The Safety and Effectiveness of Valacyclovir HCl in the Treatment of Herpes Simplex or Varicella/Zoster Infections in HIV-1 Infected Children

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00001054
• Other study ID #: ACTG 253
• Secondary ID: 11230
• Status: Withdrawn
• Phase: Phase 1
• Est. completion date: January 2001

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

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2001
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chickenpox
• Communicable Diseases
• Herpes Simplex
• HIV Infections
• Infections

Intervention

Drug:
• Valacyclovir hydrochloride

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Glaxo Wellcome

References & Publications (2)

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. — View Citation

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. — View Citation