Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

Dose Proportionality of TFV-DP After a Single Dose of GS-7340 in Women

29. November 2016 aktualisiert von: University of North Carolina, Chapel Hill

Dose Proportionality of TFV-DP in Mucosal Tissue, and Endogenous Nucleotide Quantification, After a Single Dose of GS-7340 in Women

Purpose:

The purpose of this study is to characterize the dose-proportionality in the distribution of tenofovir alafenamide (TAF) and tenofovir (TFV) in plasma and mucosal tissues, and TFV-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) and mucosal tissues of healthy female subjects following a single oral dose of GS-7430 at 5mg, 10mg, and 25mg.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

Participants:

This study will consist of approximately 24 premenopausal healthy volunteer women between 18-49 years of age with an intact cervix, uterus, and gastrointestinal tract. Women will be enrolled in the study within 42 days of screening depending on the timing of their menstrual cycle in comparison to the screening visit, and then will be on study for 14 days, with follow-up 1-14 days after the end of study sampling. All study visits will be conducted in the North Carolina Translational and Clinical Sciences (NCTraCS) Clinical Translational Research Center (CTRC) at the University of North Carolina at Chapel Hill.

Procedures (methods):This is a Phase 1, single center, open-label, dose-ranging pharmacokinetic study of TFV and TFV-DP mucosal tissue concentrations measured after a single dose of GS-7340. Each arm is divided into three dosing groups: 5, 10, or 25mg. Participants will take a single dose of study drug within 7-14 days following the end of the subjects' menstrual period. Participants will be sequentially assigned to one of the three TAF doses and four biopsy schedules. Two women from each of the dosing groups will be assigned to one of four biopsy schedules for a total of 8 women per dosing group. Samples of blood plasma, cervicovaginal fluid (CVF), cervical tissue, vaginal tissue, and rectal tissue will be collected from participants at varying time points over the 14 days post-dose. Subjects will return to clinic within 14 days after the last sampling to complete a follow-up safety visit.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

24

Phase

  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

    • North Carolina
      • Chapel Hill, North Carolina, Vereinigte Staaten, 27599
        • University of North Carolina at Chapel Hill

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 49 Jahre (Erwachsene)

Akzeptiert gesunde Freiwillige

Ja

Studienberechtigte Geschlechter

Weiblich

Beschreibung

Inclusion Criteria

  1. Healthy pre-menopausal female subjects between the ages of 18 and 49 years, inclusive on the date of screening, with an intact gastrointestinal tract, uterus, and cervix.
  2. All subjects must have an estimated calculated creatinine clearance (eCcr) of at least 80 mL/min
  3. All subjects must have negative pregnancy tests, and be using an acceptable form of birth control
  4. Body Mass Index (BMI) of approximately 18 to 34 kg/m²; and a total body weight > 45 kg (99 lbs).
  5. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
  6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
  7. Subject must have documentation of a normal pap smear within 36 months of the screening visit, no procedures for abnormal cervical/vaginal pathology in the last six months, at least one prior gynecological visit as part of subject's routine medical history.
  8. Subject must be willing to abstain from sexual intercourse, douching, and all intravaginal and intrarectal objects and products for at least 72 hours prior to Day 1 until study completion.
  9. Subject must be HIV-1 and Hepatitis B surface antigen negative
  10. Subject must not be actively involved in the conception process.
  11. Subject must be able to swallow pills and have no allergies to any component of the study products

Exclusion Criteria

  1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
  2. Subjects with a history of hysterectomy
  3. Subjects who are pregnant, possibly pregnant or lactating
  4. Subjects with a presence of vaginal discharge or genital bleeding at screening
  5. History of febrile illness within five days prior to first dose.
  6. Any condition possibly affecting drug absorption (eg, gastrectomy).
  7. A positive urine drug screen.
  8. A positive result for HIV, Hepatitis B or C
  9. An untreated-positive test for syphilis, gonorrhea, Chlamydia, or trichomonas at screening, or symptomatic bacterial vaginosis.
  10. Any laboratory chemistry or hematology result Grade 2 or greater according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) Laboratory Grading Tables
  11. Treatment with an investigational drug within 4 months preceding the first dose of trial medication.
  12. History of regular alcohol consumption exceeding study limits
  13. Participation in a clinical trial involving vaginal or rectal biopsies within 6 months preceding the first dose of trial medication.
  14. Use of prescription or nonprescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of trial medication and unable to avoid use during the study period until after the last sample is collected.
  15. Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
  16. History of sensitivity to heparin or heparin-induced thrombocytopenia.
  17. Allergy to lidocaine or Monsel's solution.
  18. Allergy to latex.
  19. Abnormal pap smear in the past 36 months
  20. Any degree of ectopy or abnormality evident during the pelvic exam at screening.
  21. Any condition which, in the opinion of the investigator, is likely to interfere with follow-up or ability to take the study medication appropriately.
  22. Unwilling or unable to comply with the dietary and concomitant drug restrictions in regard to study drug administration as outlined in the study procedures and prohibited medications sections.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Verhütung
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 1. GS-7340 25mg
The first 8 women on study will be assigned to take a single dose of 25mg TAF (1 tablet) orally.
Medication is supplied in 10 or 25mg tablets, so subjects will receive either 1/2 or one tablet in a single dose.
Andere Namen:
  • TAF
  • Tenofovir Alafenamide
Experimental: 2. GS-7340 10mg
The 2nd group of 8 women will be sequentially assigned to take a single dose of 10mg TAF (1 tablet) orally.
Medication is supplied in 10 or 25mg tablets, so subjects will receive either 1/2 or one tablet in a single dose.
Andere Namen:
  • TAF
  • Tenofovir Alafenamide
Experimental: 3. GS-7340 5mg
The final 8 women on study will be sequentially assigned to take a single dose of 5mg TAF (1/2 tablet) orally.
Medication is supplied in 10 or 25mg tablets, so subjects will receive either 1/2 or one tablet in a single dose.
Andere Namen:
  • TAF
  • Tenofovir Alafenamide

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Plasma Dose-Proportionality
Zeitfenster: Pre-dose and 1, 3, 6, 12, 24 hours, and 3, 7, 10, and 14 days following single dose
To characterize the dose-proportionality in the distribution of TAF and TFV in the plasma of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
Pre-dose and 1, 3, 6, 12, 24 hours, and 3, 7, 10, and 14 days following single dose
Tissue Dose-Proportionality
Zeitfenster: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
To characterize the dose-proportionality in the distribution of TAF and TFV in mucosal tissues, and TFV-DP in mucosal tissues of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
PBMC Dose-Proportionality
Zeitfenster: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
To characterize the dose-proportionality in the distribution of TFV-DP in PBMCs of healthy female subjects following a single oral dose of GS-7340 at 5mg, 10mg, and 25mg. This will be used to develop a predictive pharmacokinetic model for TAF which will allow for TFVdp exposure predictions given a specific dose and dosing interval.
Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Intra-subject variability in intracellular deoxyadenosine triphosphate (dATP) in peripheral blood
Zeitfenster: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
To determine intra-subject variability in intracellular dATP in PBMCs and ratios of TFVdp:dATP.
Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
Inter-subject variability in intracellular deoxyadenosine triphosphate (dATP) in peripheral blood
Zeitfenster: Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
To determine inter-subject variability in intracellular dATP in PBMCs and ratios of TFVdp:dATP.
Pre-dose and 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose
Intra-subject variability in intracellular deoxyadenosine triphosphate (dATP) in mucosal tissues
Zeitfenster: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
To determine intra-subject variability in intracellular dATP in cervical, vaginal, and rectal tissues and ratios of TFVdp:dATP.
At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
Inter-subject variability in intracellular deoxyadenosine triphosphate (dATP) in mucosal tissues
Zeitfenster: At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose
To determine inter-subject variability in intracellular dATP in cervical, vaginal, and rectal tissues and ratios of TFVdp:dATP.
At 3, 6, 12 and 24 hours and 3, 7, 10 and 14 days following single dose

Andere Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Cervicovaginal Fluid (CVF) Concentration
Zeitfenster: At 1, 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose.
To determine if TFV and TAF concentration in CVF changes in proportion to TFV, TAF, and TFV-DP concentration in cervical and vaginal tissue
At 1, 3, 6, 12, 24 hours and 3, 7, 10, and 14 days following single dose.

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Mitarbeiter

Ermittler

  • Hauptermittler: Angela DM Kashuba, PharmD, UNC Chapel Hill

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. März 2015

Primärer Abschluss (Tatsächlich)

1. Oktober 2015

Studienabschluss (Tatsächlich)

1. November 2016

Studienanmeldedaten

Zuerst eingereicht

14. Januar 2015

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

2. Februar 2015

Zuerst gepostet (Schätzen)

6. Februar 2015

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Schätzen)

30. November 2016

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

29. November 2016

Zuletzt verifiziert

1. November 2016

Mehr Informationen

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Abonnieren