A Phase 1, Randomized, Open-Label Study to Evaluate the Effect of Vapendavir (BTA798) on the Pharmacokinetics of Orally Administered Midazolam, a CYP3A4 Substrate, in Healthy Male and Female Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- The Effect of Vapendavir on the PK Profile of Midazolam
研究概览
简要总结
The primary aim of this Phase 1 study is to evaluate the effect of vapendavir daily doses of 528 mg daily (QD) and 264 mg twice daily (BID) on the pharmacokinetic (PK) profile of midazolam, a cytochrome (CYP) 3A4 substrate. Additionally, the effect of midazolam on the PK profile of vapendavir, a PK profile comparison of vapendavir in males and females, as well as the safety of vapendavir will also be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Must be male or female between 18 and 55 years of age (inclusive) with BMI between 18 and 30 kg/m2 (inclusive), and weight ≥50 kg at the time of screening;
- •Capable of giving written informed consent;
- •Subject is able to understand and comply with the protocol requirements, instructions and restrictions;
- •Healthy on the basis of physical examination, medical history, medication usage, vital signs (VS), electrocardiograms (ECGs), and clinical laboratory tests;
- •Female subjects who are not post-menopausal for at least 2 years or surgically sterile with complete hysterectomy or bilateral oophorectomy and male subjects who are not surgically sterile via vasectomy, must agree to use a double barrier method of birth control, such as a condom plus spermicidal agent (foam/gel/film/cream/suppository); and
- •Female subjects must not be breastfeeding or pregnant.
排除标准
- •Positive results for Hepatitis B, Hepatitis C, or HIV;
- •Frequent use (defined as > 5 times/day) of tobacco products, including cigarettes, cigars, chewing tobacco;
- •A medical history of significant hematological, gastrointestinal, respiratory, renal, hepatic, cerebrovascular, immunologic, psychiatric or cardiovascular disease or event;
- •Current or recent respiratory infection (defined as within 14 days of first study visit participation)
- •Presence or history of significant allergy;
- •Clinically significant abnormalities noted on ECG;
- •Screening vital signs representing sustained elevated systolic blood pressure <90 mmHg or >140 mmHg, and/or diastolic blood pressure <55 mmHg or >90 mmHg.
- •Presence of significant gastrointestinal abnormalities such as diarrhea or constipation;
- •Safety laboratory abnormalities noted at screening which are clinically significant
- •Current or defined history of abuse of alcohol or illicit drugs;
- •A positive pregnancy test at screening;
- •Poor vein access or fear of venipuncture or sight of blood; and
- •Regular consumption of alcohol defined as either > 2 units (glass or shot) of alcoholic beverages per day or > 14 units per week.
研究组 & 干预措施
Vapendavir 528 mg QD
Twelve subjects (6 male and 6 female) will receive 528 mg vapendavir (achieved with four 132 mg vapendavir capsules) QD in the morning for seven days
干预措施: Midazolam 5mg Syrup (Drug)
Vapendavir 528 mg QD
Twelve subjects (6 male and 6 female) will receive 528 mg vapendavir (achieved with four 132 mg vapendavir capsules) QD in the morning for seven days
干预措施: Vapendavir 528 mg QD (Drug)
Vapendavir 264 mg BID
Twelve subjects (6 male and 6 female) will receive 264 mg vapendavir (achieved with two 132 mg vapendavir capsules) BID daily as divided dose given in the morning and evening 12 hours apart for seven days.
干预措施: Midazolam 5mg Syrup (Drug)
Vapendavir 264 mg BID
Twelve subjects (6 male and 6 female) will receive 264 mg vapendavir (achieved with two 132 mg vapendavir capsules) BID daily as divided dose given in the morning and evening 12 hours apart for seven days.
干预措施: Vapendavir 264 mg BID (Drug)
结局指标
主要结局
The Effect of Vapendavir on the PK Profile of Midazolam
时间窗: End of Study (up to 46 weeks in duration)
To evaluate the effect of vapendavir daily dose of 528 mg QD on the PK profile of midazolam, a CYP3A4 substrate. The primary outcome will be evaluated through a series of analyses of PK parameters including: * for midazolam including maximum observed plasma concentration (Cmax) * time at which Cmax was observed (Tmax) * plasma concentration at the end of the dosing interval (Ctau) * area under the plasma concentration-time curve from time 0 to the last measurable plasma concentration (AUC0-last) * area under the plasma concentration-time curve from time 0 to the end of the dosing interval (AUC0-tau) * area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) * elimination half-life (t1/2) * apparent oral clearance (CL/F) * apparent oral volume of distribution (Vz/F).
次要结局
- Assess the Safety of Vapendavir(End of Study (up to 46 weeks in duration)
- Assess Whether PK Profile of Vapendavir is Affected by Presence of Midazolam(End of Study (up to 46 weeks in duration))