In Vivo Drug Interaction Pharmacokinetic Study of Tenofovir 1% Gel and Three Commonly Used Vaginal Products
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 101
- 试验地点
- 2
- 主要终点
- TFV concentrations in plasma and genital tissue and TFV-DP concentrations in genital tissue
研究概览
简要总结
The purpose of the study is determine if the local release characteristics and systemic exposure to tenofovir (TFV) 1% gel and a given commonly used vaginal product are impacted by concomitant use
详细描述
This study consists of three separate crossover studies, each evaluating if local release characteristics and systemic exposure to TFV 1% gel and a given vaginal product are impacted by concomitant use. Vaginal products to be assessed are: antifungal cream, antimicrobial gel, and the combination contraceptive vaginal ring (IVR). There will be no comparison between vaginal product groups.
Participants will be randomized to vaginal product. Participants in the cream and gel cohorts will be randomized to the order of treatment conditions (TFV gel alone, vaginal product alone, and TFV gel and vaginal product concomitantly). Participants in the IVR cohort will use TFV gel alone during the first crossover period; the order of the remaining treatment conditions (IVR alone, TFV and IVR concomitantly) for crossover periods 2 and 3 will be randomly assigned.
Each participant will attend a total of at least 7 visits. At the first visit, volunteers will be consented and will undergo procedures to assess whether they are eligible to continue in the study. If eligible, they will undergo 3 crossover treatment periods. Within each crossover treatment period there will be 2 visits, which will be scheduled to occur within the same menstrual cycle; the first visit will be in the follicular phase of the menstrual cycle such that product use is initiated on cycle day 9 to 18 and the second visit will be on cycle day 16 to 24.
At the start of crossover period 1, after it has been confirmed that the participant meets all of the inclusion criteria and none of the exclusion criteria, she will be randomized to a vaginal product cohort and to a sequence of the treatment conditions for the 3 crossover periods. Crossover periods 2 and 3 will be scheduled in the subsequent menstrual cycles, with the first visit of each crossover period occurring approximately 2 weeks after the completion of the previous crossover period.
Product usage during the 3 crossover periods is as follows:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age 18-50 years, inclusive
- •General good health (by volunteer history and per investigator discretion)
- •History of and currently regular menstrual cycles
- •Willing to abstain from the use of vaginal products, other than the TFV gel and her assigned study vaginal product for the duration of the study.
- •Willing to abstain from sex and other vaginal activity during each crossover period starting 72 hours prior to initiating product use, for the duration of use, and until the sixth day following sample collection
- •At low risk for pregnancy due to surgical sterilization of participant and/or her sexual partner, use of copper IUD or male condom, abstinence, or same sex relationship
- •Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself to easy genital tract sample collection
- •History of Pap smears and follow-up consistent with ACOG practice guidelines
- •Negative urine pregnancy test
- •Willing to give voluntary consent, sign an informed consent form and comply with study procedures as required by the protocol
排除标准
- •History of hysterectomy
- •Currently pregnant/within 2 calendar months from the last pregnancy outcome.
- •Use of Depo-Provera in the last 120 days or any hormonal contraceptives in the last month
- •Currently breastfeeding or having breastfed an infant in the last 2 months, or planning to breastfeed during the course of the study
- •History of sensitivity/allergy to any component of:
- •TFV 1% gel; or
- •topical anesthetic, or allergy to both silver nitrate and Monsel's solution.
- •Contraindication to any of 3 vaginal products (antifungal cream, antimicrobial gel, or the combination contraceptive vaginal ring) to which participants may be randomized
- •In the last 6 months, diagnosed with or treated for any STI or pelvic inflammatory disease, by self report.
- •Symptomatic BV
- •Positive test for Trichomonas vaginalis at Visit 1
- •Positive test for Neisseria gonorrhea or Chlamydia trachomatis
- •Positive test for HIV
- •Positive test for Hepatitis B surface antigen (HBsAg)
- •Known bleeding disorder that could lead to prolonged or continuous bleeding with biopsy
- •Chronic or acute vulvar or vaginal symptoms
- •Known current drug or alcohol abuse which could impact study compliance
- •Grade 2 or higher laboratory abnormality, per the August 2009 update of the DAIDS Table for Grading the Severity of Adverse Events
- •Systemic use in the last 2 weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and or clotting, antifungals, antivirals (e.g., acyclovir or valacyclovir) or antiretrovirals (e.g., Viread®).
- •Participation in any other drug or device interventional investigational trial (device, drug, or vaginal trial) within 30 days of this study or planned participation in any other investigational trial during the study
- •History of gynecological procedures (including genital piercing) on the external genitalia, vagina or cervix within the last 14 days
- •Abnormal finding on laboratory or physical examination or a social or medical condition which, in the opinion of the investigator, would make participation in the study unsafe or would complicate interpretation of data
研究组 & 干预措施
Tenofovir 1% gel
Participants will vaginally insert 1 applicator of TFV gel twice a day for 7 days, with each dose inserted approximately 12 hours after the previous dose (for a total of 13 doses). Each applicator contains 4.4 gm of TFV 1% gel.
干预措施: Tenofovir 1% gel (Drug)
Vaginal product alone
Participants will use their assigned vaginal product for 5 to 21 days depending on the dosing instructions for the particular product:
- Terconazole 0.4% vaginal cream: once a day for seven days. 1 applicator (5 gm) of terconazole cream contains 20 mg terconazole.
- Metronidazole gel: once a day for 5 days. 1 applicator (5 gm)of metronidazole gel contains 37.5 mg metronidazole.
- Contraceptive IVR: insert ring and leave in place for 21 days; return to clinic for removal on day 21. The IVR contains two active components, etonogestrel (progestin) and ethinyl estradiol (estrogen).
干预措施: Vaginal product (Drug)
Vaginal product and Tenofovir 1% gel
Tenofovir gel: Participants will vaginally insert 1 applicator of TFV gel twice a day for 7 days, with each dose inserted approximately 12 hours after the previous dose (for a total of 13 doses). Each applicator contains 4.4 gm of TFV 1% gel.
In addition, Participants will use their assigned vaginal product for 5 to 21 days depending on the dosing instructions for the particular product:
- Terconazole 0.4% vaginal cream: once a day for seven days. 1 applicator (5 gm) of terconazole cream contains 20 mg terconazole.
- Metronidazole gel: once a day for 5 days. 1 applicator (5 gm)of metronidazole gel contains 37.5 mg metronidazole.
- Contraceptive IVR: insert ring and leave in place for 21 days; return to clinic for removal on day 21. The IVR contains two active components, etonogestrel (progestin) and ethinyl estradiol (estrogen). Use of TFV gel will begin on day 15 of IVR use.
干预措施: Tenofovir 1% gel (Drug)
Vaginal product and Tenofovir 1% gel
Tenofovir gel: Participants will vaginally insert 1 applicator of TFV gel twice a day for 7 days, with each dose inserted approximately 12 hours after the previous dose (for a total of 13 doses). Each applicator contains 4.4 gm of TFV 1% gel.
In addition, Participants will use their assigned vaginal product for 5 to 21 days depending on the dosing instructions for the particular product:
- Terconazole 0.4% vaginal cream: once a day for seven days. 1 applicator (5 gm) of terconazole cream contains 20 mg terconazole.
- Metronidazole gel: once a day for 5 days. 1 applicator (5 gm)of metronidazole gel contains 37.5 mg metronidazole.
- Contraceptive IVR: insert ring and leave in place for 21 days; return to clinic for removal on day 21. The IVR contains two active components, etonogestrel (progestin) and ethinyl estradiol (estrogen). Use of TFV gel will begin on day 15 of IVR use.
干预措施: Vaginal product (Drug)
结局指标
主要结局
TFV concentrations in plasma and genital tissue and TFV-DP concentrations in genital tissue
时间窗: Assessments will be after product use (see description)
Vaginal product alone: Participant will use assigned product per dosing instructions (antifungal cream: 7 days; antimicrobial gel: 5 days; IVR: 21 days). In cream or gel cohorts, blood will be drawn 6 hrs after last use. In contraceptive ring cohort, blood will be drawn after 21 days of use at 0/4,6,10\&24 hrs. TFV gel alone: Participant will use TFV gel for 7 days, inserted 2X a day. In cream/gel cohorts blood will be drawn 4 hrs after last TFV gel use. In contraceptive ring cohort blood will be drawn 4,6,10\&24 hrs after last TFV gel use. Vaginal biopsy will occur 6 hrs after last TFV gel use for all. Vaginal product \& TFV gel: Participant will use assigned product per dosing instructions. TFV gel will be used for 7 days, 2X a day. In gel/cream cohorts blood will be drawn 4 hrs after last TFV gel use. In contraceptive ring cohort blood will be drawn 4,6,10\&24 hrs after last dose of TFV gel. Vaginal biopsy will occur 6 hrs after the last dose of TFV gel for all.
次要结局
- Vaginal product concentration in plasma(Assessments will be after product use (see description))
- Genitourinary adverse events (AEs)(Assessments will be after product use (see description))