The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000332123
Ethics application status
Approved
Date submitted
20/02/2019
Date registered
4/03/2019
Date last updated
22/04/2020
Date data sharing statement initially provided
4/03/2019
Date results information initially provided
22/04/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Single Ascending Dose and Multiple Ascending Dose Phase 1 Study of PXS-5505A Administered Orally in Healthy Adult Males
Scientific title
A Single Ascending Dose and Multiple Ascending Dose Phase 1 Study to evaluate safety tolerability, pharmacokinetics (PK), and pharmacodynamics of PXS-5505A Administered Orally in Healthy Adult Males
Secondary ID [1] 297451 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Organ Fibrosis 311636 0
Condition category
Condition code
Inflammatory and Immune System 310258 310258 0 0
Connective tissue diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in two parts. Part A single ascending dose (SAD) with total 5 Cohorts and Part B Multiple ascending dose (MAD).
Oral doses of PXS-5505A capsules (10 mg, 50 mg, 100 mg, 200 mg, and 300 mg) will be administered to subjects in SAD cohorts.
Oral doses of PXS-5505A capsules (100 mg and 200mg) are planned to be administered to subjects in MAD Cohorts based on available safety, PK and PD data from the SAD Cohorts. The ascending doses used for MAD Cohorts are planned for 100 and 200 mg based on the availability of safety, PK and PD data from SAD Cohorts.
MAD Cohorts will start once all the SAD Cohorts are completed and evaluated with safety and PK/PD data
Intervention code [1] 313706 0
Treatment: Drugs
Comparator / control treatment
Placebo will be the same capsule type used for the IP filled with the same excipients (mannitol and Mg-stearate).
Control group
Placebo

Outcomes
Primary outcome [1] 319146 0
The primary endpoints of the study are to evaluate safety and tolerability of single ascending or repeated doses of PXS-5505A by measuring Adverse Events, Change in ECGs, Blood pressure, Heart Rate and Laboratory Assessments.

Safety and tolerability of PXS-5505A will be assessed by observation of the incidence, severity, causality and seriousness of adverse events ; vital signs (blood pressure, heart rate, respiratory rate, and oral temperature); laboratory tests (drug and alcohol screening, hematology and coagulation, and biochemistry); and medical surveillance by clinical site staff. Possible and know AE may be liver inflammation and increased blood pressure.
Timepoint [1] 319146 0

Vital signs to be assessed at Screening, Check-in and on Day 1 at pre-dose within 30 minutes and at 15 and 30 minutes and 1, 2, 4, 6, 8 and 12 hours, and on Day 2, Day 3, Day 4, and Day 5 at 24, 48, 72, and 96 hours post-dose respectively
ECGs at Screening and on Day 1 at pre-dose within 30 minutes and at 1, 2, and 4 hours, and on Day 2, Day 3, and Day 5 at 24, 48, and 96 hours post-dose respectively.
Adverse Events will be monitored throughout the study.
Secondary outcome [1] 367123 0
The Secondary outcome of this study is evaluating plasma PK parameters after single and multiple dosing of PXS-5505A

Assessment of plasma pharmacokinetic parameters will be evaluated as below for SAD and MAD

AUC
Cmax
Tmax
T 1/2
Accumulation ratio (for MAD only)
Timepoint [1] 367123 0
Blood samples for plasma PK analysis for MAD part will be taken on Day 1, Day 7 and Day 14 at pre-dose within 30 minutes and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose, on Day 2, Day 8 and Day 15 at 23.5 hours post dose and 38 and 72 hours post dose on Day 14 (Day 16 and 17 respectively). Voided urine for Part B (MAD) will be collected for up to 24 hours after Day 14.
Secondary outcome [2] 367126 0
The Secondary outcome of this study is evaluating serum PD parameters after single and multiple dosing of PXS-5505A

Below parameters will be evaluated for PD profile

Lysyl oxidase like 2 (LOXL2) and other LOX family enzymes where available, activity
in plasma using enzymatic assay
LOXL2, and other LOX family enzymes where available, concentration in plasma
using ELISA method
Timepoint [2] 367126 0
Blood samples for serum PD analysis for MAD part will be taken on Day 1, Day 7 and Day 14 at pre-dose (within 30 minutes before dose) and at 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 2, Day 8 and Day 15 at 23.5 hours post dose and 48 and 72 hours post dose 14th dose (Day 16 and 17 respectively).
Secondary outcome [3] 367127 0
The Secondary outcome of this study is evaluating PD parameters via skin biopsy after single and multiple dosing of PXS-5505A

Below parameter will be assessed to evaluate PD parameter via skin biopsy.

LOX activity in skin
Timepoint [3] 367127 0
Skin biopsies for PD analysis for MAD part will be taken on Day -1 , 4 hours post Day 14 and 72 hours post Day 7 dosing (Day 14).

Eligibility
Key inclusion criteria
1. Male and aged between 18 and 60 years (inclusive).
2. Body Mass Index (BMI) between 18.5 kg/m2 and 30 kg/m2 (inclusive).
3. No clinically relevant abnormality in an ECG
4. Adequate venous access in the left or right arm to allow collection of a number of blood samples.
5. Agrees to use a condom, and in the case of partner who is potentially childbearing at least 1 other method of contraception, from Screening until 30 days after administration of the study drug. Agreed methods of contraception may include approved birth control pills, patches, implants or injections by the subject’s partner, use of an IUD (intra uterine device) by the subject’s partner and/or surgical sterilisation of the participant (vasectomy at least 6 months prior to dosing).
6. Have given written informed consent to participate in this study in accordance with local regulations.
Minimum age
18 Years
Maximum age
60 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Clinically significant abnormal findings on the physical examination or medical history
2. Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, skin or cardiovascular disease or any other condition, that, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
3. History of immediate hypersensitivity to any medication or currently suffers from clinically significant systemic allergic disease.
4. Presence of a currently healing wound, recent musculoskeletal injury or currently healing fracture.
5. Have received or is anticipated to receive any prescription systemic or topical medication within 14 days prior to the start of dosing or within 5 half-lives of the drug, or use of any over-the-counter, complementary or alternative medicine 48 hours prior to the start of dosing
6. At Investigator discretion if systolic blood pressure less than 100 or greater than 160 mmHg, diastolic blood pressure less than 50 or greater than 95 mmHg and heart rate (HR) less than 45 or greater than 100 beats per minute.
7. Alanine aminotransferase (ALT), aspartate transaminase (AST), or bilirubin greater than 1.5x upper limit of normal (ULN).
8. Haemoglobin (Hb), white blood cells (WBC), neutrophils, platelets less than LLN.
9. Evidence of significant renal insufficiency
10. Positive screening test for Hepatitis B surface antigen or Hepatitis C antibody or human immunodeficiency virus (HIV).
11. History of drug abuse in the last 2 years.
12.Males who regularly drink more than 3 units of alcohol daily
15. Used nicotine-containing products
14.Unable to abstain from consuming caffeine and/or xanthine products
15. Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, apple juice, red wine or other alcohol within 7 days prior to administration of study drug until 24 hours after the last dose is administered to the subject.
16. Positive urine screen for drugs of abuse and alcohol breath test
17. Receipt of blood or blood products, or loss or donation of 450 mL or more of blood within 90 days before the first dose administration.
18. Any condition that would interfere with drug absorption
19. Have participated in a clinical trial or have received an experimental therapy within 30 days or 5 half-lives of the drug,
21. Systemic infection other than common cold in the week prior to dosing.
22. Have received any vaccines within 30 days before the first dose administration and during the conduct of the study.
23. Consumption of foods containing appreciable amounts of collagen, including meats, meat products, gravy, confectionary and ice-cream containing gelatin,

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 computer generated randomization schedule generated through the statistical analysis system software will be prepared by the assigned biostatistician and Investigational product will be prepared and dispensed in accordance with the randomization schedule.
Methods used to generate the sequence in which subjects will be randomised (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
Parallel
Other design features
N/A
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

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 hospital [1] 13204 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 25760 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 302023 0
Commercial sector/Industry
Name [1] 302023 0
Pharmaxis Ltd
Address [1] 302023 0
Locked Bag 5015 FRENCHS FOREST NSW 2086
Country [1] 302023 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Pharmaxis Ltd
Address
Locked Bag 5015 FRENCHS FOREST NSW 2086
Country
Australia
Secondary sponsor category [1] 301817 0
None
Name [1] 301817 0
Address [1] 301817 0
Country [1] 301817 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302700 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 302700 0
123 Glen Osmond Road, Eastwood, SA, 5063
Ethics committee country [1] 302700 0
Australia
Date submitted for ethics approval [1] 302700 0
21/11/2018
Approval date [1] 302700 0
11/02/2019
Ethics approval number [1] 302700 0

Summary
Brief summary
This Phase 1, randomised, placebo-controlled, double-blind study will evaluate the safety, tolerability, PK, and PD of PXS-5505A in a single ascending dose (SAD) and multiple ascending dose (MAD) fashion in healthy male volunteers. The study will be conducted in 2 parts: Part A (SAD) and Part B (MAD). The MAD portion of the study will commence after all cohorts of the SAD portion of the study have been completed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91102 0
Prof Jessica Gehlert
Address 91102 0
CMAX Clinical Research Pty Ltd
Level 5, 18a North Terrace
Adelaide
South Australia
Australia
5000
Country 91102 0
Australia
Phone 91102 0
+61 421311 443
Fax 91102 0
Email 91102 0
Jessica.Gehlert@sa.gov.au
Contact person for public queries
Name 91103 0
Dr Brett Charlton
Address 91103 0
Locked Bag 5015 FRENCHS FOREST NSW 2086
Pharmaxis Ltd. 20 Rodborough Road, Frenchs Forest, Sydney NSW 2086, Australia
Country 91103 0
Australia
Phone 91103 0
+61 414 987 338
Fax 91103 0
Email 91103 0
Brett.Charlton@pharmaxis.com.au
Contact person for scientific queries
Name 91104 0
Dr Brett Charlton
Address 91104 0
Locked Bag 5015 FRENCHS FOREST NSW 2086
Pharmaxis Ltd. 20 Rodborough Road, Frenchs Forest, Sydney NSW 2086, Australia
Country 91104 0
Australia
Phone 91104 0
+61 414 987 338
Fax 91104 0
Email 91104 0
Brett.Charlton@pharmaxis.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
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?
Results – basic reporting
Results – plain English summary