A Phase 1 Pharmacokinetic Drug-Drug Interaction Study of Benznidazole and E1224 in Healthy Male Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Maximum serum concentration (Cmax) of Benznidazole
研究概览
简要总结
The purpose of this study is to determine whether benznidazole and E1224 should be administered concomitantly in patients with Chagas Disease as not enough data are available. This study aims to assess cross interactions of these two compounds.
详细描述
Benznidazole and E1224 are intended to be administered concomitantly in patients with Chagas disease. Thus, an in vivo interaction study in healthy volunteers may be justified as the two drugs are intended to be administered concomitantly in patients and no in vivo nor in vitro data are available.
In addition both interactions (potential for benznidazole to interact on the pharmacokinetic (PK) of E1224 and potential for E1224 on the PK of benznidazole should be studied.
Benznidazole t1/2 is quite short (12 h) whereas E1224 t1/2 is very long (more than 200 h). Therefore it was chosen to study the interaction of E1224 at steady-state while interaction of benznidazole after single dose appears more appropriate instead of a classical randomized cross-over design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male healthy volunteers 18 to 45 years of age;
- •Light smokers (less than 5 cigarettes per day) or subjects who are non-smokers;
- •Male subjects with a body weight of at least 50 kg and a body mass index (BMI) calculated as weight in kg/height (in m2) from 18 to 28 kg/m2 at screening;
- •Able to communicate well with the Investigator and research staff and to comply with the requirements of the entire study;
- •Provision of written informed consent to participate as shown by a signature on the volunteer consent form;
排除标准
- •Who on direct questioning and physical examination have evidence of any clinically significant acute or chronic disease, including known or suspected HIV, hepatites B virus (HBV) or hepatites C virus (HCV) infection;
- •Who has positive diagnosis of T. cruzi infection indicated by Conventional serology;
- •With any clinically significant abnormality following review of pre-study laboratory tests, vital signs, full physical examination and 12-lead ECG;
- •Who forfeit their freedom by administrative or legal award or who were under guardianship;
- •Unwilling to give their informed consent;
- •Who have a positive laboratory test for Hepatitis B surface antigen (HbsAg), or anti-HIV 1/2 or anti- HCV antibodies;
- •Who have a history of allergy (serious or not), allergic skin rash, asthma, intolerance, sensitivity or photosensitivity to any drug;
- •Who are known or suspected alcohol or drug abusers (more than 14 units of alcohol per week, one unit = 8 g or about 10 mL of pure alcohol);
研究组 & 干预措施
Benznidazole and E1224
Benznidazole and E1224
干预措施: Benznidazole (Drug)
Benznidazole and E1224
Benznidazole and E1224
干预措施: E1224 (Drug)
结局指标
主要结局
Maximum serum concentration (Cmax) of Benznidazole
时间窗: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Time of occurrence of maximum plasma concentration (tmax) of Benznidazole
时间窗: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Area under the serum concentration versus time curve from time zero to the time (t) corresponding to the last quantifiable concentration (AUC 0-t) of Benznidazole
时间窗: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase (AUC 0-∞) of Benznidazole
时间窗: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Maximum serum concentration (Cmax) of Ravuconazole.
时间窗: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Time of occurrence of maximum plasma concentration (tmax) of Ravuconazole.
时间窗: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
Terminal half-life (t1/2) of Benznidazole
时间窗: Day 1 and day 9
BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
The area under the blood drug concentration vs. time curve from time zero (pre-dose) to 24 h post-dose (AUC 0-24)
时间窗: Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose)
PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly.
次要结局
- Incidence of Adverse Events (AEs)(Through study completion, i.e up to 22 days.)
- Clinically significant alterations in pulse rate(Through study completion, i.e up to 22 days.)
- Clinically significant alterations in blood pressure(Through study completion, i.e up to 22 days.)
- Clinically significant alterations in 12-lead ECG(Through study completion, i.e up to 22 days.)
- Clinically significant Haematology abnormalities (hemoglobin, RBC, hematocrit, MCV, MCH, MCHC, WBC, including differential, platelet counts)(Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose)
- Clinically significant Biochemistry abnormalities (albumin (ALB), ALP, ALT, AST, gamma-glutamyl transferase (GGT), chlorides (Cl-), creatinine, glucose (GLU), potassium (K+), sodium (Na+), total bilirubin (TBIL), total proteins (TP), Urea.(Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose)
- Clinically significant Urinalysis abnormalities (leukocytes, pH, proteins, urobilinogen, blood, nitrites, glucose, ketone bodies, bilirubin).(Screening and day 22)