Study to Evaluate Safety, PK and PD of Single and Multiple Ascending Doses of EP-7041 in Healthy Subjects
Condition: Arthroplasty, Replacement, Knee
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): EP=7041; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Factor X!a Inhibitor; Normal Saline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Factor X!a; anticoagulant; thromboembolism; venous thromboembolism; embolism and thrombosis; enzyme inhibitors; hematologic agent