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Ritonavir and Indinavir in Children Failing Other Anti-HIV Treatment

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00012519
First received: March 10, 2001
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

Both ritonavir (RTV) and indinavir (IDV) are approved by the FDA to treat HIV, but IDV has not been approved for use in children and the doses for the combination of the two drugs has not been studied in children. The purpose of this study is to find a combination of RTV and IDV that is safe, well tolerated, and produces drug levels in the blood of children that are comparable to effective drug levels in the blood of adults. The effectiveness of the drug combination in decreasing the amount of virus in the body will also be studied. The children enrolled in this study will have high HIV viral loads despite taking anti-HIV drugs.


Condition Intervention Phase
HIV Infections
Drug: indinavir sulfate
Drug: ritonavir
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Ritonavir and Indinavir in Children Failing Other Antiretroviral Therapy

Resource links provided by NLM:


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

Enrollment: 29
Study Completion Date: July 2005
Detailed Description:

Combination regimens of RTV and IDV in adults offer the benefit of two potent antiretroviral agents, convenience of twice-daily dosing, unrestricted timing of meals, and fewer renal complications. There are limited, largely anecdotal data from children suggesting that initial virologic response can also be attained in children given IDV with RTV, but there are not sufficient pharmacokinetic data to define appropriate dose regimens. This study will evaluate the clinical feasibility of a combination RTV and IDV regimen for children.

Patients will be stratified on the basis of age/Tanner stage and ability to swallow intact capsules. Patients will be randomized to either Balanced Dose or Low Dose RTV treatment arms. Patients in the Balanced Dose Arm will receive RTV and IDV in approximately equal doses. The Low Dose RTV Arm will receive a dosing ratio of RTV:IDV of approximately 1:3. Patients will have scheduled study visits every 4 weeks for 6 months, then every 3 months for approximately 18 months. Study visits will consist of a medical history, physical exam, and blood and urine tests. Patients will have intensive pharmacokinetic analysis at Week 4 (or 2 weeks after a stable dose of study drugs has been reached) and Week 16. Study visits that include pharmacokinetic analysis will last 9 to 13 hours.

At each study visit, patients will be closely assessed for drug toxicity and virologic response. At the end of the study, patients with good virologic response and no evidence of toxicity may choose to enter a 48 week extension phase and continue taking the combination regimen.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • HIV infection
  • HIV RNA levels > 10,000 copies/ml within 30 days prior to study entry
  • Anti-HIV drug therapy failure while on the same anti-HIV drugs for more than 16 weeks
  • Body size above a certain limit (body surface area > 0.48 m2)
  • Acceptable methods of contraception
  • Consent of parent or legal guardian

Exclusion Criteria

  • Unable to determine HIV genotypic resistance
  • HIV resistant to IDV or RTV at study screening
  • Previously received IDV and RTV at the same time
  • Need treatment with any medication prohibited by the study
  • Glucocorticoids for more than 14 days at study entry
  • Cancer requiring chemotherapy
  • Drugs affecting the immune system, other than IVIG, within 3 months of study entry
  • Certain abnormal laboratory results at study entry
  • Pregnant or breast-feeding
  • Unable to be followed at a PACTG center during the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00012519

Locations
United States, District of Columbia
Howard Univ. Washington DC NICHD CRS
Washington, District of Columbia, United States, 20060
United States, Florida
Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy
Gainesville, Florida, United States, 32610
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States, 32209
United States, Illinois
Chicago Children's CRS
Chicago, Illinois, United States, 606143394
United States, New York
Columbia IMPAACT CRS
New York, New York, United States, 10032
Harlem Hosp. Ctr. NY NICHD CRS
New York, New York, United States, 10037
Metropolitan Hosp. Ctr.
New York, New York, United States, 10029
SUNY Upstate Med. Univ., Dept. of Peds.
Syracuse, New York, United States, 13210
United States, Tennessee
St. Jude/UTHSC CRS
Memphis, Tennessee, United States, 381052794
United States, Texas
Texas Children's Hosp. CRS
Houston, Texas, United States, 77030
United States, Virginia
VCU Health Systems, Dept. of Peds
Richmond, Virginia, United States, 23219
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 009367344
Sponsors and Collaborators
Investigators
Study Chair: Ellen Chadwick
Study Chair: Ram Yogev
Study Chair: Stephen Pelton
Study Chair: Elaine Abrams
  More Information

Additional Information:
Publications:
Chadwick EG, Rodman JH, Samson P, Fenton T, Abrams EJ, Nowak B, Pelton SI, Lavoie S, Knapp K, Bambji M, Yogev R, PACTG 1013 Team. Antiviral Activity, Tolerance and Pharmacokinetics of Indinavir with Two Doses of Ritonavir as Salvage Therapy in Children. 10th Conference on Retroviruses and Oppurtunistic Infections. Feb 2003. Abstract 875.

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00012519     History of Changes
Other Study ID Numbers: P1013, 10191, ACTG P1013, PACTG P1013
Study First Received: March 10, 2001
Last Updated: May 17, 2012
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
HIV Protease Inhibitors
Ritonavir
Indinavir
Anti-HIV Agents
Viral Load
Pharmacokinetics
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Indinavir
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014