Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women

Phase 4

Completed

Conditions: Healthy

Interventions: Drug: tenofovir
Drug: emtricitabine
Drug: atazanavir
Drug: ritonavir

Registration Number: NCT00869960

Lead Sponsor: University of Alabama at Birmingham

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 24

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Antiretroviral therapy	atazanavir	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.
Antiretroviral therapy	tenofovir	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.
Antiretroviral therapy	emtricitabine	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.
Antiretroviral therapy	ritonavir	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.

Primary Outcome Measures

Name	Time	Method
Tenofovir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses)	between time of dosing to 24 hours after dose administered	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)	between time of dosing tp 24 hours after dose administration	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)	Between time of dosing to 24 hours after dose administration	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)	Between time of dosing to 24 hours after dose administration	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)	Between time of dosing to 24 hours after dose administration	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)	Between time of dosing to 24 hours after dose administration	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)	Between time of dosing to 24 hours after dose administration	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)	Between time of dosing to 24 hours after dose administration	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).