The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000629
First received: November 2, 1999
Last updated: July 29, 2008
Last verified: October 2003

November 2, 1999
July 29, 2008
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Complete list of historical versions of study NCT00000629 on ClinicalTrials.gov Archive Site
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The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.
The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.

Primary objective: To study the pharmacokinetic interaction between zidovudine (AZT) and valproic acid in asymptomatic HIV-infected patients, characterizing AZT's oral bioavailability, plasma elimination half-time, plasma levels, and urinary excretion of AZT, 5'-O-glucuronide (GAZT), and 3'-amino-3'-deoxythymidine (AMT). Secondary objective: To establish the safety of short-term administration of AZT and valproic acid in combination with regard to hematologic parameters and liver function in asymptomatic HIV-infected patients.

Preliminary studies using human liver tissue have shown that valproic acid inhibits the metabolic inactivation of zidovudine (AZT), which may prolong the plasma half-life of AZT and thus prolong the duration of the drug's effects in the body.

Preliminary studies using human liver tissue have shown that valproic acid inhibits the metabolic inactivation of zidovudine (AZT), which may prolong the plasma half-life of AZT and thus prolong the duration of the drug's effects in the body.

Six asymptomatic HIV-infected patients are treated with AZT orally every 8 hours on days 1 through 4, then with a single dose on day 5 (after 8 hours of fasting), followed by pharmacokinetic sampling. On days 6 through 9, patients receive AZT orally every 8 hours in combination with valproic acid (lowest dose in the first 5 patients and a higher dose in patients 6 and 7) orally every 8 hours. On day 10, AZT and 1 of the 2 doses of valproic acid are given orally as single doses, followed by pharmacokinetic sampling. AZT is continued alone orally every 8 hours on days 11 through 14, then resumed at the patient's usual dose beginning on day 15. Per 03/09/92 amendment, dosing schedule may be modified slightly to accommodate patients with scheduling conflicts.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Valproic acid
  • Drug: Zidovudine
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
6
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Inclusion Criteria

Concurrent Medication:

Allowed:

Vitamins if already being taken prior to start of therapy.

Patients must have:

  • Asymptomatic HIV infection.
  • CD4 count between 300 and 650.

Prior Medication:

Required:

  • AZT at doses between 500 and 1200 mg/day for at least 6 weeks prior to enrollment.

Allowed:

  • Aspirin, Tylenol, or ibuprofen up to 48 hours prior to start of therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Positive Hepatitis B surface antigen or clinical evidence of chronic active hepatitis of any type.
  • Signs or symptoms of HIV infection including oral candidiasis, history of multidermatomal zoster, unexplained weight loss in excess of 10 percent body weight in the past 6 months, chronic diarrhea, or history of AIDS-defining opportunistic infections.

Concurrent Medication:

Excluded:

  • Concomitant medications (other than AZT) for the 14 days prior to start of therapy.

Patients with the following prior conditions are excluded:

  • History of AZT intolerance including hematologic, hepatic, and/or neurologic toxicity.
  • History of seizures.
  • History of any antiepileptics within the past 10 years.
  • History of abnormal bleeding or intrinsic or extrinsic coagulopathy.
  • Signs or symptoms of HIV infection including oral candidiasis, history of multidermatomal zoster, unexplained weight loss in excess of 10 percent body weight in the past 6 months, chronic diarrhea, or history of AIDS-defining opportunistic infections.

Prior Medication:

Excluded:

  • Antiepileptics within the past 10 years.
  • Prior valproic acid.
  • Concomitant medications (other than AZT) within 14 days of enrollment.
Male
18 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00000629
ACTG 191
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National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: Lertora JJL
National Institute of Allergy and Infectious Diseases (NIAID)
October 2003

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP