A Phase I Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of a Vaginal Insert Containing Tenofovir Alafenamide and Elvitegravir
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
The purpose of this Phase I study is to assess the safety, pharmacokinetics, and pharmacodynamics of a combination vaginal insert containing tenofovir alafenamide (TAF) and elvitegravir (EVG).
This study will be the first-in-human study for a vaginally administered TAF/EVG insert and will evaluate safety, PK and PD after a single dose. It is hypothesized that the combination insert will be safe and well-tolerated by study participants and that the insert will offer an expanded window of preventive activity and a regimen with flexibility and forgiveness.
详细描述
This Phase I study aims to complete at least 16 healthy, non-pregnant, HIV-uninfected women aged 18-50 years who are not at risk for pregnancy and are at low risk for sexually transmitted infections (STIs) at one clinical site. The study will examine the safety, PK, PD, disintegration, and acceptability of vaginal inserts containing the combination of tenofovir alafenamide (TAF) and elvitegravir (EVG).
Participants will be randomized (1:1) into one of two sample collection time point groups:
[Timepoint group 1: 4 and 48 hours after using the single combination insert] or [Timepoint group 2: 24 and 72 hours after using the single combination insert]
There will be 5 scheduled visits:
Visit 1 (Screening/Enrollment): Volunteers will be consented and undergo tests and procedures to confirm they are eligible to continue in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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 to 50 years, inclusive
- •General good health (by volunteer history and per investigator judgment) without any clinically significant systemic disease (including, but not limited to significant liver disease/hepatitis, gastrointestinal disease, kidney disease, thyroid disease, bone disease, and diabetes) and with an intact uterus and cervix.
- •History of regular menstrual cycles, by volunteer report (for cycling women)
- •History of Pap smears and follow-up consistent with standard clinical practice as outlined in the Study Manual or willing to undergo a Pap smear at Visit 1
- •Able to communicate in spoken and written English
- •Willing to give voluntary consent and sign an informed consent form
- •Willing and able to comply with protocol requirements, including abstaining from vaginal activity and product use at specified times
- •Must be protected from pregnancy by one of the following:
- •Hormonal methods, except vaginal rings and DMPA
- •Copper IUD
- •Sterilization of participant or partner
- •Consistent condom use
- •Abstinence from penile-vaginal intercourse
- •Same sex relationship
- •If in a relationship, must be in a mutually monogamous relationship with a partner who is not known to be HIV positive and has no known risk of sexually transmitted infections (STIs)
排除标准
- •Positive pregnancy test or plans to become pregnant during the course of the study
- •Currently breastfeeding or planning to breastfeed during the course of the study
- •History of sensitivity/allergy to any component of the study product, topical anesthetic, or to both silver nitrate and Monsel's solution
- •In the last three months, diagnosed with or treated for any STI (For HSV, ideally no outbreaks in the past year. More than two outbreaks in previous 12 month period is exclusionary.)
- •Positive test for Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis (CT), HIV, or Hepatitis B surface antigen (HBsAg)
- •Symptomatic bacterial vaginosis (BV)
- •Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting/bleeding, discharge, etc.)
- •Known blood disorder, including deep vein thrombosis (DVT) and pulmonary embolism (PE), or those that could lead to prolonged or continuous bleeding with biopsy
- •NSAIDS, systemic corticosteroids (e.g. dexamethasone), Endothelin Receptor Antagonists (e.g bosentan), antibiotics, Anticonvulsants (e.g. carbamazepine, oxcarbazepine, phenobarbital, phenytoin), Antimycobacterials (Rifbutin, Rifampin, Rifapentine) anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals (i.e ketoconazole), or antivirals or antiretroviral (e.g. acyclovir, valacyclovir, Viread®, Atripla®, Emtriva®, or Complera®), St. John's Wort or drugs that may interact with TAF or EVG as specified in the Vitekta and Vemlidy Investigator Brochure, should not be used during the study.
- •Current or anticipated chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetominophen for the duration of the study.
- •Participation in any other investigational trial with use of a drug/device within the last 30 days or planned participation in any other investigational trial with use of a drug/device during the study
- •Grade 2 or higher laboratory abnormality, per the Division of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for Grading the Severity of Adverse Events, or clinically significant laboratory abnormality as determined by the clinician
- •Abnormal finding on laboratory or physical examination or a social or medical condition in the volunteer 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
TAF/EVG vaginal insert
Post-dose sampling at 4 and 48 hours or at 24 and 72 hours, per randomization
干预措施: TAF/EVG Vaginal Insert (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: Changes from baseline up to a maximum of 12 days post-dose
Adverse events for this outcome are those that are product-related urogenital in nature
systemic laboratory assessments
时间窗: Changes from baseline up to 72 hours post-dose
Number of participants with abnormal serum chemistry
Systemic Laboratory Assessments
时间窗: Changes from baseline up to 72 hours post-dose
Number of participants with abnormal complete blood count
Drug Concentrations of EVG, TFV, and TAF
时间窗: From dosing to a maximum of 12 days post-dose
Concentrations of EVG, TFV, and TAF in CV fluid
Number of Participants with Grade 2 or higher treatment-emergent adverse events (TEAEs)
时间窗: Changes from baseline up to a maximum of 12 days post-dose
TEAEs are defined as adverse events starting or worsening after administration of the study product; Grade is determined by the DAIDS Grading Table
Drug Concentrations of EVG, TFV, TFV-DP, and TAF
时间窗: From dosing to 72 hours post-dose
Concentrations of EVG, TFV, TFV-DP, TAF in CV tissue
次要结局
- Percent (%) inhibition of HIV in vaginal cell assay (Anti-HIV activity)(Changes from baseline to 24 hours post-dose)
- Percent (%) inhibition of HSV in vaginal cell assay (Anti-HSV activity)(Changes from baseline to 24 hours post-dose)
- Number of participant tissue samples demonstrating HIV-1 infectivity(Changes from baseline to 4 hours post-dose)
- Disintegration of insert(At 4 or 24 hours post-dose (per randomized time point))
- Acceptability of insert: questionnaire(At baseline and at 48 or 72 hours post-dose (per randomized time point))