The Safety and Effectiveness of Valacyclovir HCl in the Treatment of Herpes Simplex or Varicella/Zoster Infections in HIV-1 Infected Children
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Herpes Simplex; HIV Infections; Chickenpox
Intervention: Valacyclovir hydrochloride (Drug)
Phase: Phase 1
Status: Terminated
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Keller MA, Study Chair
Bryson Y, Study Chair
Gershon A, Study Chair
Summary
To obtain tolerance, safety, and pharmacokinetic data for oral valacyclovir hydrochloride (
256U87 ) in HIV-1 infected children with herpes simplex virus infections ( cold sores )
and/or varicella / zoster virus infections ( chicken pox / shingles ).
Varicella and zoster are common problems in HIV-infected children. It is believed that
chronic oral therapy with acyclovir may result in subtherapeutic concentrations of acyclovir,
resulting in resistance to that drug. Valacyclovir hydrochloride, which converts to acyclovir
in the body, increases acyclovir bioavailability by 3-5 fold.
Clinical Details
Official title: A Phase I Trial to Evaluate the Pharmacokinetics, Safety, and Tolerance of Valacyclovir HCl in HIV-1 Infected Children With Herpes Simplex Infections or Varicella/Zoster Infections
Study design: Treatment, Open Label, Pharmacokinetics Study
Detailed description:
Varicella and zoster are common problems in HIV-infected children. It is believed that
chronic oral therapy with acyclovir may result in subtherapeutic concentrations of acyclovir,
resulting in resistance to that drug. Valacyclovir hydrochloride, which converts to acyclovir
in the body, increases acyclovir bioavailability by 3-5 fold.
In the first cohort, patients with stable herpes simplex virus receive valacyclovir
hydrochloride at 1 of 2 doses, depending on body surface area (BSA), for 10 days. If
acceptable safety is seen at this dose level, a second cohort of patients with stable herpes
simplex virus receive a higher dose, depending on BSA, for 10 days. A third cohort of
patients with varicella or zoster receive a selected dose based on results from the previous
cohorts.
Eligibility
Minimum age: 4 Years.
Maximum age: 12 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria
Concurrent Medication:
Allowed:
- Antiretrovirals.
- PCP prophylaxis.
- IVIG, G-CSF, and erythropoietin.
Concurrent Treatment:
Allowed:
- Transfusions.
Patients must have:
- Localized mucocutaneous herpes simplex OR undisseminated varicella or zoster.
- HIV positive. NOTE: Varicella patients must NOT have AIDS.
- CD4 count >= 100 cells/mm3 (herpes simplex or zoster patients) OR >= 250 cells/mm3
(varicella patients).
- BSA > 0. 6 m2.
- Ability to swallow solid dosage formulations.
Prior Medication:
Allowed:
- Prior VZV immune globulin and/or IVIG.
- Antiretrovirals if at a stable dose for at least 14 days.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
- Clinical evidence of pneumonitis.
- Severe abdominal pain or back pain.
- Encephalopathy.
- Hemorrhagic varicella.
- Zoster involving ophthalmic branch of trigeminal nerve.
- Severe gastrointestinal disorder.
Concurrent Medication:
Excluded:
- Agents with potential activity against HSV or VZV, such as acyclovir, famciclovir,
ganciclovir, foscarnet, and sorivudine.
- Probenecid.
- Aspartamine within 48 hours prior to pharmacokinetic samplings.
Patients with the following prior conditions are excluded:
- Grade 2 creatinine value within the past 30 days.
- Grade 3 hematologic or hepatic values within the past 30 days.
- Prior hypersensitivity and/or allergic reaction to acyclovir.
- Grade 3 or 4 mental status changes within the past 30 days.
Prior Medication:
Excluded:
- Acyclovir within 1 week prior to study entry.
- Steroids within 4 weeks prior to onset of varicella lesions.
Locations and Contacts
Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico
UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States
Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles, California 905022004, United States
Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, United States
Children's Hosp of Oakland, Oakland, California 946091809, United States
UCLA Med Ctr / Pediatric, Los Angeles, California 900951752, United States
Children's Hosp of Los Angeles/UCLA Med Ctr, Los Angeles, California 900276016, United States
Children's Hosp of Washington DC, Washington, District of Columbia 200102916, United States
Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States
Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States
Children's Hosp of Boston, Boston, Massachusetts 021155724, United States
Univ of Rochester Med Ctr, Rochester, New York 14642, United States
Harlem Hosp Ctr, New York, New York 10037, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Columbia Presbyterian Med Ctr, New York, New York 10032, United States
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York, New York 10032, United States
Duke Univ Med Ctr, Durham, North Carolina 277103499, United States
Med Univ of South Carolina, Charleston, South Carolina 294253312, United States
Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States
Additional Information
Related publications: von Seidlein L, Gillette SG, Bryson Y, Frederick T, Mascola L, Church J, Brunell P, Kovacs A, Deveikis A, Keller M. Frequent recurrence and persistence of varicella-zoster virus infections in children infected with human immunodeficiency virus type 1. J Pediatr. 1996 Jan;128(1):52-7. Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella-zoster virus infection. Ann Intern Med. 1999 Jun 1;130(11):922-32. Review.
Last updated: June 23, 2005
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