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

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.

Condition or disease Intervention/treatment Phase
HIV Drug: Raltegravir Not Applicable

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : October 2011
Actual Primary Completion Date : December 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Plasma Raltegravir Concentrations [ Time Frame: 7, 14, 21 days ]
    Mean trough concentration from all 3 days

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01327482

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

Responsible Party: Caroline Mitchell, Assistant Professor, University of Washington Identifier: NCT01327482     History of Changes
Other Study ID Numbers: 38681-D
First Posted: April 1, 2011    Key Record Dates
Results First Posted: December 19, 2014
Last Update Posted: December 19, 2014
Last Verified: December 2014

Keywords provided by Caroline Mitchell, University of Washington:

Additional relevant MeSH terms:
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action