HIV InfectionsPhase 3PRINCE1NCT01099579
PRINCE: Study of Atazanavir (ATV)/Ritonavir (RTV)
A Phase 3 study testing Atazanavir powder, Ritonavir oral solution and Atazanavir capsules in people with HIV Infections, run by Bristol-Myers Squibb at 18 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 66 months
- Conditions the study is for
- HIV Infections
- What is being tested?
- Atazanavir powder, Ritonavir oral solution and Atazanavir capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 18 sitesin 6 countries
- Study dates
- 13 Oct 2010to 11 Sep 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 66 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
18 sites in 6 countries.
18 sites in 6 countries
Mexico6 sites
Local Institution
Df, Mexico City, 06720
Local Institution
Guadalajara, Jalisco, 44160
Local Institution
Guadalajara, Jalisco, 44280
Local Institution
Mérida, Yucatán, 97000
Local Institution
Oaxaca City, 71256
Local Institution
Puebla City, 72000
South Africa5 sites
Local Institution
Bloemfontein, Free State, 9301
Local Institution
Cape Town, Western Cape, 7505
Local Institution
Coronationville, Gauteng, 2092
Local Institution
KwaKhangela, KwaZulu-Natal, 4013
Local Institution
Soweto, Gauteng, 2001
Chile2 sites
Local Institution
Santiago, Santiago Metropolitan, 8380418
Local Institution
Santiago, Santiago Metropolitan
Thailand2 sites
Local Institution
Bangkok, 10330
Local Institution
Bangkok, 10700
About this study
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)
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.
- Conditions
- HIV Infections
- Being tested
- Atazanavir powder, Ritonavir oral solution, Atazanavir capsules, Ritonavir capsules
- Keywords
- HIV, Pediatric
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atazanavir powderDrug
Also called Reyataz, BMS-232632
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.
Ritonavir oral solutionDrug
Also called Norvir
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.
Atazanavir capsulesDrug
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.
Ritonavir capsulesDrug
Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.
| Study group | Role | What they receive |
|---|---|---|
| Atazanavir powder, 150 mg/Ritonavir oral solution, 80 mg | Experimental | 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. Receives: Drug: Atazanavir powder; Drug: Ritonavir oral solution; Drug: Atazanavir capsules; Drug: Ritonavir capsules |
| Atazanavir powder, 200 mg/Ritonavir oral solution, 80 mg | Experimental | 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. Receives: Drug: Atazanavir powder; Drug: Ritonavir oral solution; Drug: Atazanavir capsules; Drug: Ritonavir capsules |
| Atazanavir powder, 250 mg/Ritonavir oral solution, 80 mg | Experimental | 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. Receives: Drug: Atazanavir powder; Drug: Ritonavir oral solution; Drug: Atazanavir capsules; Drug: Ritonavir capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From Day 1 to Week 48
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.
Measured: After Day 1 to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Day 1 to Week 48
Secondary outcomes (14)
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. .
Measured: At Week 48
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.
Measured: From Day 1 to Week 48
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
Measured: From Baseline to Week 48
Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Measured: From Baseline to Week 48
CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight
Measured: From Baseline to Week 48
CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Measured: From Baseline to Week 48
Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight
Measured: From Baseline to Week 48
Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status
Measured: From Baseline to Week 48
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.
Measured: After Day 1 to Week 48
Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Atazanavir and Ritonavir
Measured: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Area Under the Concentration Curve (in 1 Dosing Interval From Time 0 to 24 Hours Post Observed Dose) (AUC[TAU])of Atazanavir and Ritonavir
Measured: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
Time to Maximum Observed Concentration (Tmax) of Atazanavir and Ritonavir
Measured: At Week 2 at Hour 0 predose and at Hours 1.5, 2.5, 4, 6, 8, 12, and 24 postdose
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.
Measured: At Week 2
Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir
Calculated as CLT/F divided by body weight
Measured: At Week 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2010 (estimated)
- Study start13 Oct 2010
- Primary completion4 Oct 2012
- Study completion11 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01099579
- Sponsor's protocol ID
- AI424-397
- Other IDs
- 2009-016361-28, 2009
- Acronym
- PRINCE1
- Status last verified
- Apr 2018
- First submitted
- 6 Apr 2010
- Last updated
- 24 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01099579
- Acronym / sponsor ID
- PRINCE1 / AI424-397
- Conditions
- HIV Infections
- Keywords
- HIV, Pediatric
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 13 Oct 2010 (actual)
- Primary completion
- 4 Oct 2012 (actual)
- Study completion
- 11 Sep 2017 (actual)
- First posted
- 7 Apr 2010 (estimated)
- Results
- Posted 6 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Atazanavir powder, 150 mg/Ritonavir oral solution, 80 mg | Experimental | Drug: Atazanavir powder, Drug: Ritonavir oral solution, Drug: Atazanavir capsules, Drug: Ritonavir capsulesPatients 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. |
| Atazanavir powder, 200 mg/Ritonavir oral solution, 80 mg | Experimental | Drug: Atazanavir powder, Drug: Ritonavir oral solution, Drug: Atazanavir capsules, Drug: Ritonavir capsulesPatients 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. |
| Atazanavir powder, 250 mg/Ritonavir oral solution, 80 mg | Experimental | Drug: Atazanavir powder, Drug: Ritonavir oral solution, Drug: Atazanavir capsules, Drug: Ritonavir capsulesPatients 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. |
Who may qualify
- Ages
- 3 to 66 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Confirmed human immunodeficiency virus (HIV)-1 infection diagnosed by a positive virologic test result on 2 separate occasions by:
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atazanavir powderAlso: Reyataz, BMS-232632Powder, 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. | Drug | 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 |
| Ritonavir oral solutionAlso: NorvirOral 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. | Drug | 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 |
| Atazanavir capsulesCapsules, 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. | Drug | 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 |
| Ritonavir capsulesOral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight. | Drug | 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 |
Primary outcome
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation
Time frame: From Day 1 to Week 48
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
Time frame: After Day 1 to Week 48
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
Time frame: From Baseline to 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
Time frame: From Day 1 to Week 48
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.
14 secondary outcomes
Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight
Time frame: At Week 48
Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Time frame: From Day 1 to Week 48
Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight
Time frame: From Baseline to Week 48
Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Time frame: From Baseline to Week 48
CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight
Time frame: From Baseline to Week 48
CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status
Time frame: From Baseline to Week 48
Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight
Time frame: From Baseline to Week 48
Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status
Time frame: From Baseline to Week 48
Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir
Time frame: After Day 1 to Week 48
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
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
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
Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir
Time frame: At Week 2
Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir
Time frame: At Week 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
18 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atazanavir powder, Ritonavir oral solution and Atazanavir capsules in people with HIV Infections, run by Bristol-Myers Squibb at 18 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Mexico, South Africa, Chile, Peru, Thailand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation (time frame: From Day 1 to Week 48). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2018.