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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01099579
First received: April 6, 2010
Last updated: August 19, 2014
Last verified: August 2014
Results First Received: November 14, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Atazanavir powder
Drug: Ritonavir oral solution
Drug: Atazanavir capsules
Drug: Ritonavir capsules

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 82 pediatric patients were enrolled, and 56 received treatment. Reasons for not receiving treatment treated were: no longer met study criteria (23 patients), other reason (2 patients), and withdrew consent (1 patient).

Reporting Groups
  Description
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 sachet packets, and ritonavir (RTV) oral solution, 80 mg. Stage 1: Initial dose was determined by 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). If water was used, mixture must have been taken with food. The entire contents of the mixture must have been consumed to obtain the full dose. The ritonavir 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 25 kg were transitioned to the capsule formulation of ATV. Those who weighed 15 to <20 kg received ATV, 150 mg, with RTV, 100 mg; those who weighed 20 to <40 mg received ATV, 200, with RTV, 100 mg; and those who weighed at least 40 mg received ATV, 300 mg, with RTV, 100 mg.
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). If water was used, mixture must have been taken with food. 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 25 kg were transitioned to the capsule formulation of ATV. Those who weighed 15 to <20 kg received ATV, 150 mg, with RTV, 100 mg; those who weighed 20 to <40 mg received ATV, 200, with RTV, 100 mg; and those who weighed at least 40 mg received ATV, 300 mg, with RTV, 100 mg.
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). If water was used, mixture must have been taken with food. The entire contents of the mixture must have been consumed to obtain the full dose. The ritonavir 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 25 kg were transitioned to the capsule formulation of ATV. Those who weighed 15 to <20 kg received ATV, 150 mg, with RTV, 100 mg; those who weighed 20 to <40 mg received ATV, 200, with RTV, 100 mg; and those who weighed at least 40 mg received ATV, 300 mg, with RTV, 100 mg.

Participant Flow for 2 periods

Period 1:   Stage 1 (ATV Powder Formulation)
    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  
STARTED     21     19     16  
COMPLETED     17 [1]   14 [1]   15 [1]
NOT COMPLETED     4     5     1  
Adverse Event                 4                 1                 0  
Withdrawal by Subject                 0                 0                 1  
Lack of Efficacy                 0                 2                 0  
Poor compliance/noncompliance                 0                 2                 0  
[1] Completed Stage 1

Period 2:   Stage 2 (ATV Capsules )
    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  
STARTED     16     14     15  
COMPLETED     0     0     0  
NOT COMPLETED     16     14     15  
No longer met study criteria                 2                 0                 0  
Lost to Follow-up                 0                 1                 0  
Ongoing treatment                 14                 13                 15  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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 sachet packets, and ritonavir (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). If water was used, mixture must have been taken with food. The entire contents of the mixture must have been consumed to obtain the full dose. The ritonavir 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 25 kg were transitioned to the capsule formulation of ATV. RTV capsules or tablets were ingested with food immediately before or after ATV intake.
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). If water was used, mixture must have been taken with food. 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 25 kg were transitioned to the capsule formulation of ATV. Those who weighed 15 to 20 kg received ATV, 150 mg, with RTV, 100 mg, and those who weighed 20 to 40 mg received ATV, 200 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 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). If water was used, mixture must have been taken with food. The entire contents of the mixture must have been consumed to obtain the full dose. The ritonavir 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 25 kg were transitioned to the capsule formulation of ATV. Those who weighed 20 to 40 mg received ATV, 200 mg, with 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.
Total Total of all reporting groups

Baseline Measures
    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     Total  
Number of Participants  
[units: participants]
  21     19     16     56  
Age  
[units: Months]
Mean ± Standard Deviation
  7.3  ± 4.05     35.4  ± 11.63     52.1  ± 10.49     29.6  ± 20.72  
Gender  
[units: participants]
       
Female     10     12     6     28  
Male     11     7     10     28  
Race/Ethnicity, Customized  
[units: Participants]
       
Not Hispanic or Latino     0     0     1     1  
Not reported     21     19     15     55  
Race/Ethnicity, Customized  
[units: participants]
       
White     2     3     6     11  
Black/African American     13     12     7     32  
Asian     0     1     0     1  
Other     6     3     3     12  
Country  
[units: Participants]
       
Chile     1     2     3     6  
Mexico     2     3     4     9  
Peru     1     0     1     2  
South Africa     17     13     8     38  
Thailand     0     1     0     1  
HIV RNA  
[units: Log10┬ác/mL]
Mean ± Standard Deviation
  4.77  ± 0.602     4.83  ± 0.268     4.18  ± 0.727     4.62  ± 0.617  
HIV RNA Categories (n=3, 2, 9) [1]
[units: c/mL]
       
<30,000     3     2     9     14  
30,000 to 100,000     0     7     3     10  
>100,000     18     10     4     32  
CD4 Count (n=16, 13, 10) [1]
[units: Cells/mm^3]
Mean ± Standard Deviation
  1594.1  ± 897.19     1107.4  ± 643.25     661.1  ± 302.60     1192.6  ± 784.08  
CD4 Percent (n=16, 14, 11) [1]
[units: Percentage]
Mean ± Standard Deviation
  25.4  ± 12.11     22.0  ± 9.35     27.5  ± 9.85     24.8  ± 10.61  
CD4 Percent Categories  
[units: Participants]
       
<15     2     2     1     5  
15 to <25     7     6     4     17  
>=25     7     6     6     19  
Not reported     5     5     5     15  
Prior Antiretroviral (ARV) Treatment Use [2]
[units: Participants]
       
ARV naive     13     12     9     34  
ARV experienced     8     7     7     22  
[1] n=number of evaluable participants
[2] ATV naive is defined as without prior exposure to ARV treatment; ARV experienced is defined as previous exposure to ARV drugs through prior treatment for HIV infection or through postnatal treatment with ≥1 ARVs for the prevention of mother-to-child-transmission in accordance with multiple international guidelines. Patients exposed to ARVs in utero or intrapartum were permitted in the study but were considered treatment naive.



  Outcome Measures
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1.  Primary:   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 ]

2.  Primary:   Number of Participants With Laboratory Test Results With Worst Toxicity of Grade 3-4   [ Time Frame: From Day 1 to Week 48 ]

3.  Primary:   Electrocardiogram Changes From Baseline in PR Interval, QTC Bazett, and QTC Fridericia at Week 48   [ Time Frame: From Baseline to Week 48 ]

4.  Primary:   Number of Participants With Centers for Disease Control (CDC) Class C AIDS Events   [ Time Frame: From Day 1 to Week 48 ]

5.  Secondary:   Percentage of Participants With HIV RNA Levels <50 c/mL and <400 c/mL at Week 48 by Treatment/Weight   [ Time Frame: From Day 1 to Week 48 ]

6.  Secondary:   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 ]

7.  Secondary:   Mean Change From Baseline in HIV RNA Levels at Week 48 by Treatment/Weight   [ Time Frame: From Baseline to Week 48 ]

8.  Secondary:   Mean Change From Baseline in HIV RNA Levels at Week 48 by Prior Antiretroviral (ARV) Treatment Status   [ Time Frame: From Baseline to Week 48 ]

9.  Secondary:   CD4 Cell Count Changes From Baseline at Week 48 by Treatment/Weight   [ Time Frame: From Baseline to Week 48 ]

10.  Secondary:   CD4 Cell Count Changes From Baseline at Week 48 by Prior Antiretroviral (ARV) Treatment Status   [ Time Frame: From Baseline to Week 48 ]

11.  Secondary:   Mean CD4 Percent Changes From Baseline at Week 48 by Treatment/Weight   [ Time Frame: From Baseline to Week 48 ]

12.  Secondary:   Mean CD4 Percent Changes From Baseline at Week 48 by Antiretroviral (ARV) Treatment Status   [ Time Frame: From Baseline to Week 48 ]

13.  Secondary:   Number of Participants Who Acquired Phenotypic Resistance to Atazanavir or Atazanovir/Ritonavir   [ Time Frame: From Day 1 to Week 48 ]

14.  Secondary:   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 ]

15.  Secondary:   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 ]

16.  Secondary:   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 ]

17.  Secondary:   Apparent Total Body Clearance (CLT/F) of Atazanavir and Ritonavir   [ Time Frame: At Week 2 ]

18.  Secondary:   Apparent Total Body Clearance Per Body Weight (CLT/F) Per Kilogram of Atazanavir and Ritonavir   [ Time Frame: At Week 2 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01099579     History of Changes
Other Study ID Numbers: AI424-397, 2009-016361-28
Study First Received: April 6, 2010
Results First Received: November 14, 2013
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration