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

Browse trials for

• HIV Infections 4,340

Keywords

• HIV, Pediatric

HIV Infections

4,340 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 82 is close to the median of 83 across 3,312 interventional studies indexed under HIV Infections.

Lead sponsor

Bristol-Myers Squibb is the lead sponsor of 1,562 studies on the registry; 118 are open to participants now.

Of its 435 completed or terminated interventional studies of FDA-regulated products, 227 (52%) have results posted.

Eligibility criteria

Study arms

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

  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.

  Drug: Atazanavir powder · Drug: Ritonavir oral solution · Drug: Atazanavir capsules · Drug: Ritonavir capsules

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

  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.

  Drug: Atazanavir powder · Drug: Ritonavir oral solution · Drug: Atazanavir capsules · Drug: Ritonavir capsules

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

  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.

  Drug: Atazanavir powder · Drug: Ritonavir oral solution · Drug: Atazanavir capsules · Drug: Ritonavir capsules

Interventions

• DrugAtazanavir powder

  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.

  Also known as: Reyataz, BMS-232632

• DrugRitonavir oral solution

  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.

  Also known as: Norvir

• DrugAtazanavir capsules

  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.

• DrugRitonavir capsules

  Oral, capsules, 100 mg, administered in Stage 2 with atazanavir capsules, dosed by weight.

Primary outcomes

1. 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.

   Time frame: From Day 1 to Week 48

2. 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.

   Time frame: After Day 1 to Week 48

3. 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.

   Time frame: From Baseline to Week 48

4. 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.

   Time frame: From Day 1 to Week 48

Secondary outcomes

1. 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. .

   Time frame: At Week 48

2. 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.

   Time frame: From Day 1 to Week 48

3. 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

   Time frame: From Baseline to Week 48

4. Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status

   Time frame: From Baseline to Week 48

5. CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight

   Time frame: From Baseline to Week 48

6. CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status

   Time frame: From Baseline to Week 48

7. Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight

   Time frame: From Baseline to Week 48

8. Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status

   Time frame: From Baseline to Week 48

9. 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.

   Time frame: After Day 1 to Week 48

10. 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

11. 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

12. 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

13. 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.

    Time frame: At Week 2

14. Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir

    Calculated as CLT/F divided by body weight

    Time frame: At Week 2

Baseline characteristics

3 further baseline measures are reported on the registry.