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Trial registered on ANZCTR


Registration number
ACTRN12618000195257
Ethics application status
Approved
Date submitted
22/12/2017
Date registered
7/02/2018
Date last updated
3/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single-Center, Randomized, Double-Blind, Placebo Controlled, Multiple-Dose, Dose Escalation Study to Evaluate the Safety/Tolerability and Pharmacokinetics of FP-045 Administered Orally to Normal, Healthy Volunteers
Scientific title
A Single-Center, Randomized, Double-Blind, Placebo Controlled, Multiple-Dose, Dose Escalation Study to Evaluate the Safety/Tolerability and Pharmacokinetics of FP-045 Administered Orally to Normal, Healthy Volunteers
Secondary ID [1] 293568 0
FP045C-17-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral arterial disease 305802 0
Condition category
Condition code
Cardiovascular 305022 305022 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 3 cohorts of Normal Healthy Volunteers (NHV) will be enrolled with sentinel dosing in each cohort. Subjects in each cohort will be randomized to orally receive either FP-045 (6 subjects) or placebo (2 subjects) at doses and intervals as presented below:

Active treatment will be FP-045 (powder for oral solution) for reconstitution in cranberry juice and delivered as 120 mL oral solution total dosing volume per subject's cohort.

Cohort 1 will receive 120 mg daily oral dose of FP-045 or Placebo for 7 days.
Cohort 2 will receive 250 mg daily oral dose of FP-045 or Placebo for 7 days.
Cohort 3 will receive 500 mg daily oral dose of FP-045 or Placebo for 7 days.

All subjects will remain in the Clinical Research Unit (CRU) for observation until completion of all assessments on Day 10.

Dosing will take place in the morning on dosing days under the supervision of study staff.
Study drug compliance will be documented in the eCRF by recording:
The date and time of each oral administration,
The volume of each oral dose administered,
Whether or not the entire amount of each oral dose of FP-045 was administered and whether or not subject vomited after administration of the dose.
Intervention code [1] 299814 0
Treatment: Drugs
Comparator / control treatment
The placebo will be cranberry juice delivered as an oral solution that is identical to FP 045, but without FP-045.
Control group
Placebo

Outcomes
Primary outcome [1] 304185 0
To evaluate the safety/tolerability of multiple escalating doses of FP-045 administered orally to NHVs. Safety will be measured by routine clinical and laboratory procedures, physical examination, collection of vital signs and ECGS, and recording of treatment-emergent AEs and SAEs. Consistent with first in human clinical trials, sentinel dosing of each Cohort 1-3 will be conducted. Dose Escalation Safety Reviews - Prior to each dose level adjustment (following administration of the Day 7 dose in the final subject in each cohort), the clinical and laboratory safety parameters from the previous dosing cohort will be reviewed by the Safety Review Committee (SRC) (in a blinded fashion) to permit a decision on whether or not to advance to the next higher dose level. The suggested next doses may be decreased based on evaluation of safety, tolerability, and PK data observed in previous treatment cohorts.
Timepoint [1] 304185 0
Following enrollment into the study and administration of the 1st dose of study drug subjects will undergo vital sign measurements and physical examinations on Days 1 through 10 and at End of Study/Day 14 (EOS), as well as clinical laboratory tests (chemistry, hematology, APTT, INR and urinalysis) on Day1 through 7 and on Day 10 and EOS/Day14. A 12-lead ECG will be performed before first dose and 30 minutes, 1.5 hour and 4 hour post daily dose on Days 1, 2, 7 and EOS/Day14. Concomitant medications will be recorded from dosing with study drug through EOS/Day14. Evaluation of safety by the safety review committee (SRC), including the opinion of the Investigator and Sponsor’s medical monitor, will be used in evaluating safety data to determine a maximum tolerated dose (MTD). Adverse events will be assessed from the time of informed consent through EOS/Day14.
Secondary outcome [1] 341161 0
To estimate the PK profiles of prodrug FP-045 (and active AD-835) after multiple, escalating oral doses of FP-045 administered to NHVs. The blood concentrations of the study drugs will be listed and summarized with the number of observations, mean, geometric mean, standard deviation, median, maximum, and coefficient of variation (CV). Figures displaying blood concentrations over time as well as non-compartmental PK parameters for the study drugs will be estimated and summarized: AUC0-24, AUC0-24(Day 7)/AUC0-24(Day1), Cavg, Cmax, Tmax, t1/2, lambda z, CL/F, and Vz/F.
Timepoint [1] 341161 0
Sampling for PK analysis will occur predose on Day 1 (within 30 minutes before dosing) and 0.25 hr, 0.5hr, 0.75hr, 1 hr, 1.5 hr, 2hr, 4 hr, 6hr, 8 hr, 12 hr, and 16 hr postdose. Sampling for PK analysis will occur predose on Days 2 and 5 (within 30 minutes before dosing). Sampling for PK analysis will occur at 24hr, 36 hr, 48 hr, 72 hr and 96hr post Day 7 dose. Sampling for PK analysis will occur at Day 14/EOS.

Eligibility
Key inclusion criteria
1. Male or female NHV, age 18 to 55 years, inclusive (at the time of informed consent).
2. Females must be either postmenopausal for greater than or equal to 1 year (or with FSH greater than or equal to 40 mIU/mL if postmenopausal for less than 1 year) or surgically sterile (having undergone bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 6 months.
3. Males with female partners of childbearing potential must agree to use barrier contraceptive (i.e., condom) and their female partners must use a highly effective method of contraception from Screening through 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period. Males who are abstinent will not be required to use a contraceptive method unless they become sexually active.
4. The subject is, in the opinion of the Investigator, generally healthy based on assessment of medical history, physical examination, vital signs, electrocardiogram (ECG), and the results of the hematology, clinical chemistry, urinalysis, serology, and other laboratory tests.
5. Baseline laboratory test values within reference ranges based on the blood and urine samples taken at Screening and on Day -1 (before administration of the initial study drug). Out of normal ranges values may be accepted by the Investigator, if not clinically significant.
6. Nonsmoker and/or ex-smoker who has discontinued smoking and/or use of nicotine containing products for at least 6 months prior to the first dose of study drug
7. Body mass index between 18 and 30 kg/m2, inclusive.
8. Written informed consent obtained.
9. Ability to communicate well with the Investigator, in the local language, and to understand and comply with the requirements of the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of any clinically significant neurological, metabolic, gastrointestinal, endocrinological (in particular diabetes or pre-diabetes), cardiovascular, hematological, hepatic, immunological, renal, respiratory, chronic infections, psychiatric, or genitourinary abnormalities or diseases. Note: NHVs with a history of uncomplicated kidney stones or asthma may be enrolled in the study at the discretion of the Investigator.
2. History of malignant neoplastic disease, with the following exceptions:
a. Adequately treated non-melanomatous skin carcinoma
b. Female with a history of benign cervical carcinoma neoplasia if compliant with surveillance and treatment as recommended by her physician
3. Mentally or legally incapacitated, has significant emotional problems at Screening or expected during the conduct of the study, or has a history of a clinically significant psychiatric disorder within the last 5 years. Note: NHVs who have had situational depression may be enrolled in the study at the discretion of the Investigator.
4. The subject has a history of severe drug allergy or hypersensitivity or food allergy, including anaphylaxis.
5. The subject has had surgery or trauma with significant blood loss within the last 3 months prior to the first dose of study drug.
6. The subject has donated more than 1 unit (500 mL) of blood with 4 weeks prior to the first dose of study drug.
7. Fever (body temperature greater than 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening.
8. Blood pressure greater than 140/90 mm Hg or heart rate greater than 100 beats per minute at Screening or at Day 1. Vitals may be repeated up to 2 times for the purpose of eligibility.
9. Clinically significant laboratory abnormalities including:
a. Impaired renal function (serum creatinine levels greater than 1.2 mg/dL) at Screening; estimated creatinine clearance (CrCl) of less than 80 mL/minute
b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) laboratory values greater than 1.2 × upper normal limits
10. Clinically significant abnormality on ECG performed at Screening or prior to administration of the first dose of study drug. (Screening ECG conduction intervals must be within gender specific normal ranges [QT interval corrected for heart rate [QTc] males less than or equal to 450 msec and females less than or equal to 470 msec].)
11. Positive test for hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus antibody at Screening
12. Positive screen for drugs with a high potential for abuse (amphetamine, cannabinoid, cocaine, morphine, and phencyclidine) at Screening and Study Day -1.
13. Consumed food or drink containing grapefruit juice within 72 hours before start of dosing or expected to do so through Study Day 14 End of Study/Early Termination.
14. Consumed alcohol within 72 hours before start of dosing through Study Day 14 End of Study/Early Termination.
15. Received any previous FP-045 or has taken any investigational product within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
16. Female who is breastfeeding or has a positive pregnancy test
17. Unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject’s return for the scheduled EOS Visit
18. The subject has taken prescription medications within 2 weeks (or within 5 half-lives, whichever is longer) or nonprescription medication, herbal remedies, vitamins or minerals within 1 week prior to the administration of the first dose of study and continuing throughout the study until the final study visit. Note: There may be certain medications that are permitted at the discretion of the Investigator and Sponsor (including paracetamol/ acetaminophen, which may be used for minor ailments during the course of the study without prior consultation with the Sponsor’s Medical Monitor).
19. The subject exercises extensively (e.g. marathon, triathlon or other similar high energetic sports). In general, subjects should refrain from sporting from 4 days before participation in the study until the EOS/ET visit.

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)
Copies of the randomization sequence and treatment codes will be kept in the pharmacy at the Clinical Research Unit. Unblinded pharmacy (or other qualified site) personnel will be utilized to prepare the study drug for this trial.

Subjects will receive a 3-digit screening number at the Screening Visit following informed consent and if deemed eligible, a randomization number will be allocated (based on the randomization schedule) at any time from Day -1 to prior to dosing on Day 1. The assignment of number and code for subject identification is based on the obligation for anonymity.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a single center Phase 1 study; the study site’s Pharmacist (or qualified designee) will obtain the study drug assignment from a computer-generated randomization code list, by cohort, using a validated random generator software. The randomization scheme and codes will be generated by an unblinded Statistician and provided to the site prior to study commencement.
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
Other
Other design features
Assignment is ascending dose escalation by cohort
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
This is an exploratory study and therefore, is not powered for inferential statistical analyses. Approximately 24 subjects (18 subjects receiving FP-045, 6 subjects receiving placebo) will be enrolled in this study. The number of subjects was selected to allow sufficient evaluation of safety, tolerability, and PK of the various multiple-dose regimens to be administered in this study and is consistent with standards of practice for Phase 1 studies.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/02/2018
Actual
15/02/2018
Date of last participant enrolment
Anticipated
15/05/2018
Actual
21/05/2018
Date of last data collection
Anticipated
15/06/2018
Actual
23/07/2018
Sample size
Target
24
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9516 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 18264 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 298180 0
Commercial sector/Industry
Name [1] 298180 0
Foresee Pharmaceuticals Co., Ltd.
Country [1] 298180 0
Taiwan, Province Of China
Primary sponsor type
Commercial sector/Industry
Name
Foresee Pharmaceuticals Co., Ltd.
Address
3F., No. 19-3, Sanchong Rd., NanKang District.
Taipei 115, Taiwan
Country
Taiwan, Province Of China
Secondary sponsor category [1] 297278 0
Commercial sector/Industry
Name [1] 297278 0
InClin Pty Ltd
Address [1] 297278 0
210 / 25 BERRY STREET
NORTH SYDNEY. NSW
AUSTRALIA, 2060
Country [1] 297278 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299195 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 299195 0
Ethics committee country [1] 299195 0
Australia
Date submitted for ethics approval [1] 299195 0
11/12/2017
Approval date [1] 299195 0
05/02/2018
Ethics approval number [1] 299195 0

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

Contacts
Principal investigator
Name 79614 0
Dr Jason Lickliter
Address 79614 0
The Nucleus Network Burnet Tower AMREP Precinct 89 Commercial Rd Melbourne VIC 3001
Country 79614 0
Australia
Phone 79614 0
+61 3 9076 8960
Fax 79614 0
Email 79614 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 79615 0
Taylor Kilfoil
Address 79615 0
InClin PTY LTD
210 / 25 BERRY STREET
NORTH SYDNEY. NSW
AUSTRALIA, 2060
Country 79615 0
Australia
Phone 79615 0
+61 408 880 403
Fax 79615 0
Email 79615 0
tkilfoil@inclin.com
Contact person for scientific queries
Name 79616 0
Yisheng Lee
Address 79616 0
Foresee Pharmaceuticals Co., Ltd.
1 Innovation Way, Suite 100, Newark, DE 19711, USA
Country 79616 0
United States of America
Phone 79616 0
+1 408 823 4807
Fax 79616 0
Email 79616 0
Yisheng.Lee@foreseepharma.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseTargeting mitochondrial dysfunction and oxidative stress in heart failure: Challenges and opportunities.2018https://dx.doi.org/10.1016/j.freeradbiomed.2018.09.019
N.B. These documents automatically identified may not have been verified by the study sponsor.