Bioequivalence of Crushed and Whole Genvoya Tablets (Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- AUC0-∞ for FTC
研究概览
简要总结
Step-wise, two sequential, single-dose, bioequivalence study in 12 healthy volunteers to determine whether crushed Genvoya tablet is bioequivalent to whole Genvoya tablet. The first study sequence will involve a directly observed single dose of the fixed dose formulation of whole Genvoya tablet, with semi-intensive pharmacokinetic serum sampling at time points following the dose. After a washout period of seven days, subjects will then receive a directly observed single dose of a crushed tablet of Genvoya with subsequent semi-intensive pharmacokinetic serum sampling.
详细描述
Genvoya, a fixed-dose combination of the two Nucleoside Reverse Transcriptase Inhibitors (NRTI) emtricitabine (FTC) 200mg and tenofovir alafenamide (TAF) 10mg, with the integrase inhibitor elvitegravir (EVG) and the boosting agent cobicistat (COBI), is FDA approved for the treatment of HIV-infected patients.
Despite the availability of Genvoya allowing for a single tablet fixed-dose combination and once-daily dosing, a substantial number of individuals living with HIV suffer from pill aversion, dysphagia, odynophagia, or problems swallowing oral regimens, all of which can contribute to non-adherence. These observations are especially important because non-adherence to antiretroviral (ARV) medications is highly prevalent and associated with decreased survival. Non-adherence has been estimated at 55% in North American pooled cohorts, and is a vital public health concern, as it leads to treatment failure and transmission of drug-resistant virus.
Many clinical scenarios make the administration of crushed tablets desirable as a potential strategy to overcome pill aversion. However, there is a theoretical concern that the systemic absorption of the active ingredients of tablets may be altered by crushing the pills. In fact, pharmacokinetic and bioequivalence data are lacking for most antiretroviral fixed-dose combinations used in the treatment of HIV-infected patients. It is therefore of substantial practical and clinical interest to know whether antiretroviral combinations such as Genvoya can be taken in crushed form with bioequivalence to whole tablet form.
This is a step-wise bioequivalence single-dose and two sequential design study in healthy volunteers to evaluate the combination Genvoya to provide this critical information.
Primary Objective: To investigate the bioequivalence of oral single whole tablet and crushed tablet of Genvoya in healthy volunteers, by characterizing the serum Area Under the Curve 0 to infinity (AUC0-∞) and Cmax of EVG, COBI, FTC, and TAF in plasma, after single doses of whole tablet and crushed tablet of this fixed dose antiretroviral combination in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female research participants, ≥18 years of age.
- •Negative HIV-1/2 Ag/Ab serology documented within 30 days prior to study entry.
- •Negative Hepatitis B surface antigen within 30 days prior to study entry.
- •Ability and willingness of subject to provide a signed informed consent and comply with study requirements.
- •Negative qualitative urine pregnancy test.
- •All subjects must not participate purposely in a conception process (e.g., active attempt to impregnate, sperm donation, or in vitro fertilization). If participating in sexual activity that could lead to pregnancy subjects must take every precaution to avoid risk of pregnancy by using a reliable contraception for the duration of the study therapy (e.g., condoms, hormonal, barrier).
- •Laboratory values and physical examination as judged by the principal investigator to be safe to participate including normal renal function.
- •Good peripheral venous access for proposed pharmacokinetic sampling.
- •Willingness and ability to take oral medications.
排除标准
- •History of chronic or acute medical conditions that in the opinion of the investigator would jeopardize safety of subjects participating in this study.
- •Known or suspected hypersensitivity to the components of Genvoya.
- •Use of prescription or over-the-counter medications, including agents containing polyvalent cations (e.g., Mg, Al, Fe, or Ca), or any other drugs that in the opinion of the investigator could interfere with the pharmacokinetics of any of the ARV components of Genvoya within 2 weeks prior to either study dose.
- •Pregnant or breast feeding.
- •Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- •Hospitalization or therapy for serious illness within 30 days prior to study entry as judged by the investigator.
- •Participation in any investigational drug study within 30 days prior to study entry that in the opinion of the investigator would preclude study participation.
- •Taking any medication listed in the package insert that is contraindicated with Genvoya.
研究组 & 干预措施
Genvoya Crushed Dose
Single observed oral dose of Genvoya crushed tablet
干预措施: Genvoya Crushed Dose (Drug)
Genvoya Oral dose
Single observed oral dose of Genvoya whole tablet
干预措施: Genvoya Oral dose (Drug)
结局指标
主要结局
AUC0-∞ for FTC
时间窗: 72 hours
AUC 0 to Infinity for Emtricitabine (ng\*h/mL)
AUC0-∞ for Tenofovir (TFV)
时间窗: 72 hours
AUC 0 to Infinity for TFV (ng\*h/mL)
Area Under the Curve From 0 to Infinity (AUC0-∞) for EVG
时间窗: 72 hours
AUC 0 to Infinity for Elvitegravir (ng\*h/mL)
AUC0-∞ for COBI
时间窗: 72 hours
AUC 0 to Infinity for Cobicistat (ng\*h/mL)
次要结局
- FTC Half-life(72 hours)
- COBI Half-life(72 hours)
- TFV Half-life(72 hours)
- EVG Cmax(72 Hr)
- FTC Cmax(72 hr)
- EVG Half-life(72 hours)
- TFV Cmax(72 hr)