Levels of Raltegravir in the Female Genital Tissue

Not Applicable

Completed

• Conditions: HIV
• Interventions: Drug: Raltegravir

• Registration Number: NCT01327482
• Lead Sponsor: University of Washington

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.

Study Timeline

• Study First Submitted: 2011-03-30
• Study First Submitted QC: 2011-03-31
• Study First Posted: 2011-04-01
• Study Start: 2011-10
• Primary Completion: 2012-12
• Status Verified: 2014-12
• Results First Submitted: 2014-12-10
• Results First Submitted QC: 2014-12-18
• Last Update Submitted: 2014-12-18
• Results First Posted: 2014-12-19
• Last Update Posted: 2014-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All	Raltegravir	All patients were part of the intervention arm, as this was a pharmacokinetic study. All women took Raltegravir 400mg orally, twice daily for 3 weeks.

Primary Outcome Measures

Name	Time	Method
Tissue Raltegravir Concentrations	7, 14, 21 days	Mean trough concentration from all three days. Tissue concentrations are measured from cervical biopsy homogenate using a mass-spectroscopy-based method.

Secondary Outcome Measures

Name	Time	Method
Plasma Raltegravir Concentrations	7, 14, 21 days	Mean trough concentration from all 3 days

Trial Locations

Locations (1)

University of Washington, Clinical Research Center; 🇺🇸 Seattle, Washington, United States