Drug Interactions Between Voriconazole and Atazanavir Coadministered as Atazanavir/Ritonavir in Healthy Participants
Condition: Human Immunodeficiency Virus Type 1 (HIV-1); HIV Infections
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome
Intervention: Voriconazole; Atazanavir; Ritonavir
Intervention description: Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.; Treatment B in EM participants: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Treatment B in participants who were poor metabolizers of CYP2C19 (PMs): PM participants received oral tablets of atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.; Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.
Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate; Voriconazole
Phase: Phase 1
Study type: Interventional
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 185.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study assesses the effects of voriconazole, 200 mg, administered twice daily (BID), on
      the steady-state pharmacokinetics of atazanavir administered as atazanavir/ritonavir, 300/100
      mg once daily (QD), in healthy participants with functional CYP2C19 alleles. The study also
      reviews the effects of atazanavir/ritonavir, 300/100 mg QD, on the pharmacokinetics of
      voriconazole, 200 mg, BID in healthy participants with functional CYP2C19 alleles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy participants as determined by no clinically significant deviation from normal

          -  Body Mass Index (BMI) of 18 to 32 kg/m^2, inclusive. BMI=weight(kg)/height (m)^2

          -  Women who are not of childbearing potential (WOCBP)(ie, who are postmenopausal or
             surgically sterile) and men, ages 18 to 45 years, inclusive

        Exclusion Criteria:

          -  WOCBP

          -  Sexually active fertile men not using effective birth control if their partners are
             WOCBP

          -  Proven or suspected acute hepatitis (within 12 months prior to the 1st dose)

          -  Any significant acute or chronic medical illness

          -  Any gastrointestinal surgery that could impact on the absorption of study drug

          -  Smoking more than 5 cigarettes per day

          -  History of any hemolytic disorders (including drug-induced hemolysis)

          -  History of acute or chronic pancreatitis

          -  History of hypochlorhydria or achlorhydria

          -  Men and women weighing <40 kg

          -  Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1
             or HIV-2 antibody

          -  Patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose
             malabsorption