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

NCT02914353 | Completed Phase 1

• 1 other identifier: EXI-111
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Arthroplasty, Replacement, Knee

Keywords

Factor X!a; anticoagulant; thromboembolism; venous thromboembolism; embolism and thrombosis; enzyme inhibitors; hematologic agent

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 following a single IV bolus of EP-7041

  Assessment of safety and tolerability to EP-7041, administered as a single IV bolus, will be based on adverse events. Each AE will be graded with respect to its relationship to treatment using five categories: not related, unlikely, possible, probable, and highly probable. Each AE will also be graded on a three-point severity scale: mild, moderate, and severe. Adverse events will be coded by body system and preferred term using the MedDRA (Medical Dictionary for Regulatory Activities) dictionary. Assessments as to the effect of EP-7041 on vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight will also be made. The number and percentage of subjects experiencing adverse events will be tabulated for each treatment group by body system and preferred term. The number and percentage of subjects experiencing AEs will also be tabulated by relationship to drug treatment and by severity. If an AE is

  Adverse events will be collected and documented during the course of the study. For a period of 30 days following the last study drug administration, adverse events will also be documented if reported.

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 following a continuous IV infusion of EP-7041 administered over 5 days

  Assessment of safety and tolerability to EP-7041, administered as a continuous IV infusion over 5 days, will be based on adverse events. Each AE will be graded with respect to its relationship to treatment using five categories: not related, unlikely, possible, probable, and highly probable. Each AE will also be graded on a 3-point severity scale: mild, moderate, and severe. Adverse events will be coded by body system and preferred term using the Medical Dictionary for Regulatory Activities dictionary. Assessments as to the effect of EP-7041 on vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight will also be made. The number and percentage of subjects experiencing adverse events will be tabulated for each treatment group by body system and preferred term. The number and percentage of subjects experiencing AEs will also be tabulated by relationship to drug treatment and by severity.

  Adverse events will be collected and documented during the course of the study. For a period of 30 days following the last study drug administration, adverse events will also be documented if reported.

Secondary Outcomes (17)

• Measurement of Maximum Plasma Concentration Achieved Following a Single IV Bolus of EP-7041

  24 hours

• Measurement of Time of Maximum Plasma Concentration Following a Single IV Bolus of EP-7041

  24 hours

• Measurement of Plasma Half-Life Following a Single IV Bolus of EP-7041

  24 hours

• Measurement of ClearanceFollowing a Single IV Bolus of EP-7041

  24 hours

• Measurement of the Area Under the Plasma Concentration versus Time Curve Following a Single IV Bolus of EP-7041

  24 hours

Study Arms (2)

Experimental - EP-7041

EXPERIMENTAL

Single Ascending Dose: Single IV dose for each cohort; dose range 0.01 mg/kg to 1.0 mg/kg Multiple Ascending Dose: 0.01 mg/kg/h - 5 x 24 h continuous infusion up to 0.6 mg/kg/h - 5 x 24 h continuous infusion

Drug: EP=7041

Placebo - Sterile Saline

PLACEBO COMPARATOR

Single Ascending Dose: Single IV dose for each cohort; Multiple Ascending Dose: 5 x 24 h continuous infusion for each cohort

Drug: Placebo

Interventions

EP=7041 DRUG

Factor X!a Inhibitor

Experimental - EP-7041

Placebo DRUG

Normal Saline

Placebo - Sterile Saline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female, non-smoker (no use of tobacco products within 3 months prior to screening), ≥18 and ≤60 years of age, with Body Mass Index (BMI) \> 18.5 and \< 32.0 kg/m2 and a weight of at least 60 kg but not greater than 100 kg.
• Healthy as defined by:
• No history of abnormal bleeding episodes, e.g. nosebleeds, or abnormally heavy periods, or extensive bleeding after injury, surgery or dental work.
• A normal short physical examination and normal vital signs (heart rate (HR), blood pressure (BP) and tympanic body temperature).
• Normal laboratory tests (hematology, biochemistry, urinalysis, coagulation tests (aPTT and PT).
• the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
• the absence of clinically significant history of neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.

You may not qualify if:

• Use of any drugs known to induce or inhibit hepatic drug metabolism within 30 days prior to drug administration.
• Positive pregnancy test at screening or check-in (Day -1).
• Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood pressure lower than 90 or over 160 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less than 40 or over 100 bpm) at screening or check-in (Day -1).
• Participation in a clinical trial involving the administration of an investigational or marketed drug within 30 days (90 days for biologics), or five (5) half-lives, whichever is longer, prior to the first dosing or concomitant participation in an investigational study involving no drug administration.
• Hemoglobin or hematocrit clinically significantly less than lower limits of normal at screening.

Sponsors & Collaborators

• eXIthera Pharmaceuticals: lead
• IDT CMAX Clinical Trials: collaborator
• Syneos Health: collaborator
• CPR Pharma Services Pty Ltd, Australia: collaborator

Study Sites (1)

IDT CMAX

Adelaide, South Australia, Australia

Location

MeSH Terms

Conditions

Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Sepehr Shakib, MD

  IDT CMAX

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2016
• First Posted: September 26, 2016
• Study Start: July 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: May 31, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)