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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04183517




Registration number
NCT04183517
Ethics application status
Date submitted
26/11/2019
Date registered
3/12/2019
Date last updated
25/06/2020

Titles & IDs
Public title
A Two-part Pharmacokinetic Study of PXS-5382A in Healthy Adult Males
Scientific title
A Two-part Pharmacokinetic Study of PXS-5382A in Healthy Adult Males
Secondary ID [1] 0 0
PXS-5382A-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pharmacokinetics 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PXS-5382A

Experimental: Fasted - PXS-5382A administered as a single dose in the fasted state

Experimental: Fed - PXS-5382A administered as a single dose in the fed state

Experimental: Twice daily - PXS-5382A administered twice daily for 5 days in the fed state


Treatment: Drugs: PXS-5382A
Orally once daily or twice daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cmax after oral administration of PXS-5382A - Maximum plasma concentration
Timepoint [1] 0 0
6 days
Primary outcome [2] 0 0
Tmax after oral administration of PXS-5382A - Time of the observed maximum plasma concentration
Timepoint [2] 0 0
6 days
Primary outcome [3] 0 0
AUC0-inf of PXS-5382A - Area under the plasma concentration-time curve (AUC) from time zero extrapolated to infinity
Timepoint [3] 0 0
6 days
Primary outcome [4] 0 0
t1/2 of PXS-5382A - Terminal plasma elimination half-life
Timepoint [4] 0 0
6 days
Secondary outcome [1] 0 0
Maximum percentage inhibition plasma LOXL2 of PXS-5382A - Maximum measured plasma LOXL2 target engagement following PXS-5382A administration
Timepoint [1] 0 0
6 days
Secondary outcome [2] 0 0
Incidence and severity of Adverse Events - A treatment-emergent adverse events (TEAE) will be summarized by treatment and overall, and summarized for each treatment by severity and relationship to study drug. All TEAEs leading to withdrawal, or SAEs, will be summarized.
Timepoint [2] 0 0
6 days
Secondary outcome [3] 0 0
Number of subjects with clinical laboratory test abnormalities - The clinical laboratory will include hematology (hematocrit, hemoglobin, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, platelet count, red blood cell count, white blood cell count), clinical chemistry (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, calcium, chloride, cholesterol, creatinine, creatine phosphokinase, direct bilirubin, estimated glomerular filtration rate, gamma glutamyl transferase, glucose. inorganic phosphate, iron, lactate dehydrogenase, phosphorus, potassium, sodium, total bilirubin, total CO2, total protein, triglyceride, urea, uric acid), and urinalysis (bilirubin, blood, color and appearance, glucose, ketones, leukocyte esterase, nitrite, pH, protein, specific gravity, urobilinogen, microscopic examination, electrolytes). Abnormality will be determined by the investigator.
Timepoint [3] 0 0
6 days
Secondary outcome [4] 0 0
Number of subjects with vital signs abnormalities - The vital sign will include blood pressure (mmHg), pulse rate (bpm), respiratory rate (breaths/min), and body temperature (degree Celsius). Abnormality will be determined by the investigator.
Timepoint [4] 0 0
6 days

Eligibility
Key inclusion criteria
1. Healthy males, aged between 18 and 60 years (inclusive).

2. Eligibility of the subjects based on clinical history, physical examination, ECG and
Lab results

3. BMI between 18.5 kg/m2 and 30.0 kg/m2 inclusive.

4. No clinically relevant abnormality in an ECG; QTcF (Fridericia's corrected QT) = 450
ms, PR interval of 120-210 ms and a QRS duration = 120 ms.

5. Adequate venous access in the left or right arm to allow dosing and collection of a
number of blood samples.

6. Male subjects with female partners of childbearing potential may be enrolled if they:

1. are documented to be surgically sterile (vasectomy at least six months prior to
dosing), or

2. practice true abstinence for 30 days after the study drug administration, or

3. agree to use a barrier method of contraception (e.g. condom) from Screening and
until 30 days after administration of the study. Additionally, the female partner
must use a highly effective hormonal method, such as birth control pills,
patches, implants or injections; or used an intra uterine device (IUD).

4. Contraceptive requirements do not apply to subjects who are exclusively in
same-sex relationships.

7. 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, medical history,
ECG or laboratory results as deemed by the PI (or delegate).

2. Clinically significant gastrointestinal, renal, hepatic, neurologic, haematologic
(including thalassaemia), endocrine, oncologic, pulmonary, immunologic, psychiatric,
skin or cardiovascular disease or any other condition, which, in the opinion of the PI
(or delegate), would jeopardise the safety of the subject or impacted the validity of
the study results.

3. History of significant drug allergies or significant allergic reaction or suffer from
clinically significant systemic allergic disease. Mild hay fever is acceptable.

4. Evidence of abnormal wound healing (e.g. hypertrophic scars) as the result of surgery
or trauma as deemed by the PI or delegate.

5. Have received or are anticipated to receive any prescription systemic or topical
medication, or any over the counter, supplements, complementary or alternative
medicine 7 days prior to the start of dosing or within 5 half-lives of the drug
whichever is longer (excluding paracetamol).

6. Systolic BP < 90 or > 140 mmHg, diastolic BP < 40 or > 90 mmHg and HR < 40 or > 100
beats per minute (BPM).

7. ALT, AST or total bilirubin > 1.5x ULN.

8. Gilbert's syndrome sufferers are not eligible.

9. Evidence of significant renal insufficiency, as indicated by an estimated creatinine
clearance using the Cockcroft-Gault formula of less than 80 mL/min at Screening.

10. Positive Screening test for Hepatitis B surface antigen or Hepatitis C antibody or
human immunodeficiency virus (HIV)

11. Any condition directly or indirectly caused by or associated with Transmissible
Spongiform Encephalopathy (TSE) Creutzfeldt-Jakob Disease (CJD) variant
Creutzfeldt-Jakob Disease (vCJD) or new variant Creutzfeldt-Jakob Disease (nvCJD)

12. History of drug abuse in the last 2 years.

13. Males who regularly drink more than four (4) units of alcohol daily (1 unit = 285 mL
beer (4.9% Alc./Vol), 100 mL wine (12% Alc./Vol), 30 mL spirit (40% Alc./Vol)).

14. Use nicotine-containing products (e.g., cigarettes, e-cigarettes, cigars, chewing
tobacco, snuff) within 6 weeks before screening and were unable to abstain from using
these products until study completion.

15. Unable to abstain from consuming caffeine and/or xanthine products (i.e., coffee, tea,
chocolate, and caffeine-containing sodas, colas, etc.) for defined periods (eg, to the
clinical facility).

16. Consumption of:

1. Grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges
(CYP450 enzymes) within 7 days prior to administration of the study drug up to
Exit Evaluation visit.

2. Poppy seeds and poppy seed products within 7 days prior to administration of the
study drug up to Exit Evaluation visit.

3. Alcohol within 48 hours prior to administration of study drug up to Exit
Evaluation visit.

17. Positive urine screen for drugs of abuse and alcohol breath test at screening and
study check-in. Subjects may undergo a repeat urine drug screen or alcohol breath test
at the discretion of the PI (or delegate).

18. 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.

19. Have dietary restrictions that preclude the consumption of the required high-fat meal
in Part A.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
Recruitment hospital [1] 0 0
CMAX - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pharmaxis
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase I, open-label, two-part in healthy adult males. There will be up to 12
subjects with 6 subjects in each part of the study. Subjects from Part A are eligible to
participate in Part B.

For Part A, each of the 6 subjects will complete two periods of the study with washout period
of 7 days between. Each subject during participation in the study will receive a dose of PXS
5382A orally in a fed state and a fasted state.

For Part B, repeated oral BID administration of PXS-5382A will be performed in the Fed state
and dose will be dependent on analysis of Part A.

In both part A and B PK, PD and safety assessments will be collected.
Trial website
https://clinicaltrials.gov/show/NCT04183517
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Angela Molga, MBBS
Address 0 0
CMAX Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications