A Phase I, Randomized, Cross-over, Single-Center, Single Dose Fasted Study of EG-101 IV Injection (EG-ZNMP-01) in Healthy Volunteers to Serve as a Safety Lead-In for Dosing in Pregnant Women With Severe Pre-eclampsia
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 24
- 主要终点
- Tmax
研究概览
简要总结
Preeclampsia is one of the leading causes of maternal and fetal death. It is a syndrome of pregnant women and is usually characterized by new onset of hypertension and proteinuria after 20 weeks of gestation. This disease is a multisystem disorder affects most maternal organs, predominantly the vascular, renal, hepatic, cerebral and coagulation systems. While hypertension is almost always a symptom of this disease, preeclampsia is not the same as essential hypertension.
This is a single-center, randomized, open-label, 4 period, 3-way crossover, single dose fasted study to evaluate the safety, tolerability and pharmacokinetics of four ascending doses of the EG-101 IV injection in healthy volunteers.
Twenty-four subjects in total, with eight subjects randomly assigned to one of three different sequences for variation of doses under fasted conditions. Dosing duration is approximately 4 weeks and followed by the follow-up for each subject.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy adult female volunteers, 18 to 55 years of age, inclusive, at first Check-In Visit
- •Body mass index (BMI) ≥18.5 to ≤32 kg/m2 at Screening (calculated as a function of measured height and weight according to the formula, BMI = kg / m2 where m2 is height in meters squared.)
- •All female subjects must be nonpregnant, nonlactating and either postmenopausal, surgically sterile, or using contraceptive regimens more than 3 months. All females must have a negative serum pregnancy test at Screening and Check-in Visit. Effective methods of contraception include a dual method of contraception: condom with spermicide in conjunction with use of an intrauterine device (IUD), condom with spermicide in conjunction with use of a diaphragm, condom with birth control patch or vaginal ring, or condom with oral, injectable, or implanted contraceptive. Surgical sterility is documented through documented: hysterectomy, partial hysterectomy, bilateral oophorectomy, or bilateral tubal ligation at least 6 months prior to Screening. Postmenopausal sterility is documented by absence of menses for at least 12 months prior to Screening plus serum FSH ≥40 mIU/mL and estradiol <30 pg/mL at screening
- •Male subjects, are not enrolled into this study
- •Medically healthy on the basis of medical history, and physical examination (including but not limited to an evaluation of the cardiovascular, gastrointestinal, respiratory, and central nervous systems), as determined by the Investigator at Screening and each Check-In Visit
排除标准
- •Females who are pregnant, lactating, or likely to become pregnant during the study
- •History and/or recent evidence within 6 months prior to Screening of alcohol or drug/substance abuse disorder
- •Subjects with a history of hypersensitivity to Zanamivir or any component of study medication
- •History of clinically significant allergies including drug allergies or allergic bronchial asthma or related bronchospastic conditions
- •Subjects who have history of unexplained syncope or fainting or a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia or dehydration
研究组 & 干预措施
Group 1: treatment sequences ABC+D
Period 1
Drug: EG-101 100 mg IVPB once (Level A)
Period 2
Drug: EG-101 400 mg IVPB once (Level B)
Period 3
Drug: EG-101 600 mg IVPB once (Level C)
Period 4
Drug: EG-101 600 mg IVPB twice, 8 hours apart (Level D)
干预措施: EG-101 (Drug)
Group 2: treatment sequence: BCA+D
Period 1
Drug: EG-101 400 mg IVPB once (Level B)
Period 2
Drug: EG-101 600 mg IVPB once (Level C)
Period 3
Drug: EG-101 100 mg IVPB once (Level A)
Period 4
Drug: EG-101 600 mg IVPB twice, 8 hours apart (Level D)
干预措施: EG-101 (Drug)
Group 3: treatment sequence: CAB+D
Period 1
Drug: EG-101 600 mg IVPB once (Level C)
Period 2
Drug: EG-101 100 mg IVPB once (Level A)
Period 3
Drug: EG-101 400 mg IVPB once (Level B)
Period 4
Drug: EG-101 600 mg IVPB twice, 8 hours apart (Level D)
干预措施: EG-101 (Drug)
结局指标
主要结局
Tmax
时间窗: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose
Time to Maximum Concentration
Cmax
时间窗: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose
Maximum Plasma Concentration
AUC
时间窗: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose
Area Under the Plasma Concentration-time Curve
CL/F
时间窗: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose
Apparent Plasma Clearance
Vd/F
时间窗: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose
Apparent Volume of Distribution
t½
时间窗: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose
Terminal Elimination Half-life
Ae
时间窗: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose
Cumulative Amount Excreted Unchanged in Urine
次要结局
- Incidence of reported adverse events(From baseline through to post study Follow-up (up to 5 weeks))
- Blood pressure(From screening throughout the study duration to post study Follow-up (up to 5 weeks))
- Respiratory rate(From screening throughout the study duration to post study Follow-up (up to 5 weeks))
- Pulse rate(From screening throughout the study duration to post study Follow-up (up to 5 weeks))
- Body temperature(From screening throughout the study duration to post study Follow-up (up to 5 weeks))
- 12-lead electrocardiograms (ECG)(At the screening day, Day 1 pre-dose and 6 hours post-dose)
- Prothrombin time (PT)(On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks))
- White Blood Cell count(On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks))
- Albumin(On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks))
- Protein(On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks))