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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01691794
First received: September 21, 2012
Last updated: February 8, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
HIV, Pediatric
Drug: Atazanavir
Drug: Ritonavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 1 of treatment through Week 24 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4 [ Time Frame: Day 1 of treatment to Week 24 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Laboratory Test Results Meeting the Criteria for Abnormal, Grades 1-4 (Continued) [ Time Frame: Day 1 of treatment through Week 24 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 108
Study Start Date: November 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Atazanavir
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Other Name: Norvir
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: Atazanavir
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Other Name: Norvir
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: Atazanavir
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Other Name: Norvir

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691794

Locations
United States, Arizona
Phoenix Children'S Hospital
Phoenix, Arizona, United States, 85016
United States, Georgia
Grady Health System Ponce Family And Youth Clinic
Atlanta, Georgia, United States, 30322
United States, Texas
Children'S Medical Center Of Dallas
Dallas, Texas, United States, 75235
Argentina
Local Institution
Buenos Aires, Bs As, Buenos Aires, Argentina, 1141
Local Institution
Buenos Aires, Argentina, 1181
Local Institution
Buenos Aires, Argentina, 1425
Brazil
Local Institution
Salvador, Bahia, Brazil, 40110
Local Institution
Porto Alegre, Rio Grande Do Sul, Brazil, 90035
Local Institution
Sao Paulo, Brazil, 01246
Chile
Local Institution
Santiago, Metropolitana, Chile, 8207257
Local Institution
Santiago, Metropolitana, Chile, 8380418
Mexico
Local Institution
Guadalajara, Jalisco, Mexico, 44280
Local Institution
Monterrey, Nuevo Leon, Mexico, 64000
Local Institution
Merida, Yucatan, Mexico, 97000
Local Institution
Puebla, Mexico, 72000
Peru
Local Institution
Cercado, Lima, Peru, 1
Local Institution
Lima, Peru, 1
Local Institution
Lima, Peru, LIMA 10
Russian Federation
Local Institution
Moscow, Russian Federation, 129110
Local Institution
St. Petersburg, Russian Federation, 190103
South Africa
Local Institution
Port Elizabeth, Eastern Cape, South Africa, 6001
Local Institution
Bloemfontein, Free State, South Africa, 9301
Local Institution
Soweto, Gauteng, South Africa, 2013
Local Institution
Bellville, Cape Town, Western Cape, South Africa, 7530
Local Institution
Cape Town, Western Cape, South Africa, 7505
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01691794     History of Changes
Other Study ID Numbers: AI424-452  2011-003300-21 
Study First Received: September 21, 2012
Results First Received: October 27, 2015
Last Updated: February 8, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Atazanavir Sulfate
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors

ClinicalTrials.gov processed this record on May 26, 2016