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

NCT01691794 | Completed Phase 4 Results

• 2 other identifiers: AI424-4522011-003300-21
• Study Type: interventional
• Target: 108
• Locations: 8 countries
• Sites: 27

Brief Summary

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.

Conditions

HIV, Pediatric

Outcome Measures

Primary Outcomes (3)

• 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)

Study Arms (3)

Atazanavir, 150 mg + Ritonavir, 100 mg (weight:15 to <20 kg)

ACTIVE COMPARATOR

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; Drug: Ritonavir

Atazanavir, 200 mg + Ritonavir, 100 mg (weight: 20 to <40 kg)

ACTIVE COMPARATOR

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; Drug: Ritonavir

Atazanavir, 300 mg + Ritonavir, 100 mg (weight: ≥ 40 kg)

ACTIVE COMPARATOR

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; Drug: Ritonavir

Interventions

Atazanavir DRUG

Also known as: Reyataz, BMS-232632

Atazanavir, 150 mg + Ritonavir, 100 mg (weight:15 to <20 kg); Atazanavir, 200 mg + Ritonavir, 100 mg (weight: 20 to <40 kg); Atazanavir, 300 mg + Ritonavir, 100 mg (weight: ≥ 40 kg)

Ritonavir DRUG

Also known as: Norvir

Atazanavir, 150 mg + Ritonavir, 100 mg (weight:15 to <20 kg); Atazanavir, 200 mg + Ritonavir, 100 mg (weight: 20 to <40 kg); Atazanavir, 300 mg + Ritonavir, 100 mg (weight: ≥ 40 kg)

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• First degree atrioventricular (AV) block, as defined by protocol
• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (27)

Phoenix Children'S Hospital

Phoenix, Arizona, 85016, United States

Location

Grady Health System Ponce Family And Youth Clinic

Atlanta, Georgia, 30322, United States

Location

Children'S Medical Center Of Dallas

Dallas, Texas, 75235, United States

Location

Local Institution

Buenos Aires, Bs As, Buenos Aires, 1141, Argentina

Location

Local Institution

Buenos Aires, 1181, Argentina

Location

Local Institution

Buenos Aires, 1425, Argentina

Location

Local Institution

Salvador, Estado de Bahia, 40110-160, Brazil

Location

Local Institution

Salvador, Estado de Bahia, 40110, Brazil

Location

Local Institution

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Local Institution

Porto Alegre, Rio Grande do Sul, 90035, Brazil

Location

Local Institution

São Paulo, São Paulo, 01416-901, Brazil

Location

Local Institution

São Paulo, 01246, Brazil

Location

Local Institution

Santiago, Santiago Metropolitan, 8207257, Chile

Location

Local Institution

Santiago, Santiago Metropolitan, 8380418, Chile

Location

Local Institution

Guadalajara, Jalisco, 44280, Mexico

Location

Local Institution

Monterrey, Nuevo León, 64000, Mexico

Location

Local Institution

Mérida, Yucatán, 97000, Mexico

Location

Local Institution

Puebla City, 72000, Mexico

Location

Local Institution

Lima, 1, Peru

Location

Local Institution

Lima, LIMA 10, Peru

Location

Local Institution

Moscow, 129110, Russia

Location

Local Institution

Saint Petersburg, 190103, Russia

Location

Local Institution

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Local Institution

Bloemfontein, Free State, 9301, South Africa

Location

Local Institution

Soweto, Gauteng, 2013, South Africa

Location

Local Institution

Cape Town, Western Cape, 7505, South Africa

Location

Local Institution

Cape Town, Western Cape, 7530, South Africa

Location

Related Links

• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• BMS clinical trial educational resource

MeSH Terms

Interventions

Atazanavir Sulfate; Ritonavir

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: September 25, 2012
• Study Start: November 30, 2012
• Primary Completion: October 31, 2014
• Study Completion: February 20, 2017
• Last Updated: April 27, 2018
• Results First Posted: November 30, 2015

Record last verified: 2018-03

Locations

ZA (5); ME (4); AR (3); RU (2); CL (2); PE (2); US (3); BR (6)