Clinical trial NCT01099579: PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV)
Official title: A Prospective Single Arm, Open-label, International, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Atazanavir (ATV) Powder Boosted With Ritonavir (RTV) With an Optimized NRTI Background Therapy, in HIV Infected Pediatric Patients Greater Than or Equal to 3 Months to Less Than 6 Years. (Pediatric Atazanavir International Clinical Evaluation: the PRINCE I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: HIV, Pediatric
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-04-07
Enrollment: 82
Sex: ALL
Minimum age (years): 3
Maximum age (years): 66
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation
timeFrame: From Day 1 to Week 48
measure: Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4
timeFrame: After Day 1 to Week 48
measure: Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48
timeFrame: From Baseline to Week 48
measure: Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events
timeFrame: From Day 1 to Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight
timeFrame: At Week 48
measure: Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status
timeFrame: From Day 1 to Week 48
measure: Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight
timeFrame: From Baseline to Week 48
measure: Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status
timeFrame: From Baseline to Week 48
measure: CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight
timeFrame: From Baseline to Week 48
measure: CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status
timeFrame: From Baseline to Week 48
measure: Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight
timeFrame: From Baseline to Week 48
measure: Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status
timeFrame: From Baseline to Week 48
measure: Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir
timeFrame: After Day 1 to Week 48
measure: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir
timeFrame: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
measure: Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir
timeFrame: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
measure: Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir
timeFrame: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
measure: Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir
timeFrame: At Week 2
measure: Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir
timeFrame: At Week 2
Other outcomes:
Locations:
city: Sao Paolo
country: Brazil
facility: Local Institution
state: SAO Paulo
city: Santiago
country: Chile
facility: Local Institution
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution
state: Metropolitana
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Oaxaca
country: Mexico
facility: Local Institution
city: Puebla
country: Mexico
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Bloemfontein
country: South Africa
facility: Local Institution
state: FREE State
city: Coronationville
country: South Africa
facility: Local Institution
state: Gauteng
city: Soweto
country: South Africa
facility: Local Institution
state: Gauteng
city: Congella
country: South Africa
facility: Local Institution
state: KWA ZULU Natal
city: Cape Town
country: South Africa
facility: Local Institution
state: Western CAPE
city: Bangkok
country: Thailand
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: