Clinical Trials

MainTitle

Phase IIIB Study Evaluating the Effects of Atazanavir Powder With Ritonavir in HIV-infected Pediatric Patients (PRINCE2)

This study has been completed
Sponsor
Bristol-Myers Squibb


Information provided by (Responsible Party)
Bristol-Myers Squibb
ClinicalTrials.gov Identifier
NCT01335698

First received: April 13, 2011
Last updated: October 11, 2018
Last Verified: October 2018
History of Changes
Purpose

Purpose

The purpose of this study is to describe the safety, efficacy, and pharmacokinetics of a regimen of atazanavir powder boosted with ritonavir and an optimized dual nucleoside reverse transcriptase inhibitor in pediatric patients aged ≥3 months to <11 years.

Condition Intervention Phase
HIV

Drug : Atazanavir Sulphate
Drug : Ritonavir
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Human Immunodeficiency Virus (HIV) Infected, Antiretroviral, Naive and Experienced Pediatric Subjects From 3 Months to Less Than 11 Years.(Pediatric Atazanavir International Clinical Evaluation: the PRINCE II Study)

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures

  • Number of Participants Who Died and With Adverse Events (AEs) Leading to Discontinuation, Hyperbilirubinemia, Jaundice, First-degree Arterioventricular Block, Tachycardia, and Rash on ATV Powder [ Time Frame: Day one to week 300 (approximately 22-Jan-2018) ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
  • Number of Participants Who Experienced a SAE on ATV Powder [ Time Frame: Day one to week 300 (approximately 22-Jan-2018) ]
    SAE= any of the the following: is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event (defined as a medical event(s) that may not be immediately life threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the subject or may require intervention [eg, medical, surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples of such events include, but are not limited to, intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization
  • Number of Participants With A Center of Disease Control and Prevention (CDC) Class C AIDS Event on ATV Powder [ Time Frame: Day one to week 300 (approximately 22-Jan-2018) ]
    The CDC disease staging system assesses the severity of HIV disease by CD4 cell counts and by the presence of specific HIV-related conditions. CD4 counts are classified as 1: ≥500 cells/µL, 2: 200-499 cells/µL, and 3: <200 cells/µL. Children with HIV infection are also classified in each of several categories. Category N: Not symptomatic. Category A: Mildly symptomatic. Category B: Moderately symptomatic. Category C: Severely symptomatic.
  • Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality on ATV Powder [ Time Frame: Day one to week 300 (approximately 22-Jan-2018) ]
    Criteria of the Division of AIDS for grading the severity of adult and pediatric adverse events as follows: Grade (Gr) 1=mild; Gr 2=moderate; Gr 3=severe; Gr 4=potentially life-threatening. Neutrophils (absolute) (adult and infants >7 days): Gr 1=1.000-1300/mm^3; Gr 2=750-999 mm^3; Gr 3=500-749 mm^3; Gr 4= <500 mm^3. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase: Gr 1=1.25-2.5*upper limit of normal (ULN); Gr 2=2.6-5.0*ULN; Gr 3=5.1-10.0*ULN; Gr 4= >10.0*ULN. Bilirubin, total (adults and infants >14 days): Gr 1=1.1-1.5*ULN; Gr 2=1.6-2.5*ULN; Gr 3=2.6-5.0*ULN; Gr 4= >5.0*ULN. Lipase: Gr 1=1.1-1.5*ULN; Gr 2=1.6-3.0*ULN; Gr 3=3.1-5.0*ULN; Gr 4= >5.0*ULN. Bicarbonate, serum low: Gr 1=16.0 mEq/L-5.0*ULN.
Secondary Outcome Measures:
  • Number of Participants With HIV RNA <50 Copies/mL and <400 Copies/mL in the Week 24 Atazanavir Powder Cohort and the Eligible Week 48 Atazanavir Powder Cohort [ Time Frame: Day 1 of treatment to weeks 24 and 48 ]
    Virologic success includes patients with HIV RNA <50 copies/mL. Two cohorts were assessed: The Atazanavir Powder Cohort=patients who received treatment and did not switch to capsule before analysis Week 24 or before their HIV RNA Week 24 assessment, and the Eligible Week 48 Atazanavir Powder Cohort=patients who initiated study treatment at least 48 weeks before last person last visit and did not switch to capsule before analysis Week 48 or before their HIV RNA Week 48 assessment.
  • Mean Change From Baseline in HIV RNA on ATV Powder [ Time Frame: Baseline to Weeks 24 and 48 ]
    Human immunodeficiency virus ribonucleic acid (HIV RNA) change from baseline using observed values
  • Mean Change From Baseline in CD4 Percent on ATV Powder [ Time Frame: Baseline to Weeks 24 and 48 ]
    Change in CD4 percent using observed values
  • CD4 Cell Count Changes From Baseline on ATV Powder [ Time Frame: Baseline to Weeks 24 and 48 ]
    CD4 cell count change from baseline using observed values
  • Number of Participants With Emergent Genotypic Substitutions on ATV Powder Through Week 48 [ Time Frame: Baseline through Week 48 ]
    Newly emergent substitutions are on-treatment substitutions that were not detected at baseline.Viral rebound in the resistance analysis was defined as: Less than a 1 log10 drop from baseline in plasma HIV RNA level by Week 16, confirmed by a second plasma HIV RNA level redrawn within 2 and 4 weeks from original sample. Or, a plasma HIV RNA level >200 c/mL after Week 24, confirmed by a second plasma HIV RNA level redrawn within 2 and 4 weeks from original sample. Or, repeated plasma HIV RNA level ≥50 c/mL after Week 48. Viral rebound was defined as a plasma HIV RNA level ≥400 c/mL at any time in a patient who had previously achieved a plasma HIV RNA level <50 c/mL. Or, a plasma HIV RNA level ≥50 c/mL and <1,000 c/mL followed by a return to virologic suppression was considered a viral blip and not a viral rebound. NRTI=nucleoside reverse transcriptase inhibitor
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Baseline to Week 2 ]
    To describe the PK profile of ATV powder formulation with RTV in pediatric subjects weighing 25 - < 35 kg and/or 6 to < 11 years of age and for the new 5 - < 10 kg cohort (200 mg ATV and 80 mg RTV) in terms of ATV Cmax
  • Minimum Plasma Concentration (Cmin) [ Time Frame: Baseline to Week 2 ]
    To describe the PK profile of ATV powder formulation with RTV in pediatric subjects weighing 25 - < 35 kg and/or 6 to < 11 years of age and for the new 5 - < 10 kg cohort (200 mg ATV and 80 mg RTV) in terms of ATV Cmin
  • Area Under the Concentration-Time Curve [AUC(TAU)] [ Time Frame: Baseline to Week 2 ]
    To describe the PK profile of ATV powder formulation with RTV in pediatric subjects weighing 25 - < 35 kg and/or 6 to < 11 years of age and for the new 5 - < 10 kg cohort (200 mg ATV and 80 mg RTV) in terms of ATV AUC

Enrollment: 160
Study Start Date: May 27, 2011
Study Completion Date: January 22, 2018
Primary Completion Date: September 10, 2014 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Stage 1: Atazanavir + Ritonavir
Participants received atazanavir powder orally (dosed by weight: 5 to <10 kg=150 mg, 5 to <10 kg=200 mg, 10 to <15 kg=200 mg, 15 to <25 kg=250 mg, 25 to <35 kg=300 mg) once daily for 24 to 48 weeks or a weight ≥35 kg. Participants also received ritonavir once daily for 24 to 48 weeks or weight ≥35 kg in the form of 80-mg/mL solution, orally (dosed by weight 5 to <25 kg=80 mg, 25 to <35 kg=100 mg); 100-mg capsule, orally (dosed by weight 25 to <35 kg=100 mg); or 100-mg tablet, orally (dosed by weight 25 to <35 kg=100 mg)
Drug: Atazanavir Sulphate
Other Name:
  • Reyataz
  • BMS-232632

Drug: Ritonavir
Other Name: Norvir
Eligibility

Eligibility

Ages Eligible for Study: 3 Months to 11 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com
Key Inclusion Criteria:

  • Confirmed HIV-1 infection diagnosed by protocol criteria
  • Screening HIV RNA level ≥1000 copies/mL
  • ≥3 months to <11 years of age at time of first treatment
  • Antiretroviral-naive or -experienced
  • At screening, all participants must have genotypic sensitivity to atazanavir and at least 2 nucleoside reverse transcriptase inhibitors (NRTIs), which must be approved for pediatric use at the local country.
  • Antiretroviral-experienced patients must also have documented phenotypic sensitivity at screening to atazanavir (Fold Change in susceptibility <2.2) and to at least 2 NRTIs that are approved in their country

  • Key

Exclusion Criteria:
  • Experienced participants who received atazanavir or atazanavir/ritonavir at any time prior to study enrollment or who have a history of 2 or more protease inhibitor failures
  • Antiretroviral-naïve or -experienced HIV-1-infected patients with contraindication to study medications
  • Cardiac rhythm abnormalities
  • Need for tenofovir
  • Weight <5 or ≥35kg
  • >Grade 2 abnormality in aspartate transaminase/alanine transaminase levels
  • Coinfection with either hepatitis B or C virus
  • Any active Centers for Disease Control and Prevention Category C clinical condition

contacts and locations

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: NCT01335698

Locations

United States, District of Columbia
Children'S National Medical Center
Washington, District of Columbia, United States, 20010
United States, New York
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
Argentina
Local Institution
Buenos Aires, Bs As, Buenos Aires, Argentina, 1141
Local Institution
Bunos Aires, Buenos Aires, Argentina, 1425
Brazil
Local Institution
Recife, Pernambuco, Brazil, 50070-500
Local Institution
Porto Alegre, RIO Grande DO SUL, Brazil, 90020-090
Local Institution
Porto Alegre, RIO Grande DO SUL, Brazil, 90035-903
Local Institution
Ribeirao Preto, SAO Paulo, Brazil, 14049-900
Chile
Local Institution
Santiago, Metropolitana, Chile, 8380418
Local Institution
Santiago, Metropolitana, Chile
Mexico
Local Institution
Df, Distrito Federal, Mexico, 06720
Local Institution
Guadalajara, Jalisco, Mexico, 44160
Local Institution
Guadalajara, Jalisco, Mexico, 44280
Local Institution
Merida, Yucatan, Mexico, 97000
Local Institution
Oaxaca, Mexico, 71256
Local Institution
Puebla, Mexico, 72000
Poland
Local Institution
Warszawa, Poland, 01-201
Romania
Local Institution
Bucharest, Romania, 72205
Russian Federation
Local Institution
Smolensk, Russian Federation, 214006
Local Institution
St. Petersburg, Russian Federation, 189635
Local Institution
St.petersburg, Russian Federation, 198103
South Africa
Local Institution
Port Elizabeth, Eastern CAPE, South Africa, 6001
Local Institution
Port Elizabeth, Eastern CAPE, South Africa, 6014
Local Institution
Bloemfontein, FREE State, South Africa, 9301
Local Institution
Benoni, Gauteng, South Africa, 1501
Local Institution
Coronationville, Gauteng, South Africa, 2092
Local Institution
Pretoria, Gauteng, South Africa, 0001
Local Institution
Soweto, Gauteng, South Africa, 2001
Local Institution
Parrow Valley, Western CAPE, South Africa, 7505
Spain
Local Institution
Barcelona, Spain, 08950
Local Institution
Madrid, Spain, 28041
United Kingdom
Local Institution
Birmingham, WEST Midlands, United Kingdom, B9 5ST

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information

More Information

Additional Information:

BMS Clinical Trial Patient Recruiting

Additional Information:

Investigator Inquiry Form

Responsible Party: Bristol-Myers Squibb  
ClinicalTrials.gov Identifier: NCT01335698   History of Changes  
Other Study ID Numbers: AI424-451  
  2010-024537-23  
Study First Received: April 13, 2011  
Last Updated: October 11, 2018  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Bristol-Myers Squibb:

Pediatric

Additional relevant MeSH terms:
Ritonavir
Atazanavir Sulfate

ClinicalTrials.gov processed this data on September 16, 2019
This information is provided by ClinicalTrials.gov.