Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women

NCT00869960 | Completed Phase 4 Results DMC

• 2 other identifiers: F0804280141K23AI074390-01A2
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Healthy Volunteers

Outcome Measures

Primary Outcomes (8)

• Tenofovir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses)

  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).

  between time of dosing to 24 hours after dose administered

• Tenofovir Systemic Exposure During the Luteal Phase (Days 20-25 After Menses)

  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).

  between time of dosing tp 24 hours after dose administration

• Emtricitabine Systemic Exposure During the Follicular Phase (Days 6-10 After Menses)

  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).

  Between time of dosing to 24 hours after dose administration

• Emtricitabine Systemic Exposure During the Luteal Phase (Days 20-25 After Menses)

  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).

  Between time of dosing to 24 hours after dose administration

• Atazanavir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses)

  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).

  Between time of dosing to 24 hours after dose administration

• Atazanavir Systemic Exposure During the Luteal Phase (Days 20-25 After Menses)

  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).

  Between time of dosing to 24 hours after dose administration

• Ritonavir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses)

  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).

  Between time of dosing to 24 hours after dose administration

• Ritonavir Systemic Exposure During the Luteal Phase (Days 20-25 After Menses)

  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).

  Between time of dosing to 24 hours after dose administration

Study Arms (1)

Antiretroviral therapy

EXPERIMENTAL

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; Drug: emtricitabine; Drug: atazanavir; Drug: ritonavir

Interventions

tenofovir DRUG

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)

Antiretroviral therapy

emtricitabine DRUG

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).

Antiretroviral therapy

atazanavir DRUG

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).

Antiretroviral therapy

ritonavir DRUG

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).

Antiretroviral therapy

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Interventions

Tenofovir; Emtricitabine; Atazanavir Sulfate; Ritonavir

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Azoles

Results Point of Contact

• Title: Jennifer King
• Organization: UAB

jenking@uab.edu

205-934-2696

Study Officials

• Jennifer R. King, PharmD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 26, 2009
• Study Start: March 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: September 6, 2013
• Results First Posted: April 12, 2012

Record last verified: 2013-08

Locations

US (1)