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Trial registered on ANZCTR


Registration number
ACTRN12618000364279
Ethics application status
Approved
Date submitted
5/03/2018
Date registered
9/03/2018
Date last updated
25/11/2019
Date data sharing statement initially provided
25/11/2019
Date results information initially provided
25/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase I study to investigate pharmacokinetics, safety, and tolerability of two single doses of EU-C-001 given as slow intravenous infusions in healthy female subjects
Scientific title
A Phase I study to investigate pharmacokinetics, safety, and tolerability of two single doses of EU-C-001 given as slow intravenous infusions in healthy female subjects
Secondary ID [1] 294231 0
Nil known
Universal Trial Number (UTN)
U1111-1210-2771
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic brain injury 306900 0
Condition category
Condition code
Neurological 305993 305993 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Female subjects will receive two single 30-minute intravenous infusions of the study medication EU-C-001, the first an intravenous infusion of 15 mg EU-C-001 and after a wash-out of at least seven days an intravenous infusion of 90 mg EU-C-001.
Intervention code [1] 300526 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305031 0
Determining the safety and tolerability of two single doses of EU-C-001 given as a slow intravenous infusions by measuring the following:
- Vital signs :blood pressure & pulse rate
- ECG
- Physical examination
- Laboratory tests: Biochemisrty, haematology and urinalysis
-Assessment of adverse events
Timepoint [1] 305031 0
monitoring after start of infusion:
-Vital signs :at 1h, 2h, 4h, 12h, 16h, and 24h
- ECG: 1h, 2h, 4h, 12h, and 24h
- Physical examination : 24 hrs
- Laboratory tests: 24 hrs
-Assessment of adverse events : on an ongoing basis to end of study on day 17
Secondary outcome [1] 343922 0
Determining the pharmacokinetics of two single doses of EU-C-001 given as a slow intravenous infusions by measuring the pharmacokinetics in plasma and urine.

The pharmacokinetic parameters of EU-C-001 and Desmethyl-EU-C-001
measured in plasma are:
AUC0?t , AUC0-inf, Cmax, tmax, ?z , and t1/2 ,.
The pharmacokinetic parameters for EU-C-001 and for Desmethyl-
EU-C-001 in urine are (Ae0-t).
Timepoint [1] 343922 0
Pharmacokinetics in plasma: 0.25h (15 minutes), 0.5h (30 minutes = end of infusion), 0.67h (40 minutes), 0.83h (50 minutes), 1.0h, 1.25h, 1.5h, 2.0h, 2.5h, 3.0h, 3.5h, 4.0h, 5.0h, 6.0h, 7.0h, 8.0h, 10h, 12h, 15h, 24h, 36h, 48h, and 72h after start of the EU-C-001 infusion. Assay: LC-MS/MS.
Pharmacokinetics in urine: urine will be collected quantitatively during the following time intervals: 0h-4h, 4h-8h, 8h-12h, 12h-24h, 24h-36h. Assay: LC-MS/MS.

Eligibility
Key inclusion criteria
1. Gender Female
2. Age: Between 18 and 45years
3. Weight: 50.0–85.0 kg
4. BMI: 19.0–28.0 kg/m2
5. Medical history without clinically relevant pathologies
6. Physical examination parameters without signs of clinically relevant pathologies
7. Electrocardiogram recording without signs of clinically relevant pathology, in particular QTc (Bazett) <450 ms
8. Values for hematology and for biochemistry tests of blood and urine within the normal range or showing no clinically relevant deviation as judged by the medical investigator (in particular normal values for ALAT, ASAT, LDH, gamma-GT, alkaline phosphatase, and bilirubin)
9. For three weeks before the first drug administration and until one month after participation in the study, subjects of childbearing potential must be willing to practice a medically approved highly effective birth control method (e.g., condom in combination with a) hormonal contraception, b) intrauterine device (IUD), or c) intrauterine hormone-releasing system (IUS); sexual abstinence; or has a partner being vasectomized since > 6 months)
10. Having given written informed consent before any study-related activities are carried out
11. Negative serum pregnancy test
Minimum age
18 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Being pregnant or breast feeding
2. Evidence of clinically relevant pathology or disease
3. Evidence of moderate or severe hypertension, hypotension or orthostatic hypotension (fall in systolic blood pressure of >20 mmHg on standing up from supine)
4. Unwilling and/or incapable of giving informed consent
5. Having had any previous traumatic brain injury, concussion or unexplained loss of consciousness
6. Any history of clinically important psychiatric illness eg history of depression treated with antidepressant or of any clinically important neurological or neuro-muscular disorders and/or epilepsy
7. Acute or chronic gastrointestinal disorders
8. Presence or history of endocrine disorders
9. Known hypersensitivity to the study drug or constituent of the study drug
10. History of immediate hypersensitivity to any drug,
11. Strict vegetarian or vegan
12. Regular treatment with medications during three months prior to screening (except hormonal contraception or replacement)
13. Receipt of any prescription or non-prescription medication, complementary therapies including multi-vitamin preparations within 14 days prior to the day of the first pharmacokinetic assessment and for the duration of the study with the exception of paracetamol at a dose less than or equal to 2g per day
14. Participation in a clinical study within 90 days prior to randomization or within 7 half-lives of a previous investigational agent
15. Having already received EU-C-001
16. Donation of blood within 90 days prior to screening
17. Receipt of blood, blood products or plasma derivatives one year prior to screening
18. History of use of tobacco or nicotine-containing products within the past three months
19. Any history of alcohol abuse or drug addiction
20. Positive results at screening for drugs of abuse (Methamphetamines / Opiates / Cocaine / Cannabinoids / Phencyclidine / Benzodiazepines / Barbiturates / Methadone / Tricyclic Antidepressants / Amphetamines) or alcohol (breath test) at screening or on admission
21. Positive screen results for HBsAg (except for subjects vaccinated for hepatitis or subjects with past but resolved hepatitis), anti-HCV, or anti-HIV1&2
22. Consumption of abnormal quantities of coffee or tea or other caffeinated drinks (i.e., more than 5 cups per day [1 cup = 150 ml])
23. Any disease which in the Investigator’s opinion would exclude the subject from the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Adverse events will be listed per dose, subject and medication and
analyzed by intensity and relationship to study drug formulation and
dose. All other safety and tolerability parameters will be presented
descriptively.
Only a descriptive statistical approach will be used for pharmacokinetics.

Recruitment
Recruitment status
Completed
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 postcode(s) [1] 21923 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 298870 0
Commercial sector/Industry
Name [1] 298870 0
PresSura Neuro
Address [1] 298870 0
470 Collins Street, Suite 3, Level 2
Melbourne 3000, Victoria, Australia
Country [1] 298870 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
PresSura Neuro
Address
470 Collins Street, Suite 3, Level 2
Melbourne 3000, Victoria, Australia
Country
Australia
Secondary sponsor category [1] 298077 0
None
Name [1] 298077 0
None
Address [1] 298077 0
None
Country [1] 298077 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299811 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 299811 0
129 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 299811 0
Australia
Date submitted for ethics approval [1] 299811 0
10/01/2018
Approval date [1] 299811 0
06/02/2018
Ethics approval number [1] 299811 0
2017-12-964

Summary
Brief summary
This is a phase 1 study in healthy subjects. It is planned to develop the drug for reducing pressure in the brain of patients with a traumatic brain injury (TBI). Increased pressure following TBI can lead to death or can cause permanent disability. There are currently no medications that are approved for improving outcomes after TBI. The drug will also be tested for improving clinical outcome in patients that suffered a concussion.
The study drug being evaluated is called EU-C-001 and is being developed by an Australian company called PresSura Neuro. Studies in animals have shown that EU-C-001 may reduce pressure in the brain. Therefore, it is thought that EU-C-001 may improve outcomes in patients with TBI by increasing the amount of oxygen available to brain tissue. In other studies it was shown that the EU-C-001 may also have potential to improve outcomes in patients with concussion.
Single oral administrations up to 180 mg EU-C-001 and single intravenous administrations up to 90 mg EU-C-001 have been administered to healthy male subjects. The safety, tolerability and pharmacokinetic information is not yet available in females. Therefore, the present study is planned to investigate the safety, tolerability and the pharmacokinetic characteristics of the medication given intravenously in healthy female subjects and will compare the result from a historical data set obtained from studies in healthy male subjects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81638 0
Dr Thomas Polasek
Address 81638 0
CMAX Clinical Research
Level 5, 18a North Terrace
Adelaide, SA, 5000, Australia
Country 81638 0
Australia
Phone 81638 0
+61 8 7088 7900
Fax 81638 0
Email 81638 0
Thomas.Polasek@cmax.com.au
Contact person for public queries
Name 81639 0
Mr Peter Pursey
Address 81639 0
PresSura Neuro
470 Collins Street, Suite 3, Level 2
Melbourne 3000, Victoria, Australia
Country 81639 0
Australia
Phone 81639 0
(+61) 400 414 416
Fax 81639 0
Email 81639 0
info@pressuraneuro.com
Contact person for scientific queries
Name 81640 0
Prof Klaus Kutz
Address 81640 0
AccelPharm
Hebelstrasse 15A, 4056 Basel, Switzerland
Country 81640 0
Switzerland
Phone 81640 0
(+41) 61 273 55 44
Fax 81640 0
Email 81640 0
klaus.kutz@bluewin.ch

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 that underlie the results reported in the primary journal article containing the study results, after deidentification (text, tables, figures, appendices).
When will data be available (start and end dates)?
Beginning 6 months and ending 5 years following publication of the primary journal article containing the study results
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
To achieve aims in the approved proposal
How or where can data be obtained?
Proposals should be directed to info@pressuraneuro.com. To gain access, data requestors will need to sign a data access agreement.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary