Safety Sudy of Atazanavir Boosted With Ritonavir in the Treatment of HIV Infection in Pediatric Patients

A Prospective Single Arm, Open-label, International, Multicenter Study to Evaluate the Safety of Atazanavir (ATV) Capsule Boosted With Ritonavir (RTV) With an Optimized NRTI Background Therapy, in HIV Infected, Antiretroviral Naive and Experienced Pediatric Subjects Greater Than or Equal to 6 Years to Less Than 18 Years

The purpose of this study is to collect safety clinical data in HIV-infected pediatric patients aged 6 and older to younger than18 years and weighing 15 kg or more, who are receiving atazanavir capsule boosted with ritonavir and an optimized nucleoside reverse transcriptase inhibitor backbone therapy as part of their antiretroviral regimen.

Study Overview

• Status: Completed
• Conditions: HIV, Pediatric
• Intervention / Treatment: Drug: Ritonavir; Drug: Atazanavir

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • Local Institution
  • Buenos Aires, Argentina, 1181
    • Local Institution
  • Buenos Aires
    • Buenos Aires, Bs As, Buenos Aires, Argentina, 1141
      • Local Institution
• Brazil
  • Sao Paulo, Brazil, 01246
    • Local Institution
  • Bahia
    • Salvador, Bahia, Brazil, 40110
      • Local Institution
    • Salvador, Bahia, Brazil, 40110-160
      • Local Institution
  • RIO Grande DO SUL
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90035-903
      • Local Institution
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035
      • Local Institution
  • SP
    • Sao Paulo, SP, Brazil, 01416-901
      • Local Institution
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile, 8380418
      • Local Institution
    • Santiago, Metropolitana, Chile, 8207257
      • Local Institution
• Mexico
  • Puebla, Mexico, 72000
    • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Local Institution
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64000
      • Local Institution
  • Yucatan
    • Merida, Yucatan, Mexico, 97000
      • Local Institution
• Peru
  • Lima, Peru, 1
    • Local Institution
  • Lima, Peru, LIMA 10
    • Local Institution
• Russian Federation
  • Moscow, Russian Federation, 129110
    • Local Institution
  • St. Petersburg, Russian Federation, 190103
    • Local Institution
• South Africa
  • Eastern CAPE
    • Port Elizabeth, Eastern CAPE, South Africa, 6001
      • Local Institution
  • FREE State
    • Bloemfontein, FREE State, South Africa, 9301
      • Local Institution
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Local Institution
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7505
      • Local Institution
    • Cape Town, Western CAPE, South Africa, 7530
      • Local Institution
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Grady Health System Ponce Family And Youth Clinic
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center of Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed HIV-1 infection diagnosed by protocol criteria
• Male or female children, ≥ 6 years to <17 years 6 months of age at the time of first treatment
• Antiretroviral-naïve or treatment-experienced participants with a detectable viral load
• Antiretroviral-naïve participants must have genotypic sensitivity at screening to atazanavir and at least 2 nucleoside reverse transcriptase inhibitors (NRTIs), which have been approved for pediatric use and dosed per local country label
• Antiretroviral-experienced participants must have documented genotypic and phenotypic sensitivity at screening to atazanavir (fold change in susceptibility <2.2) and at least 2 NRTIs, which have been approved for pediatric use and dosed per local country label.

Exclusion Criteria:

• Experienced participants who received atazanavir with or without ritonavir at any time prior to study enrollment
• Antiretroviral-naive or -experienced HIV-1 infected patients with contraindication to study medications
• Documented cardiac conduction abnormality, significant cardiac dysfunction, or a history syncope
• Family history of QTc interval syndrome, Brugada syndrome, right ventricular dysplasia, or a corrected QTc interval of >440 ms at screening

• One of the following cardiac rhythm abnormalities documented on the screening electrocardiogram:

  1. First degree atrioventricular (AV) block, as defined by protocol
  2. Type I second degree AV block while awake, type II second degree AV block at any time, complete AV block at any time, or age-adjusted heart rate <2nd percentile
• Coinfection with either hepatitis B or C virus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atazanavir, 150 mg + Ritonavir, 100 mg (weight:15 to <20 kg); Participants with baseline weight of 15 to <20 kg received 150 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.	Drug: Ritonavir; Other Names: Norvir; Drug: Atazanavir; Other Names: Reyataz; BMS-232632
Active Comparator: Atazanavir, 200 mg + Ritonavir, 100 mg (weight: 20 to <40 kg); Participants with baseline weight of 20 to <40 kg received 200 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.	Drug: Ritonavir; Other Names: Norvir; Drug: Atazanavir; Other Names: Reyataz; BMS-232632
Active Comparator: Atazanavir, 300 mg + Ritonavir, 100 mg (weight: ≥ 40 kg); Participants with baseline weight ≥ 40 kg received 300 mg of atazanavir plus 100 mg of ritonavir once daily with an optimized background therapy of 2 NRTIs for 24 weeks. In countries without locally approved pediatric indication for atazanavir, patients may continue to receive study treatment, with regular 12-week visits, until the age of 18 years.	Drug: Ritonavir; Other Names: Norvir; Drug: Atazanavir; Other Names: Reyataz; BMS-232632

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Died and With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Grade 2-4 Related AEs, Grade 3-4 AEs, and Centers for Disease Control (CDC) Class C AIDS Events	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death.	From first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)
Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4	Hematocrit (%): Grade (Gr) 1= ≥28.5- <31.5; Gr 2= ≥24- <28.5; Gr 3= ≥19.5- <24; Gr 4= <19.5. Hemoglobin (g/dL): Grade (Gr)1=8.5-10.0; Gr 2=7.5-8.4; Gr 3=6.50-7.4; Gr 4= <6.5. Platelets (/mm^3): Gr 1=100,000-124,999; Gr 2=50,000-99,999; Gr 3=25,000-49,999; Gr 4= <25,000. White blood cells (/mm^3): Gr 1=2000-2500; Gr 2=1500-1999; Gr 3=1000-1499; Gr 4= <1000. Neutrophils (/mm^3): Gr 1=1000-1500; Gr 2= ≥750-1000; Gr 3= ≥500-750; Gr 4= <500. Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) (*upper limit of normal [ULN]): Gr 1=1.5-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10.0; Gr 4= >10.0. Total bilirubin (adult and pediatric >14 days) (*ULN): Gr 1=1.1-1.5; Gr 2=1.6-2.5; Gr 3=2.6-5.0; Gr 4= >5.0. Albumin (g/dL): Gr 1= 3.1- <LLN; Gr 2=2.0-2.9; Gr 3= <2.0; Gr 4=NA. Amylase (*ULN): Gr 1=1.10-1.39; Gr 2=1.40-2.09; Gr 3=2.10-5.0; Gr 4= >5. Lipase (*ULN): Gr 1=1.1-1.5; Gr 2=1.6-3.0; Gr 3=3.1-5.0; Gr 4= >5.0.	After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)
Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4 (Continued)	Blood urea nitrogen (*upper limit of normal [ULN]): Grade (Gr) 1=1.25-2.5; Gr 2=2.6-5.0; Gr 3=5.1-10; Gr 4= >10. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12; Gr 3=12.1-15.0; Gr 4= >15.0. Bicarbonate (mEqL): Gr 1= 19.0-21.0; Gr 2=15.0-18.0; Gr 3=41-45; Gr 4= >45. Calcium, low (mg/dL): Gr 1=7.8-8.4; Gr 2=7.0-7.7; Gr 3=6.1-6.9; Gr 4= <6.1.Potassium (mEq/L), high: Gr 1=5.6-6.0; Gr 2=6.1-6.5; Gr 3=6.6-7.0; Gr 4= >7.0. Potassium (mEq/L), low: Gr 1=3.1-3.4; Gr 2=2.5-2.9; Gr 3=2.0-2.4; Gr 4= <2.0. Sodium (mEq/L), low: Gr 1=130-135; Gr 2=125-129; Gr 3=121-124; Gr 4= <1. Total cholesterol, fasting (mg/dL): Gr 1=200-239; Gr 2=240-300; Gr 3= >300; Gr 4=Not applicable (NA). Low-density lipoprotein (LDL) cholesterol, fasting (mg/dL): Gr 1=130-159; Gr 2=160-190; Gr 3= >190; Gr 4= NA. Glucose, low (mg/dL): Gr 1= 55-64; Gr 2=40-54; Gr 3=30-39; Gr 4= <30. Glucose, fasting (mg/dL): Gr 1=110-125; Gr 2=126-250; Gr 3=251-500; Gr 4 >500.	After first dose to last dose plus 30 days (assessed up to February 2017, approximately 42 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2012
• Primary Completion (Actual): October 31, 2014
• Study Completion (Actual): February 20, 2017

Study Registration Dates

• First Submitted: September 21, 2012
• First Submitted That Met QC Criteria: September 24, 2012
• First Posted (Estimate): September 25, 2012

Study Record Updates

• Last Update Posted (Actual): April 27, 2018
• Last Update Submitted That Met QC Criteria: March 30, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Atazanavir Sulfate
• Other Study ID Numbers: AI424-452; 2011-003300-21 (EudraCT Number)