Study to Assess the Pharmacokinetic Drug - Drug Interactions Between Atazanavir Plus Ritonavir Coadministered With Voriconazole in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 185
- 试验地点
- 2
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in Participants Who Are Extensive Metabolizers (EM)
研究概览
简要总结
This study assesses the effects of voriconazole, 200 mg, administered twice daily (BID), on the steady-state pharmacokinetics of atazanavir administered as atazanavir/ritonavir, 300/100 mg once daily (QD), in healthy participants with functional CYP2C19 alleles. The study also reviews the effects of atazanavir/ritonavir, 300/100 mg QD, on the pharmacokinetics of voriconazole, 200 mg, BID in healthy participants with functional CYP2C19 alleles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants as determined by no clinically significant deviation from normal
- •Body Mass Index (BMI) of 18 to 32 kg/m^2, inclusive. BMI=weight(kg)/height (m)^2
- •Women who are not of childbearing potential (WOCBP)(ie, who are postmenopausal or surgically sterile) and men, ages 18 to 45 years, inclusive
排除标准
- •Sexually active fertile men not using effective birth control if their partners are WOCBP
- •Proven or suspected acute hepatitis (within 12 months prior to the 1st dose)
- •Any significant acute or chronic medical illness
- •Any gastrointestinal surgery that could impact on the absorption of study drug
- •Smoking more than 5 cigarettes per day
- •History of any hemolytic disorders (including drug-induced hemolysis)
- •History of acute or chronic pancreatitis
- •History of hypochlorhydria or achlorhydria
- •Men and women weighing <40 kg
- •Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or HIV-2 antibody
- •Patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
研究组 & 干预措施
Voriconazole, 200 mg BID (EM)
干预措施: Voriconazole (Drug)
Atazanavir/Ritonavir, 300/100 QD (EM & PM)
干预措施: Atazanavir (Drug)
Atazanavir/Ritonavir, 300/100 QD (EM & PM)
干预措施: Ritonavir (Drug)
Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM)
干预措施: Voriconazole (Drug)
Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM)
干预措施: Atazanavir (Drug)
Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM)
干预措施: Ritonavir (Drug)
Voriconazole, 50 mg BID (PM)
干预措施: Voriconazole (Drug)
Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM)
干预措施: Voriconazole (Drug)
Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM)
干预措施: Atazanavir (Drug)
Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM)
干预措施: Ritonavir (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in Participants Who Are Extensive Metabolizers (EM)
时间窗: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle
EM participants are those with functional CYP2C19 alleles.
Time to Maximum Concentration (Tmax) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants
时间窗: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle
EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
Area Under the Plasma Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] of Atazanavir Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants
时间窗: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle
EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
Tmax of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants
时间窗: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle
Tmax=time to maximum concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
Cmax and Cmin of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants
时间窗: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle
Cmax=maximum observed plasma concentration; Cmin=minimum observed plasma concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
AUC(TAU)of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants
时间窗: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle
AUC(TAU)=area under the plasma concentration-time curve in 1 dosing interval; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.
次要结局
- Cmax and Cmin of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants(Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle)
- Tmax of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants(Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle)
- AUC(TAU) of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants(Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle)
- Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Any AE(Days 1 to 31 (discharge), continuously)
- Number of Participants With Marked Abnormalities in Serum Chemistry Test Results(Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge))
- Number of Participants With Marked Abnormalities in Hematology Laboratory Test and Urinalysis Results(Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge))
- Number of Participants With Investigator-identified Abnormalities in Electrocardiogram Results Not Present Prior to Administration of Study Drug and Considered Not Relevant and Not AEs by Investigator(Within 21 days of Day 1 and on Days -1, 21, and 31 (at discharge))
- Number of Participants With Abnormalities in Vital Signs(Within 21 days of Day 1 and on Days -1, 1, 3, 11, 21, and 31 (at discharge))