Official Title: “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 Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Crossover Assignment, Pharmacokinetics Study

Study Primary Completion Date: March 2009

Intervention(s) in this Clinical Trial

• Drug: Pravastatin, darunavir, ritonavir
  • Days 1-4: Pravastatin 40 mg QD; Days 5-11: Washout; Days 12-14: Darunavir 600mg/Ritonavir 100mg BID Days 15-18: Darunavir 600mg/Ritonavir 100 mg BID + Pravastatin 40 mg QD

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A

Primary Measures

• Change in pravastatin AUC when pravastatin is administered with and without darunavir/ritonavir.
  • Time Frame: multiple dose pravastatin (4 days)
    Safety Issue?: No

Secondary Measures

• Change in pravastatin Cmax, tmax, t1/2, and oral clearance when pravastatin is administered with and without darunavir/ritonavir.
  • Time Frame: multiple dose pravastatin (4 days)
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Colorado at Denver and Health Sciences Center

Overall Clinical Trial Officials and Contacts

Christina L Aquilante, PharmD Principal Investigator University of Colorado Denver and Health Sciences Center  

Overall Contact: Christina L Aquilante, PharmD 303-315-3119 christina.aquilante@uchsc.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00630734

Study ID Number: COMIRB07-0272

ClinicalTrials.gov Identifier: NCT00630734

Health Authority: United States: Food and Drug Administration