A Phase I, Open-label, Fixed Sequence, Two-period, Crossover, Drug-drug Interaction Study to Investigate the Interaction Potential of Itraconazole on the Pharmacokinetics of Ganaplacide and Lumefantrine Combination in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Apparent volume of distribution during terminal elimination phase following extravascular administration (Vz/F) for Ganaplacide and Lumefantrine
研究概览
简要总结
The study will assess the effect of multiple doses of itraconazole, a strong CYP3A4/5 inhibitor, on the PK of ganaplacide and lumefantrine in healthy participants. This study will provide data that is relevant for advice regarding possible concomitant medications that are inhibitors of CYP3A4/5 in future clinical studies with ganaplacide and lumefantrine and for potential future labeling considerations
详细描述
This is an open-label, fixed sequence, 2-period, crossover, drug-drug interaction (DDI) study, to evaluate the effect of multiple doses of itraconazole on the single dose PK of ganaplacide and lumefantrine in healthy participants.
The study will consist of a screening period of up to 28 days, 2 Baseline evaluations (on Day -1 of each treatment period), and 2 treatment periods which are separated by a washout period. Participants who meet the eligibility criteria at Screening will be admitted to the study site for First Baseline evaluations on Day -1 of Period 1. Baseline safety assessments will be performed prior to first dosing of study treatment in each period.
Participants enrolled will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1. In Period 2, participants will receive itraconazole once daily (q.d.) on Days 1 to 18 and a single dose of ganaplacide and lumefantrine combination on Day 5, approximately 2 hours after the itraconazole dose. There will be 336 hours of sequential blood sampling for PK assessment starting after ganaplacide and lumefantrine dosing in each treatment period. Between the 2 treatment periods, there will be an additional washout period of at least 14 days, beginning from the last PK sample collection in Period 1 and continuing until the first dose of study treatment in Period 2.
Each dose of ganaplacide and lumefantrine combination will be administered after at least 10 hours of overnight fasting and will be followed by at least 4 hours of fasting post dose. In Period 2, itraconazole will be administered after at least 10 hours of overnight fasting and followed by at least 1 hour of fasting post dose (except on Day 5 when ganaplacide and lumefantrine will be administered approximately 2 hours after itraconazole dosing and participants will continue fasting for at least 4 hours post ganaplacide and lumefantrine dosing).
Safety assessments (including physical examinations, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations [hematology, chemistry, coagulation, and urinalysis], and adverse event [AE] and serious adverse event [SAE] monitoring) will be performed during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 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
- •Signed informed consent must be obtained prior to participation in the study.
- •Healthy male and non-childbearing potential female participants 18 to 55 years of age inclusive, at Screening.
- •In good health as determined by medical history, physical examination, vital signs, ECG, and clinical laboratory tests at Screening.
- •Must weigh at least 50 kg with a body mass index (BMI) within the range of 18 to 29.9 kg/m2 inclusive, at Screening.
排除标准
- •Use of other investigational drugs within 5 half-lives or 30 days prior to first dosing of study treatment, whichever is longer.
- •Known family history or known presence of long QT syndrome.
- •Known history or current clinically significant arrhythmias.
- •History or presence of malignancy of any organ system (other than treated localized basal cell or squamous cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within 5 years of Screening, regardless of whether there is evidence of local recurrence or metastases.
- •History or presence of duodenal ulcer, ulcerative colitis, or Crohn's disease.
- •Presence of active or uncontrolled thyroid disease.
- •Has had cholecystectomy (gallbladder removed).
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Group 1
Each participant will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1. In Period 2, participants will receive itraconazole q.d. on Days 1 to 18 and a single dose of ganaplacide and lumefantrine combination on Day 5, approximately 2 hours after the itraconazole dose
干预措施: Ganaplacide (Drug)
Group 1
Each participant will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1. In Period 2, participants will receive itraconazole q.d. on Days 1 to 18 and a single dose of ganaplacide and lumefantrine combination on Day 5, approximately 2 hours after the itraconazole dose
干预措施: Lumefantrine (Combination Product)
Group 1
Each participant will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1. In Period 2, participants will receive itraconazole q.d. on Days 1 to 18 and a single dose of ganaplacide and lumefantrine combination on Day 5, approximately 2 hours after the itraconazole dose
干预措施: Itraconazole (Drug)
结局指标
主要结局
Apparent volume of distribution during terminal elimination phase following extravascular administration (Vz/F) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz/F will be listed and summarized using descriptive statistics.
Observed maximum plasma concentration (Cmax) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.
Area under the concentration-time curve from time zero (pre-dose) to the 24-hour time point (AUC^0-24) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC\^0-24 will be listed and summarized using descriptive statistics.
Terminal elimination half-life (T^1/2) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. T\^1/2 will be listed and summarized using descriptive statistics.
Time of maximum observed drug concentration occurrence (Tmax) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Apparent total body clearance of drug from plasma following extravascular administration (CL/F) for Ganaplacide and Lumefantrine
时间窗: 0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose)
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL/F will be listed and summarized using descriptive statistics.
次要结局
- Terminal elimination half-life (T^1/2) for Ganaplacide metabolites (RHF218 and GOU089)(0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose))
- Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) for Ganaplacide metabolites (RHF218 and GOU089)(0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose))
- Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) for Ganaplacide metabolites (RHF218 and GOU089)(0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose))
- Observed maximum plasma concentration (Cmax) for Ganaplacide metabolites (RHF218 and GOU089)(0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose))
- Time of maximum observed drug concentration occurrence (Tmax) for Ganaplacide metabolites (RHF218 and GOU089)(0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose))
- Metabolite to Parent Ratio (MR) for Ganaplacide metabolites (RHF218 and GOU089)(0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose))
- Area under the concentration-time curve from time zero (pre-dose) to the 24-hour time point (AUC0-24) for Ganaplacide metabolites (RHF218 and GOU089)(0 (pre-dose), 0.5, 1, 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours (post dose))