Pharmacokinetic Study of Pitavastatin and Ritonavir-Boosted Darunavir or Efavirenz
Condition: Hyperlipidemia; HIV
MeSH terms: Hyperlipidemias; Hyperlipoproteinemias
Study type: Interventional
Phase: Phase 1

Summary: 
      The main goal of this study is to determine how taking efavirenz affects the levels of
      pitavastatin in the bloodstream when both drugs are taken together and to see how darunavir
      with ritonavir affects the levels of pitavastatin in the bloodstream. Secondary goals are to
      see how taking pitavastatin affects the levels in the blood of efavirenz when both drugs are
      taken together and to see how taking pitavastatin affects the levels in the blood of
      darunavir.
    

Detailed description: 
      HIV infected persons are at risk for coronary heart disease due to chronic inflammation
      associated with the virus itself, the side effects of the antiretroviral (ARV) therapies
      which can cause elevated cholesterol, and the risk factors such as smoking, high blood
      pressure and family history of heart disease.

      The most commonly prescribed ARVs for treatment of HIV are efavirenz and drugs in the
      protease inhibitor (PI) class such as darunavir with ritonavir. To treat elevated cholesterol
      in patients infected with HIV, guidelines recommend the use of statins (a class of lipid
      lowering drugs). PIs and efavirenz can increase the levels of some statins and reduce the
      levels of others in the bloodstream. Pitavastatin (Livalo) is a statin approved by the Food
      and Drug Administration (FDA) for the treatment of high cholesterol.

      In order to be able to use pitavastatin safely in HIV-infected patients taking either
      darunavir with ritonavir or efavirenz, it is important to study how taking pitavastatin with
      darunavir and ritonavir or pitavastatin with efavirenz affect the levels of each of these
      drugs in the bloodstream.

      Twenty-eight participants will be enrolled in one of two study arms: 14 in Arm A and 14 in
      Arm B.

      Arm A:

      Participants will start taking pitavastatin 2 mg tablets every night at bedtime. On day 4
      participants will come in for a 14-hour pharmacokinetic (PK) overnight visit and will have
      about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood
      draw for a final blood draw. They will then stop taking pitavastatin. Participants will then
      start taking one efavirenz 600 mg tablet at bedtime.

      On day 14, participants will come in for a second 14-hour visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. Participants will then start taking both pitavastatin and efavirenz at bedtime.

      On day 18, participants will come in for a third 14-hour PK visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. They will then stop taking all study drugs and will either come in or receive a
      final phone call on day 25.

      Arm B:

      Participants will start taking one pitavastatin 2 mg tablet every morning. On day 4
      participants will come in for a 14-hour pharmacokinetic (PK) daytime visit and will have
      about 9 tablespoons of blood drawn. Participants will return 12 hours after the last blood
      draw for a final blood draw. They will then stop taking pitavastatin. Participants will then
      start taking darunavir 400 mg tablets (2) and ritonavir 100 mg tablets (1) every morning.

      On day 14, participants will come in for a second 14-hour visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. Participants will then start taking one pitavastatin 2mg tablet, two darunavir
      400 mg tablets and one ritonavir 100 mg tablet.

      On day 18, participants will come in for a third 14-hour PK visit and will have about 9
      tablespoons of blood drawn. They will return 12 hour after the last blood draw for a final
      blood draw. They will then stop taking all study drugs and will either come in or receive a
      final phone call on day 25.
    

Intervention name(s): Pitavastatin; Darunavir; Ritonavir; Efavirenz
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Pitavastatin 2 mg tablets taken at bedtime in Arm A and in the morning in Arm B.; Darunavir 400 mg tablets x 2 taken daily in Arm B; Ritonavir 100 mg tablets taken daily in Arm B; Efavirenz 600 mg tablets taken at bedtime in Arm A
Other intervention name(s): Livalo; Prezista; Norvir; Sustiva
Intervention MeSH terms: Ritonavir; Darunavir; Efavirenz; Pitavastatin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: HIV; Hyperlipidemia; Pharmacokinetics; Statins; Darunavir; Efavirenz; Pitavastatin