Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00869960

Enrollment

Registered

2009-03-26

Start date

2009-03-31

Completion date

2010-12-31

Last updated

2013-09-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Healthy Volunteers

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.

Interventions

DRUGtenofovir

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)

DRUGemtricitabine

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).

DRUGatazanavir

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).

DRUGritonavir

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).

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

21 Years to 40 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
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).

Countries

United States

Participant flow

Participants by arm

Arm	Count
Combination Antiretroviral Therapy Single dose administration of tenofovir, emtricitabine, atazanavir and ritonavir to healthy women	24
Total	24

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Lost to Follow-up	2

Baseline characteristics

Characteristic	Combination Antiretroviral Therapy
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	24 Participants
Age Continuous	27 years STANDARD_DEVIATION 5
Region of Enrollment United States	24 participants
Sex: Female, Male Female	24 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	0 / 24
serious Total, serious adverse events	0 / 24

Outcome results

Primary

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).

Time frame: Between time of dosing to 24 hours after dose administration