Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin
Condition: HIV Infections; Hyperlipidemia
MeSH terms: Hyperlipidemias
Intervention: Pravastatin; Darunavir; Ritonavir; Pravastatin; Washout
Intervention description: Pravastatin 40 mg by mouth daily on days 1-4; Darunavir 600mg by mouth twice daily on days 12-18; Ritonavir 100mg by mouth twice daily on days 12-18; Pravastatin 40 mg by mouth daily on days 15-18; Washout (no medication) on days 5-11.
Intervention MeSH terms: Ritonavir; Darunavir; Pravastatin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV; Pravastatin; Darunavir; Ritonavir; Genetic

Summary:

      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.
    

Eligibility criteria:

        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