Levels of Raltegravir in the Female Genital Tissue

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01327482
• Other study ID #: 38681-D
• Status: Completed
• Phase: N/A
• First received: March 30, 2011
• Last updated: December 18, 2014
• Start date: October 2011

Study information

• Verified date: December 2014
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Raltegravir
Dosage: 400mg/PO (by mouth) Frequency: Twice daily Duration: During course of menstrual cycle (28 days)

Locations

Country	Name	City	State
United States	University of Washington, Clinical Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tissue Raltegravir Concentrations	Mean trough concentration from all three days. Tissue concentrations are measured from cervical biopsy homogenate using a mass-spectroscopy-based method.	7, 14, 21 days	No
Secondary	Plasma Raltegravir Concentrations	Mean trough concentration from all 3 days	7, 14, 21 days	No