Pharmacokinetic Study to Evaluate Safety and Tolerability of EG-101 in Healthy Female Volunteers as a Safety Lead-In for Dosing in Pregnant Women With Severe Pre-eclampsia

Official title

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

Overview

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.

Interventions

• Drug EG-101
  EG-ZNMP-01 IV injection 10 mg/mL, 20 mL vial

Primary outcome measures

• Tmax [Time frame: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose]
• Cmax [Time frame: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose]
• AUC [Time frame: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose]
• CL/F [Time frame: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose]
• Vd/F [Time frame: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose]
• t½ [Time frame: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose]
• Ae [Time frame: Day 1 pre-dose and at multiple timepoints (up to 32 hours) post-dose]

Secondary outcome measures (10)

• Incidence of reported adverse events [Time frame: From baseline through to post study Follow-up (up to 5 weeks)]
• Blood pressure [Time frame: From screening throughout the study duration to post study Follow-up (up to 5 weeks)]
• Respiratory rate [Time frame: From screening throughout the study duration to post study Follow-up (up to 5 weeks)]
• Pulse rate [Time frame: From screening throughout the study duration to post study Follow-up (up to 5 weeks)]
• Body temperature [Time frame: From screening throughout the study duration to post study Follow-up (up to 5 weeks)]
• 12-lead electrocardiograms (ECG) [Time frame: At the screening day, Day 1 pre-dose and 6 hours post-dose]
• Prothrombin time (PT) [Time frame: On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks)]
• White Blood Cell count [Time frame: On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks)]
• Albumin [Time frame: On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks)]
• Protein [Time frame: On screening day, check-in day (D-1), and during post study Follow-up (up to 5 weeks)]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07327255 · EG-101-1.1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗