None listed
Conditions
Brief summary
Groups of healthy male subjects will be administered escalating single doses of PXS-5338K to examine the safety, pharmacokinetic and pharmacodynamic profiles of PXS-5338K. This study will also investigate the safety, pharmacokinetic and pharmacodynamic profiles after repeated doses of PXS-5338K over a 14 day period.
Interventions
PXS-5338K has been developed to be an anti-fibrotic medication for once daily oral administration in patients for the treatment of NASH (non-alcoholic steatohepatitis) and other fibrosis based diseases.
Subjects will be randomised to receive PXS-5338K (active) or matching placebo in single ascending doses (SAD) or multiple ascending doses (MAD).
PXS-5388K will be in a capsule form and will be administered orally followed by 200ml of water.
Dose levels for SAD will begin at 10 mg and increase
PXS-5338K has been developed to be an anti-fibrotic medication for once daily oral administration in patients for the treatment of NASH (non-alcoholic steatohepatitis) and other fibrosis based diseases. Subjects will be randomised to receive PXS-5338K (active) or matching placebo in single ascending doses (SAD) or multiple ascending doses (MAD). PXS-5388K will be in a capsule form and will be administered orally followed by 200ml of water. Dose levels for SAD will begin at 10 mg and increase to 400 mg over 6 Cohorts. Dose for each cohort are as follows: Cohort 1 – PXS-5338K = 10 mg Cohort 2 – PXS-5338K = 30 mg Cohort 3 – PXS-5338K = 60 mg Cohort 4 – PXS-5338K = 100 mg Cohort 5 – PXS-5338K = 200 mg Cohort 6 – PXS-5338K = 400 mg The doses for the MAD phase will be chosen based on the safety/tolerability data collected from the SAD phase. Cohort 7, Cohort 8 and Cohort 9 of MAD study will be planned following consideration of safety, tolerability and PK assessment of preceding SAD and/or repeat dose cohorts. However the most likely doses for MAD study will be between 60 and 200 mg for 14 days once daily. For the SAD, there will be outpatient visits on Day 3 and 4. For the MAD Phase, follow up visits will be done on Day, 16, 17 and 18. The Exit Evaluation visit will be done at Day 5 for the SAD and Day 21 for the MAD.
Sponsors
Pharmaxis Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
Male
Age
18 Years to 60 Years
Healthy volunteers
Yes
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; QTcF (QTc Fredericia’s correction) less than or equal to 450 ms, PR interval of 120-210 ms and a QRS duration less than or equal to 120 ms. 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 one other method of contraception, from Screening and 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 six months prior to dosing). 6. Have given written informed consent to participate in this study in accordance with local regulations.
Exclusion criteria
1. Clinically significant abnormal findings on the physical examination or medical history which, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results. 2. Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, skin or cardiovascular disease or any other condition, which, 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. Evidence of abnormal wound healing (e.g. hypertrophic scars) as the result of surgery or trauma as deemed by the Principal Investigator or delegate. 5. Presence of a currently healing wound, recent musculoskeletal injury or currently healing fracture 6. 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, whichever is greater, or use of any over-the-counter, complementary or alternative medicine 48 hours prior to the start of dosing (excluding paracetamol). 7. At investigator discretion if Systolic blood pressure <100 or >160 mmHg, diastolic blood pressure <50 or >95 mmHg and heart rate (HR) <45 or >100 bpm. 8. ALT, AST or bilirubin >1.5x ULN. 9. Hb, WBC, neutrophils, platelets < LLN 10. Evidence of significant renal insufficiency, as indicated by an estimated creatinine clearance using the Cockcroft-Gault formula of less than 60 mL/min at Screening. 11. Positive Screening test for Hepatitis B surface antigen or Hepatitis C antibody or HIV (human immunodeficiency virus). 12. History of drug abuse in the last 2 years. 13. Males who regularly drink more than three (3) units of alcohol daily (1 unit = 285 mL beer (4.9% Alc./Vol), 100 mL wine (12% Alc./Vol), 30mL spirit (40% Alc./Vol)). 14. Used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks before screening and 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 at least 48 hours prior to admission to the clinical facility, and whilst confined to the clinical facility. 16. 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 and during the conduct of the study. 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 Principal Investigator. 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. Any condition that would interfere with drug absorption (e.g. chronic diarrhoea). 20. Have participated in a clinical trial or have received an experimental therapy within 30 days or 10 half-lives of the drug, whichever is the longer, prior to dosing. 21. Clinically significant abnormality detected on telemetry pre-dose. 22. Systemic infection other than common cold in the week prior to dosing. 23. Have received any vaccines (e.g. influenza) within 30 days before the first dose administration and during the conduct of the study.
Outcome results
None listed