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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Valproic acid
Zidovudine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Valproic Acid, Zidovudine

Eligibility Criteria

18 Years - 50 Years (Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Tulane Univ Med School

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
July 29, 2008
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000629
Brief Title
The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.
Official Title
The Effects of Valproic Acid on Zidovudine Glucuronidation and Pharmacokinetics in HIV-Infected Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2003
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
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3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Valproic Acid, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
6 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Valproic acid
Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lertora JJL
Official's Role
Study Chair
Facility Information:
Facility Name
Tulane Univ Med School
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
701122699
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Lertora J, Akula S, Greenspan D, Rege A, Agrawal K, George W, Hyslop N. Valproic acid inhibits zidovudine glucuronidation in patients with HIV infection. Int Conf AIDS. 1992 Jul 19-24;8(3):100 (abstract no PuB 7307)
Results Reference
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PubMed Identifier
7924122
Citation
Lertora JJ, Rege AB, Greenspan DL, Akula S, George WJ, Hyslop NE Jr, Agrawal KC. Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 1994 Sep;56(3):272-8. doi: 10.1038/clpt.1994.137.
Results Reference
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Learn more about this trial

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

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