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Levels of Raltegravir in the Female Genital Tissue

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Caroline Mitchell, University of Washington
ClinicalTrials.gov Identifier:
NCT01327482
First received: March 30, 2011
Last updated: December 18, 2014
Last verified: December 2014
History of Changes
  Purpose

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.

Condition Intervention
HIV
 Drug: Raltegravir

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Tissue Raltegravir Concentrations [ Time Frame: 7, 14, 21 days ] [ Designated as safety issue: No ]
    Mean trough concentration from all three days. Tissue concentrations are measured from cervical biopsy homogenate using a mass-spectroscopy-based method.


Secondary Outcome Measures:
  • Plasma Raltegravir Concentrations [ Time Frame: 7, 14, 21 days ] [ Designated as safety issue: No ]
    Mean trough concentration from all 3 days
Enrollment: 10
Study Start Date: October 2011
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All
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.
 Drug: Raltegravir
Dosage: 400mg/PO (by mouth) Frequency: Twice daily Duration: During course of menstrual cycle (28 days)
Other Name: Isentress

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
Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01327482

Locations
United States, Washington
University of Washington, Clinical Research Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Caroline Mitchell, MD University Washington
Principal Investigator: Lisa Frenkel, MD Seattle Children's Research Institute
  More Information

No publications provided

Responsible Party: Caroline Mitchell, Assistant Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01327482     History of Changes
Other Study ID Numbers: 38681-D
Study First Received: March 30, 2011
Results First Received: December 10, 2014
Last Updated: December 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Washington:
Raltegravir
Pharmacokinetics

ClinicalTrials.gov processed this record on February 27, 2015