- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01327482
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.
Aperçu de l'étude
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
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Washington
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Seattle, Washington, États-Unis, 98195
- University of Washington, Clinical Research Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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.
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Dosage: 400mg/PO (by mouth) Frequency: Twice daily Duration: During course of menstrual cycle (28 days)
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Tissue Raltegravir Concentrations
Délai: 7, 14, 21 days
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Mean trough concentration from all three days.
Tissue concentrations are measured from cervical biopsy homogenate using a mass-spectroscopy-based method.
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7, 14, 21 days
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Plasma Raltegravir Concentrations
Délai: 7, 14, 21 days
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Mean trough concentration from all 3 days
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7, 14, 21 days
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Caroline Mitchell, MD, University Washington
- Chercheur principal: Lisa Frenkel, MD, Seattle Children's Research Institute
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 38681-D
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