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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01335698
First received: April 13, 2011
Last updated: January 8, 2016
Last verified: October 2015
Results First Received: October 26, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV
Interventions: Drug: Atazanavir Sulphate
Drug: Ritonavir

  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
Of 160 participants enrolled, 99 received treatment.

Reporting Groups
  Description
Atazanavir, 150 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg) Stage 1: HIV-infected pediatric patients weighing 5 to <10 kg at baseline received atazanir powder formulation, 150 mg, with ritonavir oral solution, 80 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg) Stage 1: HIV-infected pediatric patients weighing 5 to <10 kg at baseline received atazanir powder formulation, 150 mg, with ritonavir oral solution, 80 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 10 to <15 kg) Stage 1: HIV-infected pediatric patients weighing 10 to <15 kg at baseline received atazanir powder formulation, 200 mg, with ritozinavir oral solution, 80 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 250 mg + Ritonavir, 80 mg (Weight: 15 to <25 kg) Stage 1: HIV-infected pediatric patients weighing 15 to <25 kg at baseline received atazanir powder formulation, 250 mg, with ritozinavir oral solution, 80 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: 25 to <35 kg) Stage 1: HIV-infected pediatric patients weighing 10 to <15 kg at baseline received atazanir powder formulation, 300 mg, with ritozinavir capsule/tablets, 100 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.

Participant Flow for 2 periods

Period 1:   Treatment Stage 1
    Atazanavir, 150 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg)     Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg)     Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 10 to <15 kg)     Atazanavir, 250 mg + Ritonavir, 80 mg (Weight: 15 to <25 kg)     Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: 25 to <35 kg)  
STARTED     23     12     21     35     8  
COMPLETED     15     4     16     26     6  
NOT COMPLETED     8     8     5     9     2  
Lack of Efficacy                 3                 1                 3                 3                 1  
Adverse Event                 1                 2                 2                 1                 1  
Withdrawal by Subject                 1                 2                 0                 1                 0  
Lost to Follow-up                 1                 1                 0                 0                 0  
Poor compliance/noncompliance                 0                 1                 0                 2                 0  
No longer meets study criteria                 1                 1                 0                 1                 0  
Not specified                 1                 0                 0                 1                 0  

Period 2:   Treatment Stage 2
    Atazanavir, 150 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg)     Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg)     Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 10 to <15 kg)     Atazanavir, 250 mg + Ritonavir, 80 mg (Weight: 15 to <25 kg)     Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: 25 to <35 kg)  
STARTED     15     4     16     26     6  
COMPLETED     0     0     0     2     0  
NOT COMPLETED     15     4     16     24     6  
Lack of Efficacy                 2                 1                 3                 1                 0  
Adverse Event                 0                 0                 0                 1                 0  
Withdrawal by Subject                 1                 0                 0                 0                 0  
Poor compliance/noncompliance                 1                 0                 0                 3                 0  
Continuing treatment                 11                 3                 13                 19                 6  



  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.
All participants who received at least 1 dose of study drug

Reporting Groups
  Description
Atazanavir, 150 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg) Stage 1: HIV-infected pediatric patients weighing 5 to <10 kg at baseline received atazanir powder formulation, 150 mg, with ritonavir oral solution, 80 mg, for 24 to 48 weeks.Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg) Stage 1: HIV-infected pediatric patients weighing 5 to <10 kg at baseline received atazanir powder formulation, 200 mg, with ritonavir oral solution, 80 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 10 to <15 kg) Stage 1: HIV-infected pediatric patients weighing 10 to <15 kg at baseline received atazanir powder formulation, 200 mg, with ritozinavir oral solution, 80 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 250 mg + Ritonavir, 80 mg (Weight: 15 to <25 kg) Stage 1: HIV-infected pediatric patients weighing 15 to <25 kg at baseline received atazanir powder formulation, 250 mg, with ritozinavir oral solution, 80 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: 25 to <35 kg) Stage 1: HIV-infected pediatric patients weighing 10 to <15 kg at baseline received atazanir powder formulation, 300 mg, with ritozinavir capsule/tablets, 100 mg, for 24 to 48 weeks. Patients entering Stage 2 continued Stage 1 treatment but those aged 12 years or older or weighing at least 35 kg transitioned to capsules. Treatment continued until the patient reached 18 years of age or pediatric indication is locally approved and patient meets requirements to receive appropriate formulation.
Total Total of all reporting groups

Baseline Measures
    Atazanavir, 150 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg)     Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 5 to <10 kg)     Atazanavir, 200 mg + Ritonavir, 80 mg (Weight: 10 to <15 kg)     Atazanavir, 250 mg + Ritonavir, 80 mg (Weight: 15 to <25 kg)     Atazanavir, 300 mg + Ritonavir, 100 mg (Weight: 25 to <35 kg)     Total  
Number of Participants  
[units: participants]
  23     12     21     35     8     99  
Age  
[units: Months]
Mean (Standard Deviation)
  8.4  (6.42)     10.5  (9.21)     37.4  (12.44)     67.2  (16.70)     93.4  (15.53)     42.5  (31.58)  
Age  
[units: Months]
Median (Full Range)
  5.0  
  (3.0 to 25.0)  
  5.5  
  (3.0 to 30.0)  
  36.0  
  (15.0 to 69.0)  
  68.0  
  (35.0 to 115.0)  
  86.5  
  (79.0 to 120.0)  
  41.0  
  (3.0 to 120.0)  
Gender  
[units: participants]
           
Female     12     6     12     18     3     51  
Male     11     6     9     17     5     48  
Ethnicity (NIH/OMB)  
[units: Participants]
           
Hispanic or Latino     0     1     2     1     0     4  
Not Hispanic or Latino     1     1     1     1     0     4  
Unknown or Not Reported     22     10     18     33     8     91  
Race/Ethnicity, Customized  
[units: Participants]
           
White     2     2     12     13     3     32  
Black/African American     19     6     7     20     5     57  
Other     2     4     2     2     0     10  
Region of Enrollment  
[units: Participants]
           
North America     2     1     9     4     2     18  
South America     1     1     1     4     1     8  
Africa     20     10     8     21     5     64  
Europe     0     0     3     6     0     9  
Country  
[units: Participants]
           
Argentina     0     1     1     2     0     4  
Brazil     0     0     0     1     0     1  
Chile     1     0     0     1     1     3  
Mexico     1     1     7     4     2     15  
Poland     0     0     1     0     0     1  
Romania     0     0     0     1     0     1  
Russia     0     0     1     3     0     4  
South Africa     20     10     8     21     5     64  
Spain     0     0     1     2     0     3  
United States     1     0     2     0     0     3  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Who Died and With Adverse Events (AEs) Leading to Discontinuation, Hyperbilirubinemia, Jaundice, First-degree Arterioventricular Block, Tachycardia, and Rash   [ Time Frame: Day 1 of treatment through Week 48 ]

2.  Primary:   Number of Participants With A Center of Disease Control and Prevention (CDC) Class C AIDS Event   [ Time Frame: Day 1 of treatment through Week 48 ]

3.  Primary:   Number of Participants With Laboratory Test Results Meeting the Criteria for Grade 3-4 Abnormality   [ Time Frame: Day 1 of treatment through Week 48 ]

4.  Secondary:   Number of Participants With HIV RNA <50 Copies/mL and <400 Copies/mL in the Week 24 Atazanavir Powder Cohort and the Eligible Week 48 Atazanavir Powder Cohort   [ Time Frame: Day 1 of treatment to Weeks 24 and 48 ]

5.  Secondary:   HIV RNA Changes From Baseline   [ Time Frame: Baseline to Weeks 24 and 48 ]

6.  Secondary:   CD4 Percent Changes From Baseline   [ Time Frame: Baseline to Weeks 24 and 48 ]

7.  Secondary:   CD4 Cell Count Changes From Baseline   [ Time Frame: Baseline to Weeks 24 and 48 ]

8.  Secondary:   Number of Participants With Emergent Genotypic Substitutions   [ Time Frame: Baseline through Week 48 ]


  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



Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01335698     History of Changes
Other Study ID Numbers: AI424-451
2010-024537-23 ( EudraCT Number )
Study First Received: April 13, 2011
Results First Received: October 26, 2015
Last Updated: January 8, 2016
Health Authority: United States: Food and Drug Administration
South Africa: Medicines Control Council
Romania: National Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
Brazil: Ethics Committee
Brazil: Ministry of Health
Brazil: National Committee of Ethics in Research
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Chile: Instituto de Salud Pública de Chile
Mexico: Ethics Committee
Mexico: Ministry of Health
Mexico: Secretaria de Salud
Russia: Ethics Committee
Russia: FSI Scientific Center of Expertise of Medical Application
Russia: Ministry of Health of the Russian Federation
Poland: Ethics Committee
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Poland: The Central Register of Clinical Trials
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica