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Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00869960
First received: March 25, 2009
Last updated: August 17, 2013
Last verified: August 2013
  Purpose

Data suggest that women taking drugs to treat human immunodeficiency virus (HIV) have higher amounts of drugs in their body compared with men taking the same dose of anti-HIV drugs. The reason for this higher drug exposure has not been determined. The primary purpose of this study is to examine whether the pharmacokinetics (factors that determine the amount of drug in the body) of anti-HIV drugs change during different phases of the menstrual cycle in women and ultimately result in higher amounts of drug in the body compared with men. In other words, we plan to examine whether changes in sex hormones throughout the menstrual cycle affect the amount of anti-HIV drugs in women. The antiretroviral drugs atazanavir, ritonavir, tenofovir and emtricitabine will be studied. This study will be conducted in healthy women since HIV may change the pharmacokinetics of anti-HIV drugs.


Condition Intervention Phase
Healthy
Drug: tenofovir
Drug: emtricitabine
Drug: atazanavir
Drug: ritonavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Tenofovir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses) [ Time Frame: between time of dosing to 24 hours after dose administered ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Follicular phase starts on day 1 of the menstrual cycle when estrogen and progesterone levels are lowest. this lasts 14 days. Dose administration and PK would have been drawn on day 6, 7, 8, 9, or 10 after Day 1 (start of Follicular phase).

  • Tenofovir Systemic Exposure During the Luteal Phase (Days 20-25 After Menses) [ Time Frame: between time of dosing tp 24 hours after dose administration ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Luteal phase starts on day 14 of the menstrual cycle when estrogen and progesterone levels are beginning to increase. This lasts 14 days or until Day 1 of the Follicular phase. Dose administration and PK during the Luteal phase, would have been drawn on day 20, 21, 22, 23, 24 and 25 start of Follicular phase).

  • Emtricitabine Systemic Exposure During the Follicular Phase (Days 6-10 After Menses) [ Time Frame: Between time of dosing to 24 hours after dose administration ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Follicular phase starts on day 1 of the menstrual cycle when estrogen and progesterone levels are lowest. this lasts 14 days. Dose administration and PK would have been drawn on day 6, 7, 8, 9, or 10 after Day 1 (start of Follicular phase).

  • Emtricitabine Systemic Exposure During the Luteal Phase (Days 20-25 After Menses) [ Time Frame: Between time of dosing to 24 hours after dose administration ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Luteal phase starts on day 14 of the menstrual cycle when estrogen and progesterone levels are beginning to increase. This lasts 14 days or until Day 1 of the Follicular phase. Dose administration and PK during the Luteal phase, would have been drawn on day 20, 21, 22, 23, 24 and 25 start of Follicular phase).

  • Atazanavir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses) [ Time Frame: Between time of dosing to 24 hours after dose administration ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Follicular phase starts on day 1 of the menstrual cycle when estrogen and progesterone levels are lowest. this lasts 14 days. Dose administration and PK would have been drawn on day 6, 7, 8, 9, or 10 after Day 1 (start of Follicular phase).

  • Atazanavir Systemic Exposure During the Luteal Phase (Days 20-25 After Menses) [ Time Frame: Between time of dosing to 24 hours after dose administration ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Luteal phase starts on day 14 of the menstrual cycle when estrogen and progesterone levels are beginning to increase. This lasts 14 days or until Day 1 of the Follicular phase. Dose administration and PK during the Luteal phase, would have been drawn on day 20, 21, 22, 23, 24 and 25 start of Follicular phase).

  • Ritonavir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses) [ Time Frame: Between time of dosing to 24 hours after dose administration ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Follicular phase starts on day 1 of the menstrual cycle when estrogen and progesterone levels are lowest. this lasts 14 days. Dose administration and PK would have been drawn on day 6, 7, 8, 9, or 10 after Day 1 (start of Follicular phase).

  • Ritonavir Systemic Exposure During the Luteal Phase (Days 20-25 After Menses) [ Time Frame: Between time of dosing to 24 hours after dose administration ] [ Designated as safety issue: No ]
    Systemic exposure determined by area under the concentration time curve was measured by blood drawn for PK assessment at the following times: 0 (time of dose), 0.5, 1, 2, 4,6, 8, 12 and 24 hours. The Luteal phase starts on day 14 of the menstrual cycle when estrogen and progesterone levels are beginning to increase. This lasts 14 days or until Day 1 of the Follicular phase. Dose administration and PK during the Luteal phase, would have been drawn on day 20, 21, 22, 23, 24 and 25 start of Follicular phase).


Enrollment: 24
Study Start Date: March 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Antiretroviral therapy
Healthy volunteers received two doses of Tenofovir, Emtricitabine, Atazanavir and Ritonavir administered twice (on day 6 - 10 and day 20 - 25 after day of Follicular phase); with pharmacokinetic measurements at 6 - 10 days after menses and then again at day 20 - 25 after menses.
Drug: tenofovir
tenofovir 300 mg one dose on 2 separate visits: within 5 days after Day 1 of Follicular phase and then within a 4 day window of the leutal phase (day 14 of the menstrual cycle)
Drug: emtricitabine
emtricitabine 200 mg on 2 separate visits: within 5 days after Day 1 of Follicular phase and then within a 4 day window of the leutal phase (day 14 of the menstrual cycle).
Drug: atazanavir
atazanavir 300mg one dose on 2 separate visits: within 5 days after Day 1 of Follicular phase and then within a 4 day window of the leutal phase (day 14 of the menstrual cycle).
Drug: ritonavir
ritonavir 100 mg one dose on 2 separate visits: within 5 days after Day 1 of Follicular phase and then within a 4 day window of the leutal phase (day 14 of the menstrual cycle).

  Eligibility

Ages Eligible for Study:   21 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy, HIV negative, nonsmoking females between 21 and 40 years of age.
  • Subjects must be within 20% of their ideal body weight and have a regular menstrual cycle, defined as at least 10 cycles per year occurring approximately every 28 ± 4 days and cycle length varying by not more than 7 days.
  • Subjects must be willing and able to provide written informed consent.
  • Subjects cannot be breast feeding, pregnant or be taking hormonal contraception within 3 months prior to study enrollment. However, they must agree to use an effective non-hormonal method of contraception during the study.

Exclusion Criteria:

  • Subjects receiving prescription or over-the-counter products which may interact with the study medication will be excluded from the study.
  • Subjects with a Grade 3 or higher laboratory liver, renal or hematology abnormality as specified below in accordance with the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 1.0, Dec 2004, will be excluded.
  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: NCT00869960

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Jennifer R. King, PharmD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00869960     History of Changes
Other Study ID Numbers: F080428014, 1K23AI074390-01A2
Study First Received: March 25, 2009
Results First Received: March 15, 2012
Last Updated: August 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Healthy Volunteers

Additional relevant MeSH terms:
Atazanavir
Emtricitabine
Ritonavir
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014