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Trial registered on ANZCTR


Registration number
ACTRN12619001762145
Ethics application status
Approved
Date submitted
3/12/2019
Date registered
11/12/2019
Date last updated
11/12/2019
Date data sharing statement initially provided
11/12/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
An interventional study to evaluate the effects of dosages on the Pharmacokinetics (PK, the measure of how the human body processes a substance), Tolerability (how well a substance is tolerated by participants), and Safety of different dosages of Amphotericin B (iCo-019) when given to healthy participants as multiple oral doses.
Scientific title
A Phase 1b, Single-Center, Double-Blind, Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of 100 mg and 400 mg Oral Amphotericin B (iCo-019) or Placebo Administered for 10 Days in Healthy Subjects
Secondary ID [1] 299984 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fungal infection 315456 0
Condition category
Condition code
Infection 313755 313755 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
iCo-019 (oral Amphotericin B) 100mg gelatin capsule taken orally.
Cohort 1: 1 x 100 mg capsule or 1x placebo capsule for 10 days once per day
Cohort 2: 4 x 100 mg capsule or 4x placebo capsule for 10 days once per day

A Safety Evaluating Committee (SEC) will review data from the first cohort (100 mg of oral Amphotericin B or placebo) once completed and make a recommendation whether it is safe to proceed with multiple dosing of 400 mg of oral Amphotericin B or placebo in the second cohort.
Adherence to the study treatments will be monitored by inpatient stay and observation; participants in will be confined to the study unit from check-in on Day -1 through to
discharge at 48-hour post last dose.
Intervention code [1] 316255 0
Treatment: Drugs
Comparator / control treatment
The placebo capsules will be composed of the same inactive ingredients (excipients only) used in the IP formulation.
Control group
Placebo

Outcomes
Primary outcome [1] 322165 0
To evaluate safety and tolerability after repeated administration of 100 mg and 400 mg doses of oral Amphotericin B (iCo-019) for 10 days in healthy subjects
This will be assessed by looking at the incidence, severity, causality, and seriousness of adverse events;
changes in clinical laboratory evaluations; changes in vital signs parameters, and ECGs; changes in physical examination findings.
Possible adverse events (based on common side effects of IV formulation of Amphotericin B) include: nausea, rash, mild headache.
Timepoint [1] 322165 0
Adverse event information will be recorded from the time of admission to the study unit until 10 days after the last dose of study drug.
Clinical laboratory evaluations of serum chemistry, hematology, urine chemistry and urinalysis will be performed at Screening, Check-in (Day -1), pre-dose on Days 2, 5, 7 and 10; at Discharge from clinic (48 hours post last dose); at Follow-up (Day 12) and End of Study (Day 20)/Early Withdrawal.
Vital signs, including blood pressure, pulse rate, respiratory rate and oral temperature will be measured at Screening; Check-in (Day -1); Pre-dose, and 2 hours post-dose on Day 1.
Blood pressure and heart rate will be measured Pre-dose, and 2 hours post-dose on Days 2, 5, 7, and 10; at Discharge from clinic (48 hours post last dose); at Follow-up (Day 12) and End of Study (Day 20)/Early Withdrawal.
12-lead ECGs will be obtained at: Screening; Check-in (Day -1); Pre-dose on Day 1; 2 hours postdose on Days 5, 7, and 10; at Discharge from clinic (48 hours post last dose); at Follow-up (Day 12) and End of Study (Day 20)/Early Withdrawal.
Secondary outcome [1] 377554 0
To evaluate pharmacokinetic profile after repeated administration of oral Amphotericin B (10 days) in healthy individuals.
Blood samples will be collected and the following PK parameters will be assessed in plasma-
Peak concentration (Cmax)
Time to peak concentration (Tmax)
terminal elimination rate constant (Kel)
half-life (t1/2)
Area under the concentration-time curve from time 0 to the last measurable concentration timepoint
(AUC0-t)
Area under the concentration-time curve from time 0 and extrapolated to infinity (AUC0-infinity)
area under the concentration-time curve from time 0 to 24 hours (AUC0-24)
Timepoint [1] 377554 0
Blood samples for PK will be collected at the following timepoints:
Pre-dose, and 2, 4, 6, 8, 10, 12, and 24 hours post- dose on Days 1 and 10
Pre-dose on Days 2, 5 and 7.
Day 11 (36 hours post last dose)
Day 12 (48 hours post last dose)
Day 15
Day 20

Eligibility
Key inclusion criteria
1. Healthy subjects as demonstrated by physical examination, medical history and overall assessment by the Investigator, in consultation with the medical monitor (if required)
2. Adult male or female volunteers, aged 18-55 years inclusive
3. BMI of 18.0 kg/m2 to 30.0 kg/m2
4. Not taking any prescription medication (with the exception of hormonal contraceptives for women of child-bearing potential [WOCBP]) within 14 days prior to study drug administration until 10 days after dosing; no use of Over-the-counter (OTC) medication (including paracetamol), or herbal and dietary health products within 48 hours prior to study drug administration until 10 days after dosing. Coated paracetamol may be used at the discretion of the investigator (or delegate).
5. Women who are postmenopausal for 1 year or more (post-menopausal is defined as documented amenorrhea for at least 1 year with an FSH >/= 40 mIU/ml if menses has occurred within 2 years); women who are surgically sterilized; WOCBP who are nonlactating and using a highly effective form of birth control during the course of the study and for 30 days after the treatment period (i.e. established use of oral, injected, or implanted hormonal methods of contraception in combination with a barrier method; placement of an intrauterine device (IUD) or intrauterine system (IUS) in combination with a barrier method; sterilized male partner (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate) in combination with a barrier method; true abstinence) and have a negative beta-HCG result (human chorionic gonadotropin in serum or urine) at screening and check-in at Day-1.
6. Male subjects must agree to practice abstinence; be surgically sterilized; or use a medically acceptable method of contraception/birth control if they have a female partner of child-bearing potential, as well as having the female partner use an effective form of contraception, throughout the study duration and for 90 days after the study is completed. Male participants must refrain from sperm donation for the purposes of conception while enrolled in this study and for a period of 3 months (the approximate duration of spermatogenesis) following drug exposure
7. Able to read and understand the Informed Consent Form
8. Willing to participate in the study
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any medical condition or prior therapy that, in the opinion of the investigator and in consultation with the medical monitor (if required), would make the subject unsuitable for this study
2. Inability to swallow capsules
3. Pregnant or breastfeeding, or planning to conceive until at least 30 days after the administration of Investigational Product
4. Surgery within the previous 3 months (except for minor cosmetic or dental procedures)
5. Symptoms of a clinically significant illness (eg, gastrointestinal illness, infection such as influenza, upper respiratory tract infection) in the four weeks before the study drug dosing that, in the opinion of the Investigator, may influence the outcome of the study
6. Average weekly alcohol intake that exceeds 21 units per week (males) or 14 units (females) per week, or are unwilling to stop alcohol consumption for 2 days prior to study drug dosing until 10 days after dosing (one unit is equivalent to a half-pint (285 mL) of beer or 1 (25 mL) measure of spirits or 1 glass (125 mL) of wine).
7. Positive alcohol breathalyzer test at screening or check-in at Day-1
8. Positive urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, cotinine) at screening or check-in at Day-1
9. Use of more than 4 tobacco- or nicotine-containing products per month within 6 months prior to first study dose, or unwilling to refrain from the use of such products from Screening until completion of the final study visit;
10. Lactose intolerance or other gastrointestinal disease that in the opinion of the Investigator and in consultation with the medical monitor (if required), may alter the amount and rate of drug absorption (e.g. diarrhea, IBS, Celiac disease)
11. Any serious medical condition; e.g., kidney, liver or cardiac disease (outside standard range of results), asthma, diabetes, thyroid disease, angioedema, hypertension, bleeding disorder, malignancy, seizure, neutropenia, AIDS, etc.
12. Any condition, occupational reason or other responsibility that, in the judgment of the Investigator, would jeopardize the safety or rights of a volunteer, or render the subject unable to comply with the protocol
13. Participation in another clinical trial and/or treatment received with any investigational agent within one month before the initial dose of study medication
14. 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 follow-up visits on schedule.

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)
Allocation involves contacting the holder of the allocation schedule who is the off-site pharmacist with no contact with participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised 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
Intervention assignment
Other
Other design features
Participants will be assigned to different dosages and treatments depending on which study cohort they are enrolled into.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Total enrollment of healthy adult subjects in the planned two dose cohorts approximately 12 (6 subjects/cohort; 5:1 active:placebo). The sample size for this study is based on
clinical and practical considerations and not on a formal statistical power calculation.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
9/12/2019
Date of last participant enrolment
Anticipated
14/01/2020
Actual
Date of last data collection
Anticipated
2/02/2020
Actual
Sample size
Target
12
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 15384 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 28701 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 304443 0
Commercial sector/Industry
Name [1] 304443 0
iCo Therapeutics Inc
Country [1] 304443 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
iCo Therapeutics Inc
Address
6th Floor – 777 Hornby Street
Vancouver, BC V6Z1S4
Country
Canada
Secondary sponsor category [1] 304709 0
None
Name [1] 304709 0
Address [1] 304709 0
Country [1] 304709 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304877 0
Bellberry Limited
Ethics committee address [1] 304877 0
129 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 304877 0
Australia
Date submitted for ethics approval [1] 304877 0
09/10/2019
Approval date [1] 304877 0
08/11/2019
Ethics approval number [1] 304877 0
2019-10-859

Summary
Brief summary
This research project is being conducted to look at the safety, tolerability and pharmacokinetics (PK, how the human body processes a substance) of iCo-019 (oral Amphotericin B when given to healthy volunteers as multiple oral doses for to 10 consecutive days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98502 0
Dr Jasmine Williams
Address 98502 0
Linear Clinical Research
Level 1, B Block, QEII Medical Centre, Hospital Avenue
Nedlands Western Australia 6009
Country 98502 0
Australia
Phone 98502 0
+61 8 63825100
Fax 98502 0
Email 98502 0
[email protected]
Contact person for public queries
Name 98503 0
Jasmine Williams
Address 98503 0
Linear Clinical Research
Level 1, B Block, QEII Medical Centre, Hospital Avenue
Nedlands Western Australia 6009
Country 98503 0
Australia
Phone 98503 0
+61 8 63825100
Fax 98503 0
Email 98503 0
[email protected]
Contact person for scientific queries
Name 98504 0
Jasmine Williams
Address 98504 0
Linear Clinical Research
Level 1, B Block, QEII Medical Centre, Hospital Avenue
Nedlands Western Australia 6009
Country 98504 0
Australia
Phone 98504 0
+61 8 63825100
Fax 98504 0
Email 98504 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
individual participant data underlying published results only
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
only to achieve the aims in the approved proposal
How or where can data be obtained?
access subject to approvals by sponsor, iCo Therapeutics Ltd.
Contact iCo Chief Medical Officer Peter Hnik [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
6004Clinical study report  [email protected]



Results publications and other study-related documents

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