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Trial registered on ANZCTR


Registration number
ACTRN12619001756112
Ethics application status
Approved
Date submitted
4/11/2019
Date registered
10/12/2019
Date last updated
10/12/2019
Date data sharing statement initially provided
10/12/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SIR1-365
Scientific title
A Randomized, Double Blind and Placebo Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SIR1-365 after Oral Administrations in Healthy Volunteers
Secondary ID [1] 299587 0
SIR365-AU-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neurodegenerative disease 314864 0
inflammatory disease 314865 0
Condition category
Condition code
Neurological 313201 313201 0 0
Alzheimer's disease
Neurological 313202 313202 0 0
Parkinson's disease
Neurological 313203 313203 0 0
Other neurological disorders
Inflammatory and Immune System 313204 313204 0 0
Other inflammatory or immune system disorders
Neurological 313205 313205 0 0
Multiple sclerosis
Renal and Urogenital 313206 313206 0 0
Other renal and urogenital disorders
Neurological 313806 313806 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 1 includes 5 dosing cohorts with 8 subjects in each cohort, 6 subjects to be treated with SIR1-365 and 2 subjects with placebo. Two subjects to be enrolled in each of the 5 dosing cohorts will be treated first (one subject with SIR1-365 and another subject with matching placebo). If there is no significant safety concern within 48 hours after dosing in those two subjects, the rest of the subjects in the dose cohort will then be treated at the same time with a single oral dose of either placebo or SIR1-365.
Subjects in cohorts 1-5 will receive a single 10mg, 30mg, 100mg, 200mg or 300mg oral dose of SIR1-365 or placebo instead of SIR1-365. Dose escalation will not occur until a decision is made by the Safety Review Committee based on the review of safety and tolerability data from the previous dose cohort. Each subject will remain in the study unit for 5 days.
Part 2 will include 3 dosing cohorts with 10 subjects in each cohort. Eight subjects will be treated with SIR1-365 and two subjects with placebo in each cohort. Subjects enrolled in the Part 2 2nd cohort, will have one CSF sample collected during Days 5-9.
The three doses for Part 2 will be decided after the completion of Part 1. The potential dose range for Part 2 is 10-300mg.
Each subject will receive oral administrations of either placebo or SIR1-365 to be administered twice daily for 10 days. Each subject will remain in the study unit for 14 days.
All Part 1 and Part 2 subjects will complete 1 additional outpatient visit for safety assessment. Study staff will instruct subjects to take the study medication exactly as instructed as compliance is necessary for subject safety and for the validity of the study.
Intervention code [1] 315841 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet which is an excipient match to the SIR1-365 tablet. The placebo tablet is an uncoated compressed tablet or caplet depending on the dosage.
Control group
Placebo

Outcomes
Primary outcome [1] 321713 0
Safety (e.g., Adverse Events (AE), Serious Adverse Events (SAE), Vital Signs Measurements, 12-lead Electrocardiogram (ECG) Results, Clinical Laboratory Results, Physical Examination Findings).

Clinical Laboratory tests include:
- Blood haematology
- Blood chemistry
- Blood coagulation
- Blood serology (HIV, Hepatitis B and C)
- Urinalysis
- Serum and urine pregnancy test (women of child bearing age)

A complete physical examination will include but not limited to the evaluation of the following organs or body systems: skin; head, eyes, ears, nose, and throat; thyroid; respiratory, cardiovascular, and central nervous systems; abdomen (liver and spleen); lymph nodes; and extremities.
Timepoint [1] 321713 0
Part 1 - Baseline (Day -1) and Days 1, 2, 3, 4 and 11 after intervention. A complete physical examination will be completed at screening (including weight and height), baseline and day 4. All other safety assessments are completed at all scheduled visits including screening, except for the following:
Serum pregnancy (hCG) test: Screening,
Urine pregnancy test: Day -1,
HIV, hepatitis B & C test: Screening

Part 2 - Baseline (Day -1) and Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 and 20 after intervention. A complete physical examination will be completed at screening (including weight and height), baseline and day 13. Vital Signs Measurements will be completed at all scheduled visits including screening. 12-lead Electrocardiogram (ECG) and Clinical Laboratory tests will be completed at screening, baseline and Days 1, 4, 7, 10, 13 and 20 except for the following:
Serum pregnancy (hCG) test: Screening
Urine pregnancy test: Day -1
HIV, hepatitis B & C test: Screening
Primary outcome [2] 321714 0
Pharmacokinetics: The plasma concentration time data for SIR1-365 will be analyzed using non-compartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest include Cmax, Tmax, t1/2, AUClast, AUCinf, CL/F and Vd/F for plasma, when possible. Additional parameters may be estimated and reported, as appropriate.
Timepoint [2] 321714 0
Part 1 Blood: Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12 hours after morning dose.
Days 2-4
Part 1 Urine: pre-dose, 0-4, 4-8, 8-12 and 12-24 hours post dose.
Part 2: Day 1: pre-dose, 0.5, 1, 2, 4, 6, 9, 9.5, 10, 11, 13, 15 and 18 hours after morning dose.
Days 2-9: one sample within 30 min prior to the morning and evening dosing, respectively every day
Days 10-13: pre-dose, 0.5, 1, 2, 4, 6, 9, 9.5, 10, 11, 13, 15, 18, 24, 36, 48, 60 and 72 hours after morning dose on Day 10
Subjects enrolled in the 2nd cohort, will have one CSF sample collected during Days 5-9. A blood PK sample will be collected around 30 minutes after collection of the CSF sample.
Secondary outcome [1] 375994 0
Pharmacodynamics: plasma samples from each subject to be enrolled in one of the cohorts in Part 2 (to be selected after PK data is available) will be used for the measurements of a common cytokine panel and IL-33.
Timepoint [1] 375994 0
Part 1 Blood: Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12 hours after morning dose.
Days 2-4
Part 2: Day 1: pre-dose, 0.5, 1, 2, 4, 6, 9, 9.5, 10, 11, 13, 15 and 18 hours after morning dose.
Days 2-9: one sample within 30 min prior to the morning and evening dosing, respectively every day
Days 10-13: pre-dose, 0.5, 1, 2, 4, 6, 9, 9.5, 10, 11, 13, 15, 18, 24, 36, 48, 60 and 72 hours after morning dose on Day 10.

Eligibility
Key inclusion criteria
1. Are capable of signing informed consent form (ICF) and complying with study procedures;
2. Women of childbearing potential (WOCBP) must have a negative pregnancy test and be practicing a medically acceptable method of contraception. All male patients with female partners of child-bearing potential must use two acceptable methods of contraception, during and for 3 months after participation in the study.
3. Nonsmoker, defined as not having smoked more than 2 cigarettes a day during the 6 months before screening. During the study, subject should be able to limit the use of tobacco products to 2 cigarettes a day;
4. Able to abstain from the consumption of alcohol and any alcohol-containing products from 48 hours before dosing through the end of the study;
5. Able to limit the consumption of coffee and any caffeine-containing products to four cups a day during the study;
6. Body mass index (BMI) of 18 to 32 kg/m2 inclusive and body weight not less than 50 kg;
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity
2. Clinically significant findings of screening clinical safety laboratory tests
3. Subjects with a mean systolic blood pressure of three measurements >150 mmHg, or a mean diastolic blood pressure of three measurements >90 mmHg at screening. Blood pressure will be measured at sitting position
4. Known or suspected malignancy, except adequately treated basal cell carcinoma
5. Positive blood screen for human immunodeficiency virus (HIV), or hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
6. A history of seizure. However, a history of febrile seizure is allowed
7. A hospital admission or major surgery within 60 days prior to screening
8. Participation in any other investigational drug trial within 30 days prior to screening
9. DSM-V substance use disorders within 6 months prior to screening
10. A positive result for alcohol or drugs of abuse at screening or admission.
11. Donation or blood collection of more than 1 unit (approximate 450 mL) of blood (or blood products) or acute loss of blood during the 30 days prior to screening
12. Use of prescription or over-the-counter (OTC) medications, and herbal medicines within 30 days prior to dosing
13. A history of suicide attempt in the past 12 months and/or seen by the investigator as having a significant history of risk of suicide or homicide

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)
All eligible subjects will be randomised using a manual randomisation scheme (central randomisation - computer), developed prior to the initiation of the study. This is separate from the enrolment process. The unblinded site Pharmacist will dispense either SIR1-365 or placebo for the subject as per the randomisation schedule. The dispensed IP label will include the subject's name, randomisation number and will state 'SIR1-365 or matching placebo' and the dose. The label will not contain any unblinded information, to disclose whether the content(s) of the bottle are SIR1-365 or placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
NSW

Funding & Sponsors
Funding source category [1] 304069 0
Commercial sector/Industry
Name [1] 304069 0
Sironax Aus Pty Ltd
Address [1] 304069 0
Level 40, 2-26 Park Street, Sydney, NSW 2000
Country [1] 304069 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Sironax Aus Pty Ltd
Address
Level 40, 2-26 Park Street, Sydney, NSW 2000
Country
Australia
Secondary sponsor category [1] 304266 0
None
Name [1] 304266 0
Address [1] 304266 0
Country [1] 304266 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304560 0
Bellberry Ltd
Ethics committee address [1] 304560 0
123 Glen Osmond Road, Eastwood S.A. 5063
Ethics committee country [1] 304560 0
Australia
Date submitted for ethics approval [1] 304560 0
09/10/2019
Approval date [1] 304560 0
13/11/2019
Ethics approval number [1] 304560 0

Summary
Brief summary
This research project is being conducted to look at the safety, tolerability, pharmacokinetics (PK, how the human body processes a substance) and pharmacodynamics (PD, how the human body interacts with a substance) of SIR1-365 when given to healthy volunteers as a single oral dose or as multiple oral doses for up to 10 consecutive days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97386 0
Dr Charlotte Lemech
Address 97386 0
Scientia Clinical Research Ltd
Bright Building, Level 5, Corner of High & Avoca Street, Randwick, Sydney NSW 2031
Country 97386 0
Australia
Phone 97386 0
+61 2 9382 5807
Fax 97386 0
Email 97386 0
Charlotte.lemech@scientiaclinicalresearch.com.au
Contact person for public queries
Name 97387 0
Ms Puja Motwani
Address 97387 0
Scientia Clinical Research Ltd
Bright Building, Level 5, Corner of High & Avoca Street, Randwick, Sydney NSW 2031
Country 97387 0
Australia
Phone 97387 0
+61 2 9382 5820
Fax 97387 0
Email 97387 0
puja.motwani@scientiaclinicalresearch.com.au
Contact person for scientific queries
Name 97388 0
Ms Puja Motwani
Address 97388 0
Scientia Clinical Research Ltd
Bright Building, Level 5, Corner of High & Avoca Street, Randwick, Sydney NSW 2031
Country 97388 0
Australia
Phone 97388 0
+61 2 9382 5820
Fax 97388 0
Email 97388 0
puja.motwani@scientiaclinicalresearch.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Combined de-identified participant data may be made publicly available through peer reviewed journal publications or presentations at professional forums.
What supporting documents are/will be available?
No other documents available
Summary results
No Results