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

• Status: Completed
• Trial end date: 2016-11-01
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Gilead Sciences
• Treatments: Tenofovir

Criteria

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.