NCT02914353

Study to Evaluate Safety, PK and PD of Single and Multiple Ascending Doses of EP-7041 in Healthy Subjects

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate The Safety Tolerability, Pharmacokinetics, and Pharmacodynamcs of Single and Multiple Ascending Doses of EP-7041 in Hea;Thy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: eXIthera Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

This First-In-Human study will evaluate the safety and tolerability, pharmacokinetic profile, and pharmacodynamic effects of EP-7041, a novel Factor XIa inhibitor, following IV administration of single ascending doses in healthy normal volunteers, and following continuous IV infusions of multiple ascending doses in healthy normal volunteers.

Detailed description

This will be a single-center, Phase 1a/1b, placebo-controlled, randomized, double-blind, integrated sequential ascending dose / multiple ascending dose study. The study will be divided into two parts: the single ascending dose evaluation in healthy normal volunteers will constitute Part A and the multiple ascending doses evaluation in healthy normal volunteers will constitute Part B. The two study parts will be performed sequentially with partial overlapping. Part A will include up to 6 cohorts (1 cohort per dose level; 4 planned cohorts and 2 optional adaptive cohorts). Each cohort will include 8 subjects - 6 on active drug and 2 on placebo - resulting in a maximum number of 48 subjects in the study - 32 planned and 16 optional. Subjects in each cohort will receive a single IV slow bolus (50 mL over 5 minutes) administration of study medication or placebo. The dose of EP-7041 will be sequentially escalated cohort by cohort in Part A . A staggered dosing schedule will be used for each cohort of Part A: 2 sentinel subjects (1 active and 1 placebo) will be dosed first and the remaining 6 subjects will be dosed the next day (5 active and 1 placebo). Part B will include up to 4 cohorts (1 cohort per dose level; 3 planned cohorts and 1 optional adaptive cohort). As in Part A, each cohort of Part B will include 6 subjects on active drug and 2 on placebo, for a total of 8 subjects per cohort. Part B will therefore involve, at maximum, 32 subjects, with 24 planned subjects an 8 optional subjects. Subjects in each cohort of Part B will receive a total of 5 sequential 24-hour IV infusions of EP-7041 or matching placebo. Evaluation of safety and tolerability to EP-7041 will include adverse events (i.e., seriousness, severity, relationship to EP-7041), vital signs, ECG, clinical laboratory parameters, physical examination, local response to each injection, and body weight. Pharmacokinetic analyses will be performed with measurements of EP-7041 plasma concentrations, following single and multiple IV doses. Pharmacodynamic effects of EP-7041 will be evaluated through the measurement of aPTT and PT in all subjects at multiple times throughout the course of both studies.

Conditions

• Arthroplasty, Replacement, Knee

Interventions

Type	Name	Description
DRUG	EP=7041	Factor X!a Inhibitor
DRUG	Placebo	Normal Saline

Timeline

• Start date: 2016-07-01
• Primary completion: 2017-05-01
• Completion: 2017-05-01
• First posted: 2016-09-26
• Last updated: 2017-05-31

Locations

1 site across 1 country: Australia