A Prospective, Randomized, Three-period Crossover, Interaction Study to Evaluate the Pharmacokinetics of Doravirine and Tenofovir Disoproxil Fumarate Co-administered With Cross-sex Hormonal Therapy in Adult HIV-negative Transgender Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)
研究概览
简要总结
Transgender women living with Human Immunodeficiency Virus (HIV) may prioritize gender-affirming hormonal therapy over antiretroviral drug therapy. Hormonal therapy typically consists of oral estradiol and spironolactone, which induce drug-metabolizing enzymes after prolonged administration. This study evaluates the bi-directional potential drug interaction between the antiretroviral drug, doravirine, when co-administered with estradiol and spironolactone.
详细描述
This study will consist of healthy transgender women volunteers randomized to a 1:1 sequence ("E" or "F") There are three periods and in each period there are one of three treatments
Treatment A: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate alone Treatment B: Single-dose estradiol and spironolactone co-administered with placebo Treatment C: Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone
The primary outcome measures are the drug concentrations
The primary comparisons are geometric mean ratios of drugs with potential perpetrators of drug interactions using a crossover method
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy self-identified transgender women (male-to-female) between 18-45 years old at the time of screening
- •Have not undergone an orchiectomy
- •Receiving oral estradiol and spironolactone for >/= 3 months prior to study entry with a self-reported adherence to prescribed doses of >/= 90%
- •Agree to abstain from alcohol consumption throughout the duration of the study
- •Be willing to briefly interrupt hormonal therapy prior to and during the study
- •If on pre-exposure prophylaxis (PrEP) therapy containing tenofovir alafenamide or tenofovir disoproxil fumarate, willing to discontinue PrEP at least 2 weeks before study start and for the duration of the study
- •Agree to use condoms for all sexual activity prior to the start and throughout the duration of the study
- •Evidence of a personal signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study
排除标准
- •Presence of clinically significant acute or chronic disease, that in the investigator's opinion, would compromise the participant's safety during the study
- •Use of injectable or transdermal estradiol
- •Use of any other hormonal replacement therapy, wit h the exception of oral estradiol and spironolactone
- •Current use of any antiretroviral drug. This will not be exclusionary if participants reported discontinuing within 30 days of screening
- •Creatinine clearance </= 60 mL/min, as estimated by the Cockcroft-Gault equation
- •Known anaphylactic or severe systemic reactions to any components of doravirine, lamivudine, or tenofovir disoproxil fumarate
- •Positive HIV, hepatitis B or Hepatitis C virus at screening. Evidence of prior hepatitis B infection and immunity is not exclusionary. Positive hepatitis C antibody with negative viral load or documented antiviral hepatitis C treatment with one post treatment non-detectable hepatitis C viral load is not exclusionary
- •Recent significant blood or plasma donation
研究组 & 干预措施
Treatment A
Single-dose oral Doravirine/lamivudine/tenofovir disoproxil
干预措施: Doravirine/Lamivudine/Tenofovir (Drug)
Treatment B
Single-dose estradiol and spironolactone co-administered with placebo
干预措施: Spironolactone 100mg (Drug)
Treatment B
Single-dose estradiol and spironolactone co-administered with placebo
干预措施: Estradiol 2mg (Drug)
Treatment B
Single-dose estradiol and spironolactone co-administered with placebo
干预措施: Placebo (Other)
Treatment C
Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone
干预措施: Doravirine/Lamivudine/Tenofovir (Drug)
Treatment C
Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone
干预措施: Spironolactone 100mg (Drug)
Treatment C
Single-dose oral Doravirine/lamivudine/tenofovir disoproxil fumarate co-administered with estradiol and spironolactone
干预措施: Estradiol 2mg (Drug)
结局指标
主要结局
Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)
时间窗: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Doravirine AUC derived from plasma sampling with geometric mean ratio compared between treatment arms
Doravirine Maximum Concentration (Cmax)
时间窗: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Doravirine maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms
Doravirine Trough Concentration (C24)
时间窗: 24 hours post-dose for all participants
Doravirine observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms
Tenofovir Disoproxil Fumarate Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)
时间窗: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Tenofovir AUC derived from plasma sampling with geometric mean ratio compared between treatment arms
Tenofovir Disoproxil Fumarate Maximum Concentration (Cmax)
时间窗: Pre-dose, 0.5, 1, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Tenofovir maximum observed concentration during the dosing interval
Tenofovir Disoproxil Fumarate Trough Concentration (C24)
时间窗: 24 hours post-dose for all participants
Tenofovir observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms
Estradiol Area Under the Plasma Concentration Versus Time Curve From 0 Hours to Infinity (AUC0-∞)
时间窗: Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Estradiol area under the plasma concentration versus time curve from 0 hours to infinity (AUC) derived from plasma sampling
Estradiol Maximum Concentration (Cmax)
时间窗: Pre-dose, 0.5, 2, 6, 12, 24, 48, 72, 96 hours post-dose for all participants
Estradiol maximum observed concentration during the dosing interval with geometric mean ratio compared between treatment arms
Estradiol Trough Concentration (C12)
时间窗: 12 hours post-dose for all participants
Estradiol observed trough concentration during the dosing interval with geometric mean ratio compared between treatment arms
次要结局
未报告次要终点
研究者
Walter K. Kraft
Principal Investigator
Thomas Jefferson University