Darunavir 600mg by mouth twice daily on days 12-18
Other Name: Prezista
Drug: Ritonavir
Ritonavir 100mg by mouth twice daily on days 12-18
Other Name: Norvir
Drug: Pravastatin
Pravastatin 40 mg by mouth daily on days 15-18
Other Name: Pravachol
Other: Washout
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.
|
Drug: Pravastatin
Pravastatin 40 mg by mouth daily on days 1-4
Other Name: Pravachol
Drug: Darunavir
Darunavir 600mg by mouth twice daily on days 12-18
Other Name: Prezista
Drug: Ritonavir
Ritonavir 100mg by mouth twice daily on days 12-18
Other Name: Norvir
Drug: Pravastatin
Pravastatin 40 mg by mouth daily on days 15-18
Other Name: Pravachol
Other: Washout
Washout (no medication) on days 5-11.
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- 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.
- 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.
- 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
- 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 ]
- 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
- 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 ]
- 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.
- 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
- 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.
- 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

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Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00630734
United States, Colorado | |
University of Colorado Denver | |
Aurora, Colorado, United States, 80045 |
Principal Investigator: | Christina L Aquilante, PharmD | University of Colorado, Denver |
Responsible Party: | University of Colorado, Denver |
ClinicalTrials.gov Identifier: | NCT00630734 History of Changes |
Other Study ID Numbers: |
07-0272 TMC114HIV4003 |
First Posted: | March 7, 2008 Key Record Dates |
Results First Posted: | November 15, 2012 |
Last Update Posted: | May 22, 2014 |
Last Verified: | May 2014 |
Keywords provided by University of Colorado, Denver:
HIV Pravastatin Darunavir Ritonavir Genetic |
Additional relevant MeSH terms:
HIV Infections Hyperlipidemias Hyperlipoproteinemias Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Ritonavir |
Darunavir Pravastatin HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Anticholesteremic Agents Hypolipidemic Agents Antimetabolites |