Ritonavir and Indinavir in Children Failing Other Anti-HIV Treatment

HIV Infections Clinical Trial

Official title:

A Phase I/II Trial of Ritonavir and Indinavir in Children Failing Other Antiretroviral Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00012519
• Other study ID #: P1013
• Secondary ID: 10191ACTG P1013P
• Status: Completed
• Phase: Phase 1/Phase 2
• Est. completion date: July 2005

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• indinavir sulfate

• ritonavir

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
United States	Chicago Children's CRS	Chicago	Illinois
United States	Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy	Gainesville	Florida
United States	Texas Children's Hosp. CRS	Houston	Texas
United States	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	St. Jude/UTHSC CRS	Memphis	Tennessee
United States	Columbia IMPAACT CRS	New York	New York
United States	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York
United States	Metropolitan Hosp. Ctr.	New York	New York
United States	VCU Health Systems, Dept. of Peds	Richmond	Virginia
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York
United States	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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.

Saah AJ, Winchell GA, Nessly ML, Seniuk MA, Rhodes RR, Deutsch PJ. Pharmacokinetic profile and tolerability of indinavir-ritonavir combinations in healthy volunteers. Antimicrob Agents Chemother. 2001 Oct;45(10):2710-5. — View Citation

van Rossum AM, de Groot R, Hartwig NG, Weemaes CM, Head S, Burger DM. Pharmacokinetics of indinavir and low-dose ritonavir in children with HIV-1 infection. AIDS. 2000 Sep 29;14(14):2209-10. — View Citation

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