Levels of Raltegravir in the Female Genital Tissue

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01327482
Recruitment Status : Completed
First Posted : April 1, 2011
Results First Posted : December 19, 2014
Last Update Posted : December 19, 2014
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Caroline Mitchell, University of Washington

March 30, 2011
April 1, 2011
December 10, 2014
December 19, 2014
December 19, 2014
October 2011
December 2012   (Final data collection date for primary outcome measure)
Tissue Raltegravir Concentrations [ Time Frame: 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.
Tissue Raltegravir Concentrations [ Time Frame: 7, 14, 28 days ]
Complete list of historical versions of study NCT01327482 on Archive Site
Plasma Raltegravir Concentrations [ Time Frame: 7, 14, 21 days ]
Mean trough concentration from all 3 days
Plasma Raltegravir Concentrations [ Time Frame: 7, 14, and 28 days ]
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Levels of Raltegravir in the Female Genital Tissue
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

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.

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.

Not Applicable
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Drug: Raltegravir
Dosage: 400mg/PO (by mouth) Frequency: Twice daily Duration: During course of menstrual cycle (28 days)
Other Name: Isentress
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.
Intervention: Drug: Raltegravir
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
Not Provided
December 2012   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: Female
18 Years to 50 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
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Caroline Mitchell, University of Washington
University of Washington
Merck Sharp & Dohme Corp.
Principal Investigator: Caroline Mitchell, MD University Washington
Principal Investigator: Lisa Frenkel, MD Seattle Children's Research Institute
University of Washington
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP