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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02914353




Registration number
NCT02914353
Ethics application status
Date submitted
19/09/2016
Date registered
26/09/2016
Date last updated
31/05/2017

Titles & IDs
Public title
Study to Evaluate Safety, PK and PD of Single and Multiple Ascending Doses of EP-7041 in Healthy Subjects
Scientific title
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
Secondary ID [1] 0 0
EXI-111
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthroplasty, Replacement, Knee 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EP=7041
Treatment: Drugs - Placebo

Experimental: Experimental - EP-7041 - 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

Placebo Comparator: Placebo - Sterile Saline - Single Ascending Dose: Single IV dose for each cohort;
Multiple Ascending Dose: 5 x 24 h continuous infusion for each cohort


Treatment: Drugs: EP=7041
Factor X!a Inhibitor

Treatment: Drugs: Placebo
Normal Saline

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
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.
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
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 outcome [1] 0 0
Measurement of Maximum Plasma Concentration Achieved Following a Single IV Bolus of EP-7041 - Maximum Plasma Concentration (Cmax)
Timepoint [1] 0 0
24 hours
Secondary outcome [2] 0 0
Measurement of Time of Maximum Plasma Concentration Following a Single IV Bolus of EP-7041 - Time of Maximum Plasma Concentration (Tmax)
Timepoint [2] 0 0
24 hours
Secondary outcome [3] 0 0
Measurement of Plasma Half-Life Following a Single IV Bolus of EP-7041 - Plasma Half-Life (T½)
Timepoint [3] 0 0
24 hours
Secondary outcome [4] 0 0
Measurement of ClearanceFollowing a Single IV Bolus of EP-7041 - Clearance (CL)
Timepoint [4] 0 0
24 hours
Secondary outcome [5] 0 0
Measurement of the Area Under the Plasma Concentration versus Time Curve Following a Single IV Bolus of EP-7041 - Area Under the Curve (AUC)
Timepoint [5] 0 0
24 hours
Secondary outcome [6] 0 0
Measurement of the Elimination Rate Constant Following a Single IV Bolus of EP-7041 - Elimination Rate Constant (Kel)
Timepoint [6] 0 0
24 hours
Secondary outcome [7] 0 0
Measurement of the Apparent Volume of Distribution Following a Single IV Bolus of EP-7041 - Apparent Volume of Distribution (Vd)
Timepoint [7] 0 0
24 hours
Secondary outcome [8] 0 0
Measurement of the Steady-State Concentration with a the Initiation of Continuous IV 5-day Infusion of EP-7041 - Concentration at Steady State (Css)
Timepoint [8] 0 0
6 days
Secondary outcome [9] 0 0
Measurement of the Time to Reach a Steady-State Concentration Following a the Initiation of Continuous IV 5-day Infusion of EP-7041 - Time to Reach Concentration at Steady State (Tss)
Timepoint [9] 0 0
6 days
Secondary outcome [10] 0 0
Measurement of the Clearance During the Course of a Continuous IV 5-day Infusion of EP-7041 - Clearance (CL)
Timepoint [10] 0 0
6 days
Secondary outcome [11] 0 0
Measurement of the Plasma Half-Life Following the Discontinuation of Continuous IV 5-day Infusion of EP-7041 - Plasma Half-Life (T½)
Timepoint [11] 0 0
6 day
Secondary outcome [12] 0 0
Measurement of Clotting Biomarker Activated Partial Thromboplastin Time Following a Single IV Bolus of EP-7041 - Activated Partial Thromboplastin Time (aPTT)
Timepoint [12] 0 0
1 day
Secondary outcome [13] 0 0
Measurement of Clotting Biomarker Activated Partial Thromboplastin Time During the Course of a Continuous IV 5-day Infusion of EP-7041 - Activated Partial Thromboplastin Time (aPTT)
Timepoint [13] 0 0
6 days
Secondary outcome [14] 0 0
Measurement of Clotting Biomarker Prothrombin Following a Single IV Bolus of EP-7041 - Prothrombin Time (PT)
Timepoint [14] 0 0
1 day
Secondary outcome [15] 0 0
Measurement of Clotting Biomarker Prothrombin During the Course of a Continuous IV 5-day Infusion of EP-7041 - Prothrombin Time (PT)
Timepoint [15] 0 0
6 day
Secondary outcome [16] 0 0
Measurement of Clotting Biomarker International Normalized Ratio Following a Single IV Bolus of EP-7041 - International Normalized Ratio (INR)
Timepoint [16] 0 0
1 day
Secondary outcome [17] 0 0
Measurement of Clotting Biomarker International Normalized Ratio During the Course of a Continuous IV 5-day Infusion of EP-7041 - International Normalized Ratio (INR)
Timepoint [17] 0 0
6 days

Eligibility
Key inclusion criteria
- 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:

1. No history of abnormal bleeding episodes, e.g. nosebleeds, or abnormally heavy
periods, or extensive bleeding after injury, surgery or dental work.

2. A normal short physical examination and normal vital signs (heart rate (HR),
blood pressure (BP) and tympanic body temperature).

3. Normal laboratory tests (hematology, biochemistry, urinalysis, coagulation tests
(aPTT and PT).

4. the absence of clinically significant illness and surgery within 4 weeks prior to
dosing.

5. the absence of clinically significant history of neurological, endocrinal,
cardiovascular, pulmonary, hematological, immunologic, psychiatric,
gastrointestinal, renal, hepatic, and metabolic disease.
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Any clinically significant abnormality or abnormal laboratory test results found
during medical screening which, at the investigator's discretion, warrants exclusion
or positive test for hepatitis B, hepatitis C, or HIV.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
IDT CMAX - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
eXIthera Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
IDT CMAX Clinical Trials
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Syneos Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/Industry
Name [3] 0 0
CPR Pharma Services Pty Ltd, Australia
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02914353
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sepehr Shakib, MD
Address 0 0
IDT CMAX
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications