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A Study to Evaluate the Effects of Different Methods of Birth Control on the Drug Actions of Zidovudine (an Anti-HIV Drug) in HIV-Positive Women and to Compare Zidovudine Metabolism in Men and Women

Primary Purpose

HIV Infections

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
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 Drug Interactions, Zidovudine, Sex Factors, Reverse Transcriptase Inhibitors, Contraceptives, Oral, Progestational Hormones, Synthetic, Anti-HIV Agents, Viral Load, Estrogens

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Men and women may be eligible for this study if they: Are HIV positive. Women may be eligible for this study if they: Have regular periods and a normal gynecological exam, (including a Pap smear and mammogram). Enter the study between Days 10 and 18 of the first day of their last period. Are willing to use either the Pill or Depo-Provera as birth control. Have a negative pregnancy test within 14 days prior to study. Exclusion Criteria Men and women will not be eligible for this study if they: Cannot take ZDV for any reason. Have cancer. Are taking stavudine. Women will not be eligible for this study if they: Cannot take the Pill or Depo-Provera. Are pregnant or nursing. Are receiving nelfinavir and want to enroll in Step 2. Have a history of chronic high blood pressure, thrombophlebitis, and/or pulmonary emboli if participating in Step 2 of the study. (This study has been changed so that women with certain criteria are excluded from participating in Step 2.)

Sites / Locations

  • San Francisco AIDS Clinic / San Francisco Gen Hosp
  • Univ of Florida Health Science Ctr / Pediatrics
  • Children's Hosp at Albany Med Ctr
  • SUNY / Erie County Med Ctr at Buffalo
  • Univ of North Carolina
  • Univ of Washington

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
March 1, 2011
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000897
Brief Title
A Study to Evaluate the Effects of Different Methods of Birth Control on the Drug Actions of Zidovudine (an Anti-HIV Drug) in HIV-Positive Women and to Compare Zidovudine Metabolism in Men and Women
Official Title
The Effect of Oral and Injectable Contraceptives (Norethindrone/Ethinyl Estradiol, Medroxyprogesterone Acetate) and Gender on Plasma and Intracellular Zidovudine Pharmacokinetics
Study Type
Interventional

2. Study Status

Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
October 2005 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to look at the effects of different methods of birth control (oral and injectable) on how the body absorbs, makes available, and removes zidovudine (ZDV). This study will also evaluate the differences in men and women in how the body absorbs, makes available, and removes ZDV. Past research has shown that the effectiveness of ZDV as an anti-HIV drug might be decreased in individuals who use certain methods of birth control. ZDV may also have different effects in men compared to women.
Detailed Description
Oral contraceptives have been shown to substantially enhance the glucuronidation of several compounds. One study reported enhanced glucuronidation of oxazepam, a compound that is conjugated via the same UDP-glucuronyl transferase isozyme responsible for ADV glucuronidation, suggesting that ZDV metabolism may be altered by concomitant oral contraceptive use. This potential enhancement of ZDV metabolism by oral contraceptives is expected to result in decreased plasma levels of the parent compound which may lead to diminished clinical efficacy in women using these drugs. It remains unclear whether the progesterone and/or estrogen component of oral contraceptives results in the observed glucuronidation changes. This open-label, pharmacokinetic trial is conducted in 2 steps. [AS PER AMENDMENT 6/12/01: The Depo-Provera IM group in Step 2 is filled. Female patients who choose to participate in Step 2 may enroll only in the Ortho-Novum 1/35 PO group.] [AS PER AMENDMENT 11/13/00: Female patients may choose to participate in Step 1 alone or both Steps 1 and 2.] Male patients may participate in Step 1 only as the control arm of the study. In Step 1, patients are stratified by sex; in Step 2, female patients are stratified by their choice of contraception (i.e., oral norethindrone/ethinyl estradiol [Ortho-Novum 1/35] or injectable medroxyprogesterone acetate [Depo-Provera]). Step 1 (males and females): At entry, all patients are randomized to receive ZDV either orally or orally and intravenously (IV) on Days 7 and 8. Female patients begin the study (Day 0) between days 10-18 after the first day of their last menstrual period (LMP) (Cycle 1). At time of enrollment, female patients [AS PER AMENDMENT 11/13/00: who plan to participate in Step 2] choose the form of birth control instituted in Step 2: Depo-Provera or Ortho-Novum 1/35. Male patients may enter Step 1 at any time. Patients continue taking their other pre-study antiretroviral drugs during Step 1. [AS PER AMENDMENT 6/3/99: Patients taking nelfinavir may participate only in the Depo-Provera arm.] Days 0-6: All patients receive oral ZDV. Day 7: Patients are randomized to receive: Arm 1 (females): oral ZDV for a total of 3 doses. Arm 2 (females): ZDV IV, then ZDV orally for a total of 2 oral doses. Arm 3 (males): control arm. Half of the male patients receive ZDV as in Arm 1 and the other male patients receive ZDV as in Arm 2. Day 8: Patients on all 3 arms receive the alternate form of ZDV to that received on Day 7. Day 9: Female patients resume their pre-study method of administration of ZDV. Male patients conclude their participation in the study on Day 8. Step 2 (females [AS PER AMENDMENT 11/13/00: opting to participate in Step 2]): At the onset of their second menstrual period (Cycle 2) since starting study, female patients start their choice of Ortho-Novum 1/35 or intramuscularly administered Depo-Provera [AS PER AMENDMENT 6/12/01: Enrollment for Depo-Provera is closed]. Contraceptive therapy continues throughout Step 2. Step 2 Days 0-6: Between days 7-11 [AS PER AMENDMENT 6/3/99: Between days 7-18] of the third menstrual cycle (Cycle 3) since starting study, female patients continue their pre-study antiretroviral therapy (as done in Step 1) and begin another course of ZDV standard therapy 3 times daily. Days 7-8: Patients receive the original method of administration of ZDV (as randomized at study entry). Female patients return for a final safety visit within 1 week of completing study Day 8 of Step 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Drug Interactions, Zidovudine, Sex Factors, Reverse Transcriptase Inhibitors, Contraceptives, Oral, Progestational Hormones, Synthetic, Anti-HIV Agents, Viral Load, Estrogens

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Enrollment
42 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Men and women may be eligible for this study if they: Are HIV positive. Women may be eligible for this study if they: Have regular periods and a normal gynecological exam, (including a Pap smear and mammogram). Enter the study between Days 10 and 18 of the first day of their last period. Are willing to use either the Pill or Depo-Provera as birth control. Have a negative pregnancy test within 14 days prior to study. Exclusion Criteria Men and women will not be eligible for this study if they: Cannot take ZDV for any reason. Have cancer. Are taking stavudine. Women will not be eligible for this study if they: Cannot take the Pill or Depo-Provera. Are pregnant or nursing. Are receiving nelfinavir and want to enroll in Step 2. Have a history of chronic high blood pressure, thrombophlebitis, and/or pulmonary emboli if participating in Step 2 of the study. (This study has been changed so that women with certain criteria are excluded from participating in Step 2.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesca Aweeka
Official's Role
Study Chair
Facility Information:
Facility Name
San Francisco AIDS Clinic / San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
Univ of Florida Health Science Ctr / Pediatrics
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Children's Hosp at Albany Med Ctr
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
SUNY / Erie County Med Ctr at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

A Study to Evaluate the Effects of Different Methods of Birth Control on the Drug Actions of Zidovudine (an Anti-HIV Drug) in HIV-Positive Women and to Compare Zidovudine Metabolism in Men and Women

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