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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00006604

Purpose

The purpose of this study is to find a safe and tolerable dose of the protease inhibitor (PI) atazanavir (ATV), with or without a low-dose boost of the PI ritonavir (RTV), when taken with other anti-HIV drugs in HIV infected infants, children, and adolescents.

Advancements in anti-HIV drugs for HIV infected children and adolescents have been hard to make, in part because these patients often do not take the drugs as prescribed. ATV may be a better option because it is available in the form of powder which children and adolescents may be more willing to take regularly. Using a low dose of RTV as a boosting agent for ATV may also increase the chances of virologic response of highly active antiretroviral treatment (HAART)-experienced patients. This study will try to find safe and tolerable doses of ATV with or without low-dose RTV boost in infants, children, and adolescents. For this study, participants will be enrolled in the U.S. and South Africa.

Condition	Intervention	Phase
HIV Infections	Drug: Atazanavir Drug: Ritonavir	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study
Official Title:	Phase I/II, Open-Label, Pharmacokinetic and Safety Study of a Novel Protease Inhibitor (BMS 232632, Atazanavir, ATV, ReyatazTM) in Combination Regimens in Antiretroviral Therapy (ART)-Naive and -Experienced HIV-Infected Infants, Children, and Adolescents

Resource links provided by NLM:

MedlinePlus related topics: AIDS AIDS Medicines

Drug Information available for: Ritonavir BMS 232632 Atazanavir sulfate

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Grade 3 or 4 toxicities as defined in protocol [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Pharmacokinetic parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Viral load [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Cd4 count and percentage [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
CD8 count and percentage [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Markers of cellular activation [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	157
Study Start Date:	July 2005
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Part A: Active Comparator Participants will receive ATV along with 2 other antiretrovirals as determined by study investigators. Participants in this group will be stratified by age and may receive ATV as either a powder or capsule.	Drug: Atazanavir protease inhibitor
Part B: Active Comparator Participants in this group will receive ATV plus a low-dose RTV booster and 2 other antiretrovirals as determined by study investigators. Participants in this group will be stratified by age and may receive ATV as a powder or capsule.	Drug: Atazanavir protease inhibitor Drug: Ritonavir protease inhibitor

Detailed Description:

Advancements in HAART for HIV-infected children and adolescents are hindered by patient nonadherence. The availability of a powder formulation and the once-daily dosing schedule make ATV an attractive agent for improved adherence in pediatric treatment regimens. This study is designed to provide pharmacokinetic (PK) data to guide dosing recommendations for ATV, when given concurrently with or without low-dose RTV boost, in infants, children, and adolescents. During the study, the safety and tolerance of ATV (with or without low-dose RTV) will be closely monitored, and virologic efficacy data will be obtained.

There are two parts to this study. Step I will take place in the U.S. and South Africa, and will be further divided into two sets of groups, Parts A and B. Part A participants will receive ATV only and Part B participants will receive ATV with low-dose RTV boost. All participant will receive ATV once a day with 2 other antiretroviral drugs (not provided by the study). In Part B only, participants will receive ATV with a low dose of RTV. Participants will be placed into 1 of 8 groups (Groups 1 to 4 for Part A; Groups 5 to 8 for Part B) with respect to age and study drug formulation. Participants in Groups 1 and 5 will be infants between ages 3 months and 1 day (91 days) and 2 years (less than or exactly 730 days) and will take ATV in powder form. Participants in Groups 2, 3, 6, and 7 will be children between 2 years and 1 day (731 days) old and 13 years old. Groups 2 and 6 will receive ATV in powder form, while Groups 3 and 7 will receive the capsule form. Patients in Groups 4 and 8 will be adolescents between 13 years and 1 day old up to 21 years old (not including the 22nd birthday) and will take ATV in capsule form. As of 01/02/2008 a new group, 5A has been opened for enrollment. Participants in Group 5A will be between 3 months and 6 months old and will take ATV in powder form plus a low dose RTV booster.

For each group, enrollment will start with five participants per group. All participants will be evaluated for PK and safety criteria, adjusting the dose of ATV until one is found that passes both sets of criteria. Then five additional participants will be enrolled, with enrollment continuing for each group once all participants within that group meet the PK criteria. For groups receiving RTV (Groups 5 to 8), additional criteria must be met for each dose of ATV studied. In addition to the PK and safety evaluations, 24-hour post-dose concentrations (Cmin) will be monitored in the first 10 participants enrolled for a dose of ATV before more participants can be enrolled and studied at that same dose. Clinic visits will be every 4 weeks through Week 48, then every 8 weeks until the last participant to enroll in the study has reached Week 96 of his/her treatment. If, after 56 weeks, a participant has a toxic reaction to a nucleoside/tide reverse transcriptase inhibitor (NRTI) in their medication regimen, the regimen may be changed to a different NRTI. At every visit, participants will undergo a complete medical history and physical exam, cardiac conduction evaluation, and urine and blood collection. Participants of childbearing age will have a pregnancy test performed at each visit.

Step II will be open only to South African participants of Step I who have responded to treatment by the end of Step I. All such participants will be given ATV in capsule form at the same dose they received at the end of Step I, as well as the other antiretrovirals they were receiving during Step I. Step II will continue until ATV is approved in South Africa and readily available by individual prescription, and participants will have a study visit every 12 weeks.

Eligibility

Ages Eligible for Study:	3 Months to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

[Note: Groups 1,2,3,4,5,6,7, and 8 are no longer open to accrual.]

Have HIV infection.
Have a viral load (amount of HIV in the blood) of 5,000 copies/ml or more.
Are able to take 2 nucleoside reverse transcriptase inhibitors (NRTIs) that they have never taken before.
Take a test showing they can respond to atazanavir.
Are able and willing to swallow the study drugs.
Are 3 months and 1 day (91 days) to 21 years old.
Agree to practice abstinence or use effective barrier method of birth control if they are able to become pregnant.
Have signed consent of parent or guardian if under 18 years of age.
Are willing to undergo complete cardiac conduction evaluation at screening.
For Step II, are South African participants from Step I that are virologically successful by Week 96 of the last study patient enrolled in their respective part of Step I.

Exclusion Criteria:

Have hepatitis.
Have a serious infection that requires treatment at the time of study entry.
Are allergic to atazanavir.
Are receiving chemotherapy for cancer.
Have any serious conditions (other than HIV infection) at study entry that might affect the results of the study.
Are pregnant or breastfeeding.
Show toxicity at study entry.
Are receiving certain drugs or treatments.
Are receiving pentamidine (by vein) for Pneumocystis carinii pneumonia within 3 months of study entry; ongoing monthly treatment with orally inhaled pentamidine for prophylaxis is not excluded.
Have a history of significant cardiac abnormalities or dysfunction.
For Step II, virologic failure or the investigator deems discontinuation appropriate based on toxicity/tolerability.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006604

Show 46 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Investigators

Study Chair:	Richard Rutstein, MD	Children's Hospital of Philadelphia
Study Chair:	Grace Aldrovandi, MD	Children's Hospital Los Angeles
Study Chair:	Mark W. Kline, MD	Baylor College of Medicine

More Information

Additional Information:

Click here for more information about atazanavir This link exits the ClinicalTrials.gov site

Click here for more information about ritonavir This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Barreiro P, Rendon A, Rodriguez-Novoa S, Soriano V. Atazanavir: the advent of a new generation of more convenient protease inhibitors. HIV Clin Trials. 2005 Jan-Feb;6(1):50-61. Review.

Fraaij PL, van Kampen JJ, Burger DM, de Groot R. Pharmacokinetics of antiretroviral therapy in HIV-1-infected children. Clin Pharmacokinet. 2005;44(9):935-56.

Kashuba AD. Drug-drug interactions and the pharmacotherapy of HIV infection. Top HIV Med. 2005 Jun-Jul;13(2):64-9. Review.

Moyle G. Overcoming obstacles to the success of protease inhibitors in highly active antiretroviral therapy regimens. AIDS Patient Care STDS. 2002 Dec;16(12):585-97. Review.

Pontali E. Facilitating adherence to highly active antiretroviral therapy in children with HIV infection: what are the issues and what can be done? Paediatr Drugs. 2005;7(3):137-49. Review.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	IMPAACT P1020A, PACTG P1020-A, ACTG P1020-A
Study First Received:	December 6, 2000
Last Updated:	January 31, 2010
ClinicalTrials.gov Identifier:	NCT00006604 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Dose-Response Relationship, Drug
Drug Therapy, Combination
Drug Administration Schedule
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors

Anti-HIV Agents
Pharmacokinetics
Treatment Experienced
Treatment Naive

Additional relevant MeSH terms:

Atazanavir
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
HIV Protease Inhibitors

Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on February 08, 2010