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PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV) (PRINCE1)

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Atazanavir powder
Ritonavir oral solution
Atazanavir capsules
Ritonavir capsules
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, Pediatric

Eligibility Criteria

3 Months - 66 Months (Child)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Confirmed human immunodeficiency virus (HIV)-1 infection diagnosed by a positive virologic test result on 2 separate occasions by:

    • HIV DNA polymerase chain reaction
    • HIV RNA with values ≥1,000 copies/mL
    • Positive HIV enzyme-linked immunosorbent assay at ≥18 months of age, with confirmatory Western blot or indirect immunoflourescence antibody
  • Infants and children of either sex, aged ≥3 months to <5 years and 6 months at time of first treatment, and weight >5 to <25 kg with any screening baseline plasma viral load
  • Screening plasma viral load ≥1,000 copies/mL by Roche Amplicor® HIV RNA Assay
  • Documented genotypic and phenotypic sensitivity at screening to ATV (fold change in susceptibility <2.2) and to at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) approved in the infant's country
  • Genotypic sensitivity at screening to atazanavir (ATV) and at least 2 NRTIs
  • Antiretroviral (ARV) treatment-naive or ARV treatment-experienced. Treatment-experienced participants are defined by previous exposure to ARVs through either prior treatment for HIV infection or through postnatal treatment with ≥1 ARV for the prevention of mother to child transmission. For the purposes of this study, participants exposed to ARVs in utero or intrapartum may be included in the study but will be considered treatment naive. ATV-naive participants must have genotypic sensitivity at screening to ATV (fold change in susceptibility <2.2) and to both components of the local NRTI backbone. The NRTIs must have been approved for pediatric use at the local country level.

Key Exclusion Criteria:

  • Experienced participants who received ATV or ATV/ritonavir (RTV) at any time prior to study enrollment or with a history of 2 or more protease inhibitor failures
  • ARV-naïve or -experienced HIV-1 infected patients with contraindication to study medications syncope
  • Family history of QTc interval syndrome, Brugada syndrome, right ventricular dysplasia, or a corrected QTc interval at screening of >440 ms
  • One of the following cardiac rhythm abnormalities documented on screening electrocardiogram: 1st degree atrioventricular (AV) block as defined by protocol, type I 2nd degree AV block while awake, type II 2nd degree AV block at any time, complete AV block at any time, or age-adjusted heart rate <2nd percentile) History of pancreatitis, peripheral neuropathy, malignancy that requires systemic therapy, or any medical condition which, in the opinion of the investigator, added undue risk to trial participation
  • Malabsorption syndrome
  • Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment
  • Weight <5 or ≥25 kg at date of first dose (Day 1).
  • >Grade 2 aspartate transaminase or alanine transaminase abnormalities
  • Hypersensitivity to any component of the study medication formulations (ATV/RTV, or a locally prescribed NRTI with a pediatric indication)
  • Infants and children of either gender <3 months or ≥5 years and 6 months at the time of first treatment.

Sites / Locations

  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Atazanavir powder, 150 mg/Ritonavir oral solution, 80 mg

Atazanavir powder, 200 mg/Ritonavir oral solution, 80 mg

Atazanavir powder, 250 mg/Ritonavir oral solution, 80 mg

Arm Description

Patients weighing 5 to <10 kg received atazanavir (ATV), 150-mg powder dosed in 50-mg packets, and ritonavir (RTV) oral solution, 80 mg. Stage 1: Initial dose was determined by patient's weight on the day of first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage. All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Patients weighing 10 to <15 kg received ATV powder, 200 mg, dosed in 50-mg sachet packets and RTV oral solution, 80 mg. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Patients weighing 15 to <25 kg received 250 mg of ATV powder dosed in 50-mg sachet packets, with 80 mg of RTV solution. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from powder to the capsule formulation of ATV. Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.

Outcomes

Primary Outcome Measures

Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation
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.
Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4
ALT=alanine aminotransferase; SGPT=serum glutamic-pyruvic transaminase; AST=aspartate aminotransferase; SGOT=serum glutamic-oxaloacetic transaminase; ULN=upper limit of normal. Grading by the National Institute of Health Division of AIDs and World Health Organization criteria. Hemoglobin (g/dL): Grade (Gr)1=9.5-11.0; Gr 2=8.0-9.4; Gr 3=6.5-7.9; Gr 4=<6.5. Neutrophils, absolute (/mm^3): Gr 1=>=1000-<1500; Gr 2= >=750-<1000; Gr 3=>=500-<750; Gr 4=<500. ALT/SGPT (*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=>10. AST/SGOT (*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=>10. Alkaline phosphatase(*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5: Gr 3=5.1-10; Gr 4=>10. Total bilirubin (*ULN): Gr 1=1.1-1; Gr 2=1.6-2.5; Gr 3=2.6-5; Gr 4=>5. Amylase (*ULN): Gr 1=1.10-39; Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=>5.0. Lipase (*ULN): Gr 1=1.10-1.39: Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=>5.0. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12.0; Gr 3=12.1-15.0; Gr 4=>15.
Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48
Electrocardiogram parameters were measured at baseline for QTC Bazett, QTC Fridericia, and PR interval. The mean change from baseline at week 48 is reported by arm in milliseconds.
Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events
CDC Class C events are AIDS-defining events that include recurrent bacterial pneumonia (>=2 episodes in 12 months); candidiasis of the bronchi, trachea, lungs, or esophagus; invasive cervical carcinoma; disseminated or extrapulmonary coccidioidomycosis; extrapulmonary cryptococcosis; chronic intestinal cryptosporidiosis (>1 month); cytomegalovirus disease; HIV-related encephalopathy; herpes simplex: chronic ulcers, or bronchitis, pneumonitis, or esophagitis; disseminated or extrapulmonary histoplasmosis; chronic intestinal isosporiasis; Kaposi sarcoma; immunoblastic or primary brain Burkitt lymphoma; mycobacterium avium complex, kansasii, or tuberculosis; mycobacterium, other species; Pneumocystis carinii pneumonia; progressive multifocal leukoencephalopathy; Salmonella septicemia; recurrent toxoplasmosis of brain; HIV wasting syndrome (involuntary weight loss >10% of baseline body weight) with chronic diarrhea or chronic weakness and documented fever for ≥1 month.

Secondary Outcome Measures

Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight
The definition of virologic success included HIV RNA levels <50 c/mL or 400 c/mL at the Week 48 analysis window. .
Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status
The definition of virologic success included HIV RNA levels <50 c/mL or <400 c/mL at the Week 48 analysis.
Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight
Participants who received at least 1 dose of atazanavir (ATV) and had an HIV RNA measurement on ATV powder at did not switch to the capsule formulation before Week 48
Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status
CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight
CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight
Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status
Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir
Criteria for resistance testing= meeting at least 1 of the following: <1 log10 drop from baseline in HIV RNA level by Week 16 and confirmed by a second HIV RNA level; an HIV RNA level >200 copies/mL after Week 24, confirmed by a second HIV RNA level; repeated HIV RNA levels ≥50 copies/mL after Week 48; an HIV RNA level ≥400 copies/mL confirmed by a second HIV RNA level of ≥400 copies/mL at any time in a participant who had previously achieved a plasma HIV RNA level <50 copies/mL; or discontinued due to lack of efficacy. Virologic failure was defined as an incomplete virologic response to therapy or as a viral rebound after the achievement of virologic suppression. The phenotypic resistance to a drug is defined as a fold change (ie, ratio of the 50% inhibitory concentration [IC50] of the clinical isolate to the IC50 of the reference strain) greater than the cut-off for reduced susceptibility.
Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir
Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir
Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir
Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir
Calculated as dose divided by AUC(TAU). AUC(TAU)=area under the concentration-time curve in 1 dosing interval from time 0 to 24 hours post observed dose.
Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir
Calculated as CLT/F divided by body weight

Full Information

First Posted
April 6, 2010
Last Updated
April 26, 2018
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01099579
Brief Title
PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV)
Acronym
PRINCE1
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 HIV Infected Pediatric Patients Greater Than or Equal to 3 Months to Less Than 6 Years. (Pediatric Atazanavir International Clinical Evaluation: the PRINCE I Study)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
October 13, 2010 (Actual)
Primary Completion Date
October 4, 2012 (Actual)
Study Completion Date
September 11, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether atazanavir powder combined with ritonavir is safe and well tolerated and produces appropriate drug exposure in children ≥3 months to <6 years of age.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV, Pediatric

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
82 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atazanavir powder, 150 mg/Ritonavir oral solution, 80 mg
Arm Type
Experimental
Arm Description
Patients weighing 5 to <10 kg received atazanavir (ATV), 150-mg powder dosed in 50-mg packets, and ritonavir (RTV) oral solution, 80 mg. Stage 1: Initial dose was determined by patient's weight on the day of first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage. All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.
Arm Title
Atazanavir powder, 200 mg/Ritonavir oral solution, 80 mg
Arm Type
Experimental
Arm Description
Patients weighing 10 to <15 kg received ATV powder, 200 mg, dosed in 50-mg sachet packets and RTV oral solution, 80 mg. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from the powder to the capsule formulation of ATV. Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.
Arm Title
Atazanavir powder, 250 mg/Ritonavir oral solution, 80 mg
Arm Type
Experimental
Arm Description
Patients weighing 15 to <25 kg received 250 mg of ATV powder dosed in 50-mg sachet packets, with 80 mg of RTV solution. Stage 1: Initial dose was determined by the patient's weight on the day of the first on-treatment study visit (Day 1). ATV dispersible powder was mixed with a small amount of food or beverage (water, milk, chocolate milk, liquid infant formula, applesauce, or yogurt). All of the mixture must have been consumed to obtain the full dose. The RTV oral solution was taken immediately before or after the ATV powder preparation. Stage 2: Patients who reached the age of 6 years or a weight of ≥25kg transitioned from powder to the capsule formulation of ATV. Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.
Intervention Type
Drug
Intervention Name(s)
Atazanavir powder
Other Intervention Name(s)
Reyataz, BMS-232632
Intervention Description
Powder, oral, dosed by weight. Participants who weighed 5 to <10 kg received atazanavir (ATV), 150 mg, and ritonavir (RTV), 80 mg; those who weighed 10 to <15 kg received ATV, 200 mg, and RTV, 80 mg; and those who weighed 15 to <25 kg received ATV, 250 mg, and RTV, 80 mg, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.
Intervention Type
Drug
Intervention Name(s)
Ritonavir oral solution
Other Intervention Name(s)
Norvir
Intervention Description
Oral solution, 80 mg/mL, once per day for 48 weeks or until pediatric indication is locally approved and participant meets requirements to receive appropriate formulation.
Intervention Type
Drug
Intervention Name(s)
Atazanavir capsules
Intervention Description
Capsules, oral, dosed by weight in Stage 2. Patients who reached the age of 6 years or a weight of ≥25 kg transitioned from the powder to the capsule formulation of atazanavir (ATV). Patients who weighed 15 to <20 kg received ATV, 150 mg with RTV, 100 mg; those who weighed 20 to <40 kg received ATV, 200 mg, and RTV, 100 mg; and those who weighed at least 40 kg received ATV, 300 mg with RTV, 100 mg. RTV capsules or tablets were ingested with food immediately before or after ATV intake.
Intervention Type
Drug
Intervention Name(s)
Ritonavir capsules
Intervention Description
Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.
Primary Outcome Measure Information:
Title
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation
Description
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.
Time Frame
From Day 1 to Week 48
Title
Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4
Description
ALT=alanine aminotransferase; SGPT=serum glutamic-pyruvic transaminase; AST=aspartate aminotransferase; SGOT=serum glutamic-oxaloacetic transaminase; ULN=upper limit of normal. Grading by the National Institute of Health Division of AIDs and World Health Organization criteria. Hemoglobin (g/dL): Grade (Gr)1=9.5-11.0; Gr 2=8.0-9.4; Gr 3=6.5-7.9; Gr 4=<6.5. Neutrophils, absolute (/mm^3): Gr 1=>=1000-<1500; Gr 2= >=750-<1000; Gr 3=>=500-<750; Gr 4=<500. ALT/SGPT (*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=>10. AST/SGOT (*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5; Gr 3=5.1-10; Gr 4=>10. Alkaline phosphatase(*ULN): Gr 1=1.25-2.5; Gr 2=2.6-5: Gr 3=5.1-10; Gr 4=>10. Total bilirubin (*ULN): Gr 1=1.1-1; Gr 2=1.6-2.5; Gr 3=2.6-5; Gr 4=>5. Amylase (*ULN): Gr 1=1.10-39; Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=>5.0. Lipase (*ULN): Gr 1=1.10-1.39: Gr 2=1.40-2; Gr 3=2.10-5.0; Gr 4=>5.0. Uric acid (mg/dL): Gr 1=7.5-10.0; Gr 2=10.1-12.0; Gr 3=12.1-15.0; Gr 4=>15.
Time Frame
After Day 1 to Week 48
Title
Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48
Description
Electrocardiogram parameters were measured at baseline for QTC Bazett, QTC Fridericia, and PR interval. The mean change from baseline at week 48 is reported by arm in milliseconds.
Time Frame
From Baseline to Week 48
Title
Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events
Description
CDC Class C events are AIDS-defining events that include recurrent bacterial pneumonia (>=2 episodes in 12 months); candidiasis of the bronchi, trachea, lungs, or esophagus; invasive cervical carcinoma; disseminated or extrapulmonary coccidioidomycosis; extrapulmonary cryptococcosis; chronic intestinal cryptosporidiosis (>1 month); cytomegalovirus disease; HIV-related encephalopathy; herpes simplex: chronic ulcers, or bronchitis, pneumonitis, or esophagitis; disseminated or extrapulmonary histoplasmosis; chronic intestinal isosporiasis; Kaposi sarcoma; immunoblastic or primary brain Burkitt lymphoma; mycobacterium avium complex, kansasii, or tuberculosis; mycobacterium, other species; Pneumocystis carinii pneumonia; progressive multifocal leukoencephalopathy; Salmonella septicemia; recurrent toxoplasmosis of brain; HIV wasting syndrome (involuntary weight loss >10% of baseline body weight) with chronic diarrhea or chronic weakness and documented fever for ≥1 month.
Time Frame
From Day 1 to Week 48
Secondary Outcome Measure Information:
Title
Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight
Description
The definition of virologic success included HIV RNA levels <50 c/mL or 400 c/mL at the Week 48 analysis window. .
Time Frame
At Week 48
Title
Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Description
The definition of virologic success included HIV RNA levels <50 c/mL or <400 c/mL at the Week 48 analysis.
Time Frame
From Day 1 to Week 48
Title
Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight
Description
Participants who received at least 1 dose of atazanavir (ATV) and had an HIV RNA measurement on ATV powder at did not switch to the capsule formulation before Week 48
Time Frame
From Baseline to Week 48
Title
Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Time Frame
From Baseline to Week 48
Title
CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight
Time Frame
From Baseline to Week 48
Title
CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Time Frame
From Baseline to Week 48
Title
Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight
Time Frame
From Baseline to Week 48
Title
Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status
Time Frame
From Baseline to Week 48
Title
Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir
Description
Criteria for resistance testing= meeting at least 1 of the following: <1 log10 drop from baseline in HIV RNA level by Week 16 and confirmed by a second HIV RNA level; an HIV RNA level >200 copies/mL after Week 24, confirmed by a second HIV RNA level; repeated HIV RNA levels ≥50 copies/mL after Week 48; an HIV RNA level ≥400 copies/mL confirmed by a second HIV RNA level of ≥400 copies/mL at any time in a participant who had previously achieved a plasma HIV RNA level <50 copies/mL; or discontinued due to lack of efficacy. Virologic failure was defined as an incomplete virologic response to therapy or as a viral rebound after the achievement of virologic suppression. The phenotypic resistance to a drug is defined as a fold change (ie, ratio of the 50% inhibitory concentration [IC50] of the clinical isolate to the IC50 of the reference strain) greater than the cut-off for reduced susceptibility.
Time Frame
After Day 1 to Week 48
Title
Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir
Time Frame
At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Title
Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir
Time Frame
At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Title
Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir
Time Frame
At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Title
Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir
Description
Calculated as dose divided by AUC(TAU). AUC(TAU)=area under the concentration-time curve in 1 dosing interval from time 0 to 24 hours post observed dose.
Time Frame
At Week 2
Title
Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir
Description
Calculated as CLT/F divided by body weight
Time Frame
At Week 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
66 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Confirmed human immunodeficiency virus (HIV)-1 infection diagnosed by a positive virologic test result on 2 separate occasions by: HIV DNA polymerase chain reaction HIV RNA with values ≥1,000 copies/mL Positive HIV enzyme-linked immunosorbent assay at ≥18 months of age, with confirmatory Western blot or indirect immunoflourescence antibody Infants and children of either sex, aged ≥3 months to <5 years and 6 months at time of first treatment, and weight >5 to <25 kg with any screening baseline plasma viral load Screening plasma viral load ≥1,000 copies/mL by Roche Amplicor® HIV RNA Assay Documented genotypic and phenotypic sensitivity at screening to ATV (fold change in susceptibility <2.2) and to at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) approved in the infant's country Genotypic sensitivity at screening to atazanavir (ATV) and at least 2 NRTIs Antiretroviral (ARV) treatment-naive or ARV treatment-experienced. Treatment-experienced participants are defined by previous exposure to ARVs through either prior treatment for HIV infection or through postnatal treatment with ≥1 ARV for the prevention of mother to child transmission. For the purposes of this study, participants exposed to ARVs in utero or intrapartum may be included in the study but will be considered treatment naive. ATV-naive participants must have genotypic sensitivity at screening to ATV (fold change in susceptibility <2.2) and to both components of the local NRTI backbone. The NRTIs must have been approved for pediatric use at the local country level. Key Exclusion Criteria: Experienced participants who received ATV or ATV/ritonavir (RTV) at any time prior to study enrollment or with a history of 2 or more protease inhibitor failures ARV-naïve or -experienced HIV-1 infected patients with contraindication to study medications syncope Family history of QTc interval syndrome, Brugada syndrome, right ventricular dysplasia, or a corrected QTc interval at screening of >440 ms One of the following cardiac rhythm abnormalities documented on screening electrocardiogram: 1st degree atrioventricular (AV) block as defined by protocol, type I 2nd degree AV block while awake, type II 2nd degree AV block at any time, complete AV block at any time, or age-adjusted heart rate <2nd percentile) History of pancreatitis, peripheral neuropathy, malignancy that requires systemic therapy, or any medical condition which, in the opinion of the investigator, added undue risk to trial participation Malabsorption syndrome Presence of a newly diagnosed HIV-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment Weight <5 or ≥25 kg at date of first dose (Day 1). >Grade 2 aspartate transaminase or alanine transaminase abnormalities Hypersensitivity to any component of the study medication formulations (ATV/RTV, or a locally prescribed NRTI with a pediatric indication) Infants and children of either gender <3 months or ≥5 years and 6 months at the time of first treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Sao Paolo
State/Province
SAO Paulo
ZIP/Postal Code
01246-900
Country
Brazil
Facility Name
Local Institution
City
Santiago
State/Province
Metropolitana
ZIP/Postal Code
8380418
Country
Chile
Facility Name
Local Institution
City
Santiago
State/Province
Metropolitana
Country
Chile
Facility Name
Local Institution
City
Df
State/Province
Distrito Federal
ZIP/Postal Code
06720
Country
Mexico
Facility Name
Local Institution
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44160
Country
Mexico
Facility Name
Local Institution
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44280
Country
Mexico
Facility Name
Local Institution
City
Merida
State/Province
Yucatan
ZIP/Postal Code
97000
Country
Mexico
Facility Name
Local Institution
City
Oaxaca
ZIP/Postal Code
71256
Country
Mexico
Facility Name
Local Institution
City
Puebla
ZIP/Postal Code
72000
Country
Mexico
Facility Name
Local Institution
City
Lima
ZIP/Postal Code
1
Country
Peru
Facility Name
Local Institution
City
Lima
Country
Peru
Facility Name
Local Institution
City
Bloemfontein
State/Province
FREE State
ZIP/Postal Code
9301
Country
South Africa
Facility Name
Local Institution
City
Coronationville
State/Province
Gauteng
ZIP/Postal Code
2092
Country
South Africa
Facility Name
Local Institution
City
Soweto
State/Province
Gauteng
ZIP/Postal Code
2001
Country
South Africa
Facility Name
Local Institution
City
Congella
State/Province
KWA ZULU Natal
ZIP/Postal Code
4013
Country
South Africa
Facility Name
Local Institution
City
Cape Town
State/Province
Western CAPE
ZIP/Postal Code
7505
Country
South Africa
Facility Name
Local Institution
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Local Institution
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand

12. IPD Sharing Statement

Links:
URL
http://bms.com/studyconnect/Pages/home.aspx
Description
BMS Clinical Trial Patient Recruiting

Learn more about this trial

PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV)

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