Clinical trial NCT01327482: Levels of Raltegravir in the Female Genital Tissue
Official title: Modeling Intracellular and Extracellular Raltegravir (RAL) Pharmacokinetics in the Female Genital Tract and Blood After a Twice Daily 400mg Dose Over the Course of a Menstrual Cycle
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: Raltegravir
Pharmacokinetics
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-04-01
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: This study is an investigation of the pharmacokinetics of raltegravir in the tissue of the female genital tract to determine if twice-daily dosing of 400mg achieves adequate drug levels to prevent viral integration of HIV-1. The study will also assess whether drug levels change in the tissue across the different phases of the menstrual cycle.

* Hypothesis #1: Twice daily dosing with raltegravir 400mg will result in intracellular concentrations that should be sufficient to suppress HIV-1 replication throughout the menstrual cycle.
* Hypothesis #2: Intracellular genital raltegravir peaks will be lower and troughs higher compared to extracellular concentrations in the plasma and PMBCs (peripheral blood mononuclear cells).
* Hypothesis #3: Intracellular raltegravir concentrations will be slightly lower during the luteal phase of the menstrual cycle due to cellular pumps such as p-glycoprotein, which are present in higher numbers during periods of high progesterone.

Detailed description: HIV-1 is shed in genital secretions which increase the risk of transmission between sexual partners and from mother to infant. Antiretroviral medication taken prior to exposure to HIV-1 can prevent viral transmission from a mother to her infant. Raltegravir (RAL), by blocking integration of viral cDNA into the host's genome, makes an excellent candidate for preventing HIV-1 infection. RAL is licensed for treatment with twice-daily dosing based on plasma trough concentrations; however, intracellular concentrations of RAL which are relevant to blocking infection of cells have not been previously studied. P-glycoprotein pumps, which are involved in regulating drug absorption and metabolism, can influence intracellular drug concentrations. P-glycoprotein concentrations appear to vary with menstrual cycle suggesting it may affect intracellular drug concentration of RAL in women.

Women will be enrolled in the study and followed during the course of a menstrual cycle while taking a dose of 400mg PO twice daily. An initial screening visit will be performed prior to enrollment and participation in the study. Review of medical history as well as blood and urine collection will occur during the screening visit. Once enrolled, participants will have blood and genital tract samples collected once a week for four weeks to assess intracellular concentrations of RAL in the blood and genital tract tissue.

Eligibility criteria: Inclusion Criteria

Volunteers must be:

* Over 18 years of age.
* Willing to abstain from sexual intercourse during course of study.
* Able to commit to follow-up visit schedule.
* Willing to abstain from use of vaginal medications or creams 48 hours prior to follow-up visits.
* Willing and able to provide informed consent.

Exclusion Criteria

Volunteers will not be eligible for the study if they:

* Are over 50 years of age.
* Are pregnant, attempting to become pregnant, or breast-feeding.
* Have irregular menstrual bleeding.
* Are using a hormonal form of birth control.
* Have abnormal liver/kidney function test results at screening visit.
* Have HIV-positive test result at screening visit.

Primary outcomes:
measure: Tissue Raltegravir Concentrations
timeFrame: 7, 14, 21 days
Secondary outcomes:
measure: Plasma Raltegravir Concentrations
timeFrame: 7, 14, 21 days
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington, Clinical Research Center
state: Washington
Study officials:
affiliation: University Washington
name: Caroline Mitchell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Lisa Frenkel, MD
role: PRINCIPAL_INVESTIGATOR
References: