Atazanavir Used in Combination With Other Anti-HIV Drugs in HIV-Infected Infants, Children, and Adolescents

This study has been completed.
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00006604
First received: December 6, 2000
Last updated: March 7, 2016
Last verified: March 2016
Results First Received: January 29, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: ATV
Drug: Ritonavir

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Date of First Enrollment: 16 November 2000; Date of Last Enrollment: 22 December 2009

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Group 1: ATV Dose: Powder (310mg/m^2) Group 1 enrolled participants between 91 days of age and 2 years of age. They received ATV (powder) and two NRTIs.
Group 1: ATV Dose: Powder (620mg/m^2) Group 1 enrolled participants between 91 days of age and 2 years of age. They received ATV (powder) and two NRTIs.
Group 2: ATV Powder (310mg/m^2) Group 2 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (powder) and two NRTIs.
Group 2: ATV Powder (620mg/m^2) Group 2 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (powder) and two NRTIs.
Group 3: ATV Capsule (310mg/m^2) Group 3 enrolled participants between 2 years and 1 day of age and 13 years of age. They will received ATV (capsule) and two NRTIs.
Group 3: ATV Capsule (415mg/m^2) Group 3 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (capsule) and two NRTIs.
Group 3: ATV Capsule (520mg/m^2)

Group 3 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (capsule) and two NRTIs.

Note: This is the final recommended dose for this group.

Group 4: ATV Capsule (310mg/m^2) Group 4 enrolled participants between 13 years and 1 day of age and 21 years of age. They received ATV (capsule) and two NRTIs.
Group 4: ATV Capsule (520mg/m^2) Group 4 enrolled participants between 13 years and 1 day of age and 21 years of age. They received ATV (capsule) and two NRTIs.
Group 4: ATV Capsule (620mg/m^2)

Group 4 enrolled participants between 13 years and 1 day of age and 21 years of age. They received ATV (capsule) and two NRTIs.

Note: This is the final recommended dose for this group.

Group 5: ATV Powder (310mg/m^2) + RTV

Group 5 enrolled participants between 91 days of age and 2 years of age. They received ATV (powder), ritonavir, and two NRTIs.

Note: This is the final recommended dose for this group.

Group 5a: ATV Powder (310mg/m^2) + RTV

Group 5a enrolled participants between 91 days of age and 180 days of age. They received ATV (powder), ritonavir, and two NRTIs.

Note: This is the final recommended dose for this group.

Group 6: ATV Powder (310mg/m^2) + RTV

Group 6 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (powder), ritonavir, and two NRTIs.

Note: This is the final recommended dose for this group.

Group 7: ATV Capsule (310mg/m^2) + RTV Group 7 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (capsule), ritonavir, and two NRTIs.
Group 7: ATV Capsule (205mg/m^2) + RTV

Group 7 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (capsule), ritonavir, and two NRTIs.

Note: This is the final recommended dose for this group.

Group 8: ATV Capsule (310mg/m^2) + RTV Group 8 enrolled participants between 13 years and 1 day of age and 21 years of age. They received ATV (capsule), ritonavir, and two NRTIs.
Group 8: ATV Capsule (205mg/m^2) + RTV

Group 8 enrolled participants between 13 years and 1 day of age and 21 years of age. They received ATV (capsule), ritonavir, and two NRTIs.

Note: This is the final recommended dose for this group.


Participant Flow:   Overall Study
    Group 1: ATV Dose: Powder (310mg/m^2)     Group 1: ATV Dose: Powder (620mg/m^2)     Group 2: ATV Powder (310mg/m^2)     Group 2: ATV Powder (620mg/m^2)     Group 3: ATV Capsule (310mg/m^2)     Group 3: ATV Capsule (415mg/m^2)     Group 3: ATV Capsule (520mg/m^2)     Group 4: ATV Capsule (310mg/m^2)     Group 4: ATV Capsule (520mg/m^2)     Group 4: ATV Capsule (620mg/m^2)     Group 5: ATV Powder (310mg/m^2) + RTV     Group 5a: ATV Powder (310mg/m^2) + RTV     Group 6: ATV Powder (310mg/m^2) + RTV     Group 7: ATV Capsule (310mg/m^2) + RTV     Group 7: ATV Capsule (205mg/m^2) + RTV     Group 8: ATV Capsule (310mg/m^2) + RTV     Group 8: ATV Capsule (205mg/m^2) + RTV  
STARTED     6     2     5     6     5     5     21     5     5     25     21     12     26     6     24     6     15  
COMPLETED     4     2     1     1     3     2     12     2     4     6     13     6     22     0     14     1     6  
NOT COMPLETED     2     0     4     5     2     3     9     3     1     19     8     6     4     6     10     5     9  
Met study objective - no further FU                 1                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 1                 0  
Randomization entry error-no RX, no FU                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0                 0  
Death                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 1                 1                 0                 0                 0                 0                 0  
Severe debilitation, unable to continue                 0                 0                 0                 0                 0                 0                 3                 0                 0                 5                 0                 2                 1                 0                 2                 0                 0  
Subj/Parent not able to get to clinic                 0                 0                 0                 1                 1                 0                 1                 0                 0                 1                 2                 1                 1                 1                 3                 0                 0  
Site closing                 0                 0                 1                 1                 0                 0                 0                 1                 0                 0                 0                 1                 1                 1                 0                 0                 1  
Withdrawal by Subject                 1                 0                 2                 0                 1                 2                 2                 0                 1                 3                 2                 0                 1                 2                 1                 0                 1  
Subj/parent not willing to adhere to req                 0                 0                 1                 3                 0                 0                 3                 1                 0                 6                 3                 0                 0                 2                 3                 3                 4  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 0                 1                 0                 2                 0                 0                 0                 0                 0                 1                 3  
Other Reason                 0                 0                 0                 0                 0                 1                 0                 0                 0                 1                 0                 0                 0                 0                 0                 0                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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.

Participants accrued and treated at the dose ultimately selected for their groups.

NOTE: (1) Final Dose not established for Grps 1, 2; (2) Grp 5a started with n=12, but (1) participant inadvertently enrolled,never received ATV, final n=11; (3) Grp 8 started with n=15, but (1) participant inadvertently enrolled, never received ATV, final n=14.


Reporting Groups
  Description
Step I: Group 3 (ATV Final Dose: 520mg/m^2 Capsule)

Group 3 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (capsule) and two NRTIs.

ATV: Participants received varying doses of ATV, depending on their age and weight. The medication was administered as 50 mg, 100 mg, or 200 mg capsules or a powder formulation, depending on which study arm participants were in.

ATV Final Recommended Dose: 520mg/m^2

Step I: Group 4 (ATV Final Dose: 620mg/m^2 Capsule)

Group 4 enrolled participants between 13 years and 1 day of age and 21 years of age. They received ATV (capsule) and two NRTIs.

ATV: Participants received varying doses of ATV, depending on their age and weight. The medication was administered as 50 mg, 100 mg, or 200 mg capsules or a powder formulation, depending on which study arm participants were in.

ATV Final Recommended Dose: 620mg/m^2

Step I: Group 5 (ATV Final Dose: 310mg/m^2 Powder + RTV)

Group 5 enrolled participants between 91 days of age and 2 years of age. They received ATV (powder), ritonavir, and two NRTIs.

ATV: Participants received varying doses of ATV, depending on their age and weight. The medication was administered as 50 mg, 100 mg, or 200 mg capsules or a powder formulation, depending on which study arm participants were in.

Ritonavir: Administered as 100 mg capsules or oral solution.

ATV Final Recommended Dose: 310mg/m^2

Step I: Group 5a (ATV Final Dose: 310mg/m^2 Powder + RTV)

Group 5a enrolled participants between 91 days of age and 180 days of age. They received ATV (powder), ritonavir, and two NRTIs.

ATV: Participants received varying doses of ATV, depending on their age and weight. The medication was administered as 50 mg, 100 mg, or 200 mg capsules or a powder formulation, depending on which study arm participants were in.

Ritonavir: Administered as 100 mg capsules or oral solution.

ATV Final Recommended Dose: 310mg/m^2

Step I: Group 6 (ATV Final Dose: 310mg/m^2 Powder + RTV)

Group 6 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (powder), ritonavir, and two NRTIs.

ATV: Participants received varying doses of ATV, depending on their age and weight. The medication was administered as 50 mg, 100 mg, or 200 mg capsules or a powder formulation, depending on which study arm participants were in.

Ritonavir: Administered as 100 mg capsules or oral solution.

ATV Final Recommended Dose: 310mg/m^2

Step I: Group 7 (ATV Final Dose: 205mg/m^2 Capsule + RTV)

Group 7 enrolled participants between 2 years and 1 day of age and 13 years of age. They received ATV (capsule), ritonavir, and two NRTIs.

ATV: Participants received varying doses of ATV, depending on their age and weight. The medication was administered as 50 mg, 100 mg, or 200 mg capsules or a powder formulation, depending on which study arm participants were in.

Ritonavir: Administered as 100 mg capsules or oral solution.

ATV Final Recommended Dose: 205mg/m^2

Step I: Group 8 (ATV Final Dose: 205mg/m^2 Capsule + RTV)

Group 8 enrolled participants between 13 years and 1 day of age and 21 years of age. They received ATV (capsule), ritonavir, and two NRTIs.

ATV: Participants received varying doses of ATV, depending on their age and weight. The medication was administered as 50 mg, 100 mg, or 200 mg capsules or a powder formulation, depending on which study arm participants were in.

Ritonavir: Administered as 100 mg capsules or oral solution.

ATV Final Recommended Dose: 205mg/m^2

Total Total of all reporting groups

Baseline Measures
    Step I: Group 3 (ATV Final Dose: 520mg/m^2 Capsule)     Step I: Group 4 (ATV Final Dose: 620mg/m^2 Capsule)     Step I: Group 5 (ATV Final Dose: 310mg/m^2 Powder + RTV)     Step I: Group 5a (ATV Final Dose: 310mg/m^2 Powder + RTV)     Step I: Group 6 (ATV Final Dose: 310mg/m^2 Powder + RTV)     Step I: Group 7 (ATV Final Dose: 205mg/m^2 Capsule + RTV)     Step I: Group 8 (ATV Final Dose: 205mg/m^2 Capsule + RTV)     Total  
Number of Participants  
[units: participants]
  21     25     21     11     26     24     14     142  
Age  
[units: years]
Median (Full Range)
  8.6   (6.3 to 12.5)     14.3   (13.1 to 20.2)     1.2   (0.3 to 2.0)     0.4   (0.3 to 0.5)     4.4   (2.0 to 12.0)     9   (5.6 to 12.7)     17   (13.9 to 21)     7   (0.3 to 21)  
Gender  
[units: participants]
               
Female     11     18     8     6     12     11     9     75  
Male     10     7     13     5     14     13     5     67  
Race/Ethnicity, Customized  
[units: participants]
               
White Non-Hispanic     4     0     0     0     1     0     0     5  
Black Non-Hispanic     14     17     18     10     18     17     8     102  
Hisp-Regardless of Race     3     7     2     1     7     5     5     30  
More than one race     0     0     1     0     0     1     1     3  
Unavailable     0     1     0     0     0     1     0     2  
CD4 Count  
[units: cells/mm^3]
Median (Full Range)
  374   (105 to 963)     286   (11 to 476)     1306   (392 to 4875)     2125   (583 to 2715)     466   (62 to 1537)     540   (24 to 1800)     334   (1 to 548)     457   (1 to 4875)  
CD4 Percent  
[units: percentage of total lymphocytes]
Median (Full Range)
  18   (7 to 36)     14   (1 to 39)     19   (7 to 53)     35   (10 to 46)     16   (2 to 34)     21   (1 to 43)     19   (0 to 40)     18   (0 to 53)  
HIV-RNA  
[units: log10 copies/ml]
Median (Full Range)
  4.4   (3.5 to 5)     4.7   (3.6 to 6.5)     5   (4.4 to 5.6)     5   (5 to 6.5)     4.8   (4.1 to 5.1)     4.5   (3.4 to 5)     4.3   (3.5 to 5)     4.8   (3.4 to 6.5)  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants Who Experienced a Safety Endpoint of Interest Attributed to ATV   [ Time Frame: From study entry up to week 96 ]

2.  Primary:   Number of Participants Who Died   [ Time Frame: From study entry up to week 96 ]

3.  Primary:   Pharmacokinetic (PK) Parameter: Area Under the Curve (AUC24h)   [ Time Frame: Week 1 (Day 7) Intensive PK-24hr (Pre-Dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose) ]

4.  Primary:   Pharmacokinetic (PK) Parameter: Minimum Plasma Concentration (C24)   [ Time Frame: Week 1 (Day 7) Intensive PK-24hr (Pre-dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose) ]

5.  Primary:   Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax)   [ Time Frame: Week 1 (Day 7) Intensive PK-24 hr (Pre-dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose) ]

6.  Primary:   Pharmacokinetic (PK) Parameter: Clearance (CL/F)   [ Time Frame: Week 1 (Day 7) Intensive PK-24 hr (Pre-dose, 1, 2, 3, 4, 6, 8, and 12 hours post-dose and the following day at 24-hours post-dose) ]

7.  Secondary:   Percentage of Participants With HIV RNA <400 Copies/mL at Week 24   [ Time Frame: Week 24 ]

8.  Secondary:   Percentage of Participants With HIV RNA <400 Copies/mL at Week 48   [ Time Frame: Week 48 ]

9.  Secondary:   Percentage of Participants With HIV RNA <400 Copies/mL at Week 96   [ Time Frame: Week 96 ]

10.  Secondary:   Change in CD4 Count (Cells/mm^3) From Baseline to Week 20   [ Time Frame: Baseline, Week 20 ]

11.  Secondary:   Change in CD4 Count (Cells/mm^3) From Baseline to Week 48   [ Time Frame: Baseline, Week 48 ]

12.  Secondary:   Change in CD4 Count (Cells/mm^3) From Baseline to Week 96   [ Time Frame: Baseline, Week 96 ]

13.  Secondary:   Change in CD4 Percent From Baseline to Week 20   [ Time Frame: Baseline, Week 20 ]

14.  Secondary:   Change in CD4 Percent From Baseline to Week 48   [ Time Frame: Baseline, Week 48 ]

15.  Secondary:   Change in CD4 Percent From Baseline to Week 96   [ Time Frame: Baseline, Week 96 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  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: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
phone: (919) 405-1429
e-mail: mallen@fhi360.org


Publications:
Aldrovandi G, Samson P, Fenton T, Schnittman S, Rutstein R, Ortiz A and the Pediatric AIDS Clinical Trial 1020A Group. Resistance to Atazanavir (ATV), Lopinavir (LPV), Tenofovir (TFV) Among Heavily Experienced Pediatric Patients. 12th International Symposium on HIV and Emerging Infectious Diseases in Toulon, France, June 2002.
Aldrovandi G, Samson P, Fenton T, Schnittman S, and Rutstein R for the P1020A Team. Genotypic and phenotypic resistance to BMS232632 (Atazanavir-ATV), among heavily experienced pediatric patients who were ATV-naïve. 9th Conference on Retroviruses and Opportunistic Infections, February 24 - 28, 2002, Seattle, WA.
Kiser J, Rutstein R, Aldrovandi G, Samson P, Graham B, Schnittman S, Smith M, Mofenson L, Fletcher C, and the PACTG 1020A Study Team. Pharmacokinetics of atazanavir/ritonavir in HIV-infected infants, children, and adolescents: PACTG 1020A. 12th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 2005.
Kiser J, Rutstein R, Samson P, Graham B, Aldrovandi G, Mofenson L, Smith E, Zhang J, Biguenet S, Fletcher C, and the P1020A team. Atazanavir dosing conversion and pharmacokinetics in HIV-infected children switching from atazanavir powder to capsules. 12 th International Workshop on Clinical Pharmacology of HIV Therapy, Miami, Florida, April 2011.
Meyers T, Rutstein R, Samson P, Violari A, Palmer M, Kiser J, Fletcher C, Fenton T, Mofenson L, Graham B, Schnittman S, Horga M, Aldrovandi G, for the PACTG 1020A Study. Treatment responses to atazanavir-containing HAART in a drug-naïve pediatric population in South Africa. 15th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 2008.
Rutstein R, Samson P, Aldrovandi G, Graham B, Schnittman S, Fletcher C, Kiser J, Smith E, Mofenson L, Fenton T, and the PACTG 1020A Study Team. Effect of atazanavir on serum cholesterol and triglyceride levels in HIV-infected infants, children, and adolescents: PACTG 1020A. 12th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 2005.
Rutstein R, Samson P, Fenton T, Kiser J, Fletcher C, Schnittman S, Mofenson L, Smith E, Graham B, Aldrovandi G, PACTG 1020A Study. The NIH PACTG Protocol 1020A: ATAZANAVIR (ATV), +/- RITONAVIR in HIV-Infected Infants, Children and Adolescents. Presented at the 14th Conference on Retrovirus and Opportunistic Infection (CROI), Los Angeles, CA, February, 2007.
Samson P, Rutstein R, Schnittman S, Ortiz A, Graham B, Fenton T, Aldrovandi G and the Pediatric AIDS Clinical Trials Group P1020A Study Team. Effects of Antiretroviral (ARV) Exposure and Genotypic (Geno) Mutations in Predicting Phenotypic Resistance (PRS) to Atazanavir (ATV), Lopinavir (LPV), and Tenofovir (TDF) in Patients Naïve to these Drugs. 13th International Symposium on HIV and Emerging Infectious Diseases, Toulon, France, June 2004.
Samson P, Rutstein R, Fenton T, Kiser J, Fletcher C, Schnittman S, Mofenson L, Smith E, Graham B, Aldrovandi G, and the PACTG 1020A Study Team. Changes in cholesterol and triglyceride levels among pediatric subjects treated with atazanavir, with or without ritonavir boosting: the 1020A NIH PACTG protocol. 13th Conference on Retroviruses and Opportunistic Infections, Denver, CO, February 2006.


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00006604     History of Changes
Other Study ID Numbers: P1020A
10037 ( Registry Identifier: DAIDS ES )
IMPAACT P1020A
PACTG P1020-A
ACTG P1020-A
Study First Received: December 6, 2000
Results First Received: January 29, 2016
Last Updated: March 7, 2016
Health Authority: United States: Food and Drug Administration