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Trial registered on ANZCTR


Registration number
ACTRN12616001165471
Ethics application status
Approved
Date submitted
28/07/2016
Date registered
26/08/2016
Date last updated
15/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A First in Human study in ascending doses of FDY-5301.
Scientific title
A Phase I, Ascending Dose Randomized, Blinded, Placebo-Controlled, Single-Center Study to evaluate the safety and tolerability of of Intravenous FDY-5301 in healthy volunteers
Secondary ID [1] 289728 0
None
Universal Trial Number (UTN)
U1111-1185-6171
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
acute myocardial infarction 299572 0
Condition category
Condition code
Cardiovascular 299543 299543 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ascending dose randomized, blinded, placebo-controlled study involving 5 dosing cohorts of FDY-5301 with 8 participants per cohort. Within each dosing cohort, 6 participant will received FDY-5301 and 2 participants will receive placebo.
Doses being investigated are 0.1 mg/kg. 0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, and 10.0 mg/kg.

Both FDY5301 and placebo will be administered as single intravenous infusion.

As this is an in-patient study, only qualified site staff will be administering FDY5301 or placebo and will monitor compliance by noting when the infusion starts and stops.
Intervention code [1] 295366 0
Treatment: Drugs
Comparator / control treatment
Normal saline
Control group
Placebo

Outcomes
Primary outcome [1] 299020 0
To evaluate the safety and tolerability of a single iv dose of FDY-5301 administered to healthy participants.

Safety and tolerability measurements include:
physical examination
vital signs, including monitoring of blood pressure and heart rate
clinical laboratory results (haematology, clinical chemistry, coagulation parameters, urinalysis
ECG
Adverse events

Even though the active ingredient in FDY-5301 has been administered to humans before, the risks associated with intravenous FDY-5301 administration are unknown.

Similar compounds have been administered to humans orally and topically (onto the skin) and the side effects associated with this are impaired thyroid function and skin sensitivity/ reactions. Other possible side effects include: swelling of the salivary glands, nausea, vomiting, diarrhoea, stomach ache, fever, headache, metallic taste, and allergic reactions. Every participant’s clinical signs and symptoms will be monitored closely for these effects throughout the study.

The following will be monitored to assess any adverse effects:
physical examination
vital signs, including monitoring of blood pressure and heart rate
clinical laboratory results (haematology, clinical chemistry, coagulation parameters, urinalysis, thyroid function testing)
ECG
Timepoint [1] 299020 0
Safety and tolerability will be assessed at day of admission, pre-dose, post-dose 2, 5, 15 minute, 1, 2, 4, 12, 24 hour, Day 8, and Week3-4.
Secondary outcome [1] 325881 0
To determine plasma iodide to characterize pharmacokinetics .

Pharmacokinetic parameters that will be assessed are Tmax, Cmax, AUC, and half-life
Timepoint [1] 325881 0
Blood sampling for plasma iodide are collected pre-dose, post-dose 2, 5, 15 mins, 1, 2, 4, 12, 24 hours.
Secondary outcome [2] 325882 0
To explore the effects of FDY-5301 on blood biomarkers following 15 minutes of forearm ischemia and reperfusion.

Biomarkers of interest are plasma levels of F2-isoprostanes, fibrinogen, D-dimer, and serum levels of C-reactive protein.
Timepoint [2] 325882 0
Forearm ischemia will be induced by inflating a blood pressure cuff to 200 mg Hg for 15 minutes and deflated 5 minutes after completion of dosing.

Blood sampling for biomarkers are collected relative to time of dose: pre-dose, post-dose 2, 5, 15 mins, 1, 2, 4, 12, 24 hours .
Secondary outcome [3] 326795 0
To determine urine concentrations of iodide at the completion of 24 hour urinary excretion.

The total amount of iodide excreted in urine over 24 hours will be presented as a percentage of dose administered.
Timepoint [3] 326795 0
Urine collection is a 24 hour continuous collection starting immediately post dose until 24 hours post dose. A pre-dose spot urine is collected for baseline comparison. An aliquot is also taken after the 24 hour collection for analysis.

Eligibility
Key inclusion criteria
1) Aged between 18 and 65 years (inclusive).
2) Subjects must be infertile or agree to the use of medically reliable contraceptive methods (i.e. double barrier) for the duration of the study and for 30 days after study completion.
3) Body Mass Index (BMI) 18-30 inclusive.
4) Euthyroid confirmed by thyroid function testing at screening.
5) Adequate venous access for venipuncture and cannulation for drug administration.
6) Fluent in the English language.
7) A creatinine clearance of greater than 75 mL/min
8) In good general health as determined by medical screening.
9) Ability to provide informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Any chronic illness requiring prescription medication.
2) Presence or history of any thyroid disorder or presence of goiter upon examination
3) History of and/or hypersensitivity reaction to iodide or iodide containing drugs
4) Participation in any investigational study within 30 days of Visit 1.
5) Have donated blood (usually 550 mL) within 30 days of study participation
6) The need to take any over-the-counter (OTC) medications or herbal/vitamin supplements for one week prior to the check-in visit, and during the study
7) The need to take any prescription medications for two weeks prior to the check-in visit, and during the study excluding oral contraceptives, or contraceptive implants.
8) Subjects who are unable to abstain from smoking during study confinement.
9) Females not using medically reliable contraceptive methods (i.e. double barrier) or those who are nursing or pregnant
10) Use of food and/or beverages that contain caffeine or other xanthines (e.g. coffee, tea, cola and chocolate) during the 24 hours prior to dose administration and whilst confined at the clinical facility.
11) Regular drinkers of more than four (4) units of alcohol daily or those who have consumed alcohol within 24 hours pre-dose and until study completion.
12) Acute illness requiring treatment within 30 days of study entry.
13) Any history of clinically significant chronic illness including heart failure, renal failure, or liver disease
14) Have a predisposing condition that might interfere with the absorption, distribution, metabolism, and/or excretion of drugs.
15) Have a history of abnormal bleeding tendencies.
16) History of Hepatitis B, Hepatitis C, acute or chronic hepatitis, or history/demonstration of Human Immunodeficiency Virus (HIV) antibodies or AIDS
17) Current history of alcohol or drug abuse (licit or illicit); or positive urine drug and alcohol screen at screening and pre-dose
18) Have blood pressure readings (after resting for 5 minutes) outside a systolic blood pressure range of 90-140 mmHg or a diastolic blood pressure outside a range of 40-90 on two consecutive measurements
19) Have any evidence of organ dysfunction, or any deviation in clinical laboratory values which is confirmed on re-examination to be clinically significant (i.e. in the opinion of the investigator would jeopardize the safety of the subject or impact the validity of the study results).
20) Inability to provide informed consent.

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)
A total of 40 participants will be enrolled into 5 cohorts. Each cohort has 8 participants with 6 randomized to received FDY-5301( cohort 1 :0.1 mg/kg; cohort 2 : 0.3 mg/kg; cohort 3: 1.0 mg/kg; cohort 4: 3.0 mg/kg; cohort 5: 10 mg/kg) and 2 participants to receive placebo.

A randomisation list will be generated by an unblinded statistician at CNS and will be transferred electronically to the Investigational Site prior to enrolment.

Eligible participants enrolled into the study will be assigned a randomisation number by the Nucleus Network unblinded pharmacist in accordance with the randomization list generated by CNS. The Randomisation List details the randomisation numbers and the associated treatment.

Each participant will receive the treatment which corresponds to their randomisation number (as assigned in the Randomisation List).

The Randomisation List will be available only to pharmacy staff preparing the drug who are not involved in any other aspect of the study. The Randomisation List will not be made available to the Sponsor, subjects, or members of the staff responsible for the monitoring and evaluation of safety assessments (i.e. all blinded study members) until study completion and database lock, unless a full unblinding of the study is required.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The generation of the Randomisation List for each cohort will be performed by a CNS Unblinded Biostatistician using the computer program SAS (registered trademark) v9.4 or later.
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
Safety
Statistical methods / analysis
No formal sample size calculation was performed since no formal hypothesis testing is being conducted.

Demographics will be tabulated and summarized by descriptive statistics (mean, median, standard deviation, range) for continuous data and frequency tables for discrete data. Physical examination data from baseline and post-study and medical history data at baseline will be listed. All clinical safety and tolerability data will be listed for each subject. Laboratory values will be calculated as group mean data and presented in shift tables. Comments as to the clinical significance of out of range values will be listed separately. Adverse event data will be summarized by group, visit, severity, and possible relationship to the IMP. All adverse events reported in this study will be coded using MedDRA 18.1
Standard pharmacokinetic parameters will be calculated for blood iodide levels, and the total amount of iodide excreted in urine over 24 hours will be presented as a percentage of the dose administered.
Levels of biomarkers over time will be tabulated and presented graphically as group mean data over time.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/08/2016
Actual
30/08/2016
Date of last participant enrolment
Anticipated
10/10/2016
Actual
10/10/2016
Date of last data collection
Anticipated
19/10/2016
Actual
19/10/2016
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6236 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 13657 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 294116 0
Commercial sector/Industry
Name [1] 294116 0
Faraday Pharmaceuticals Australia Pty Ltd
Country [1] 294116 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services Pty Ltd
Address
L4, 88 Jephson Street
Toowong, QLD 4066
Country
Australia
Secondary sponsor category [1] 292945 0
Commercial sector/Industry
Name [1] 292945 0
Faraday Pharmaceuticals Australia Pty Ltd
Address [1] 292945 0
C/o Deloitte
L25 Riverside Cntre
123 Eagle Street
Brisbane, QLD 4000
Country [1] 292945 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295522 0
Alfred Health Human Ethics Committee
Ethics committee address [1] 295522 0
Ethics committee country [1] 295522 0
Australia
Date submitted for ethics approval [1] 295522 0
06/07/2016
Approval date [1] 295522 0
09/08/2016
Ethics approval number [1] 295522 0
318/16

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67610 0
Dr Jason Lickliter
Address 67610 0
Nucleus Network
L5, Burnet Building, AMREP Precinct
89 Commercial Road
Melbourne, VIC 3004
Country 67610 0
Australia
Phone 67610 0
+61 3 9076 8900
Fax 67610 0
+61 3 9076 8911
Email 67610 0
[email protected]
Contact person for public queries
Name 67611 0
Lori Seigel
Address 67611 0
Faraday Pharmaceuticals, Inc.
1616 Eastlake Ave E, Suite 560
Seattle, WA 98102
Country 67611 0
United States of America
Phone 67611 0
+1 206 492 5320
Fax 67611 0
Email 67611 0
[email protected]
Contact person for scientific queries
Name 67612 0
Simon Tulloch
Address 67612 0
Faraday Pharmaceuticals, Inc.
1616 Eastlake Ave E, Suite 560
Seattle, WA 98102
Country 67612 0
United States of America
Phone 67612 0
+1 206 492 5310
Fax 67612 0
Email 67612 0
[email protected]

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