PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV)
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Atazanavir powder; Ritonavir oral solution; Atazanavir capsules; Ritonavir capsules
Intervention description: Powder, oral, dosed by weight. Participants who weighed 5 to <10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to <15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to <25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.; Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.; Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.; Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Minimum age: 3 Months
Maximum age: 66 Months
Healthy volunteers: No
Keywords: HIV, Pediatric

Summary:

      The purpose of this study is to determine whether atazanavir powder combined with ritonavir
      is safe and well tolerated and produces appropriate drug exposure in children ≥3 months to <6
      years of age.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Confirmed human immunodeficiency virus (HIV)-1 infection diagnosed by a positive
             virologic test result on 2 separate occasions by:

               -  HIV DNA polymerase chain reaction

               -  HIV RNA with values ≥1,000 copies/mL

               -  Positive HIV enzyme-linked immunosorbent assay at ≥18 months of age, with
                  confirmatory Western blot or indirect immunoflourescence antibody

          -  Infants and children of either sex, aged ≥3 months to <5 years and 6 months at time of
             first treatment, and weight >5 to <25 kg with any screening baseline plasma viral load

          -  Screening plasma viral load ≥1,000 copies/mL by Roche Amplicor® HIV RNA Assay

          -  Documented genotypic and phenotypic sensitivity at screening to ATV (fold change in
             susceptibility <2.2) and to at least 2 nucleoside reverse transcriptase inhibitors
             (NRTIs) approved in the infant's country

          -  Genotypic sensitivity at screening to atazanavir (ATV) and at least 2 NRTIs

          -  Antiretroviral (ARV) treatment-naive or ARV treatment-experienced.
             Treatment-experienced participants are defined by previous exposure to ARVs through
             either prior treatment for HIV infection or through postnatal treatment with ≥1 ARV
             for the prevention of mother to child transmission. For the purposes of this study,
             participants exposed to ARVs in utero or intrapartum may be included in the study but
             will be considered treatment naive. ATV-naive participants must have genotypic
             sensitivity at screening to ATV (fold change in susceptibility <2.2) and to both
             components of the local NRTI backbone. The NRTIs must have been approved for pediatric
             use at the local country level.

        Key Exclusion Criteria:

          -  Experienced participants who received ATV or ATV/ritonavir (RTV) at any time prior to
             study enrollment or with a history of 2 or more protease inhibitor failures

          -  ARV-naïve or -experienced HIV-1 infected patients with contraindication to study
             medications syncope

          -  Family history of QTc interval syndrome, Brugada syndrome, right ventricular
             dysplasia, or a corrected QTc interval at screening of >440 ms

          -  One of the following cardiac rhythm abnormalities documented on screening
             electrocardiogram: 1st degree atrioventricular (AV) block as defined by protocol, type
             I 2nd degree AV block while awake, type II 2nd degree AV block at any time, complete
             AV block at any time, or age-adjusted heart rate <2nd percentile) History of
             pancreatitis, peripheral neuropathy, malignancy that requires systemic therapy, or any
             medical condition which, in the opinion of the investigator, added undue risk to trial
             participation

          -  Malabsorption syndrome

          -  Presence of a newly diagnosed HIV-related opportunistic infection or any medical
             condition requiring acute therapy at the time of enrollment

          -  Weight <5 or ≥25 kg at date of first dose (Day 1).

          -  >Grade 2 aspartate transaminase or alanine transaminase abnormalities

          -  Hypersensitivity to any component of the study medication formulations (ATV/RTV, or a
             locally prescribed NRTI with a pediatric indication)

          -  Infants and children of either gender <3 months or ≥5 years and 6 months at the time
             of first treatment.