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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01335698
First received: April 13, 2011
Last updated: January 8, 2016
Last verified: October 2015

April 13, 2011
January 8, 2016
May 2011
September 2014   (final data collection date for primary outcome measure)
  • Number of Participants Who Died and With Adverse Events (AEs) Leading to Discontinuation, Hyperbilirubinemia, Jaundice, First-degree Arterioventricular Block, Tachycardia, and Rash [ Time Frame: Day 1 of treatment through Week 48 ] [ 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.
  • Number of Participants With A Center of Disease Control and Prevention (CDC) Class C AIDS Event [ Time Frame: Day 1 of treatment through Week 48 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 of treatment through Week 48 ] [ Designated as safety issue: Yes ]
    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-<lower limit of normal; Gr 2=11.0-15.9 mEq/L; Gr 3=8.0-10.9 mEq/L; Gr 4= <8 mEq/L. By criteria of the World Health Organization: Amylase: Gr 1=1.0-1.39*ULN; Gr 2=1.40-2.09*ULN; Gr 3.=2.10-5.0*ULN; Gr 4= >5.0*ULN.
The frequency of serious adverse events, of Adverse event (AE)s leading to discontinuation, of AEs and of laboratory abnormalities. [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01335698 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    Virologic success includes patients with HIV RNA <50 copies/mL. Two cohorts were assess: 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.
  • HIV RNA Changes From Baseline [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • CD4 Percent Changes From Baseline [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • CD4 Cell Count Changes From Baseline [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
    Last observation carried forward: missing values are replaced with the last on-treatment value in the previous visit window;if a patient does not have an on-treatment value, baseline value is carried forward. Baseline observation carried forward: missing values are replaced with the baseline value; if a patient does not have a baseline the first on-treatment value is carried forward.
  • Number of Participants With Emergent Genotypic Substitutions [ Time Frame: Baseline through Week 48 ] [ Designated as safety issue: No ]
    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
  • Proportions of subjects with HIV ribonucleic acid (RNA) < 50 c/mL and < 400 c/mL at week 48 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • ATV maximum concentration of drug (Cmax) for subjects weighing ≥ 25 - <35 kg and/or aged ≥ 6 - < 8 years [ Time Frame: 2 weeks after reaching this weight/age band ] [ Designated as safety issue: No ]
  • ATV minimum concentration of drug (Cmin) for subjects weighing ≥ 25 - <35 kg and/or aged ≥ 6 - < 8 years [ Time Frame: 2 weeks after reaching this weight/age band ] [ Designated as safety issue: No ]
  • ATV area under the curve (AUC) for subjects weighing ≥ 25 - <35 kg and/or aged ≥ 6 - < 8 years [ Time Frame: 2 weeks after reaching this weight/age band ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Phase IIIB Study Evaluating the Effects of Atazanavir Powder With Ritonavir in HIV-infected Pediatric Patients
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)
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.
Not Provided
Interventional
Phase 3
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
  • Drug: Atazanavir Sulphate
    Other Names:
    • Reyataz
    • BMS-232632
  • Drug: Ritonavir
    Other Name: Norvir
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)
Interventions:
  • Drug: Atazanavir Sulphate
  • Drug: Ritonavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
160
July 2018
September 2014   (final data collection date for primary outcome measure)

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
Both
3 Months to 11 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Brazil,   Chile,   Mexico,   Poland,   Romania,   Russian Federation,   South Africa,   Spain,   United Kingdom
Puerto Rico
 
NCT01335698
AI424-451, 2010-024537-23
Yes
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP