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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

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000897
First received: November 2, 1999
Last updated: March 1, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention
HIV Infections
Drug: Zidovudine

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: The Effect of Oral and Injectable Contraceptives (Norethindrone/Ethinyl Estradiol, Medroxyprogesterone Acetate) and Gender on Plasma and Intracellular Zidovudine Pharmacokinetics

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 42
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000897

Locations
United States, California
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, Florida
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, United States, 32209
United States, New York
Children's Hosp at Albany Med Ctr
Albany, New York, United States, 12208
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Francesca Aweeka
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00000897     History of Changes
Other Study ID Numbers: ACTG 317, AACTG 317
Study First Received: November 2, 1999
Last Updated: March 1, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Interactions
Zidovudine
Sex Factors
Reverse Transcriptase Inhibitors
Contraceptives, Oral
Progestational Hormones, Synthetic
Anti-HIV Agents
Viral Load
Estrogens

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Zidovudine
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Contraceptive Agents
Medroxyprogesterone Acetate
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antiviral Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents

ClinicalTrials.gov processed this record on November 25, 2014