None listed
Conditions
Brief summary
The primary purpose of the study is to determine the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PXS-5382A after oral administration SAD This is a randomised, double-blind, placebo controlled, dose escalating study with single ascending dose of PXS-5382A. There will be 6 cohorts consisting of 8 subjects each. Subjects within a cohort will be randomly assigned to one of the two groups (PXS-5382A or placebo) in a 3:1 ratio respectively. Sentinel dosing will be conducted for each cohort, such that; Sentinel dosing – Total N = 2, where N=1 = PXS-5382A N=1 = Placebo Main Cohort – Total N = 6, where N=5 = PXS-5382A N=1 = Placebo Doses will be escalated across the cohorts but not within each cohort. The starting dose and incremental dose increase through the cohorts has been determined based on the results of the pre-clinical studies. MAD Multiple ascending doses of PXS-5382A will be assessed during the MAD phase of the study. Within each cohort, each subject will be randomly assigned to one of the two groups (PXS-5382A or placebo) in a 3:1 ratio respectively wherein each subject will receive the active drug or placebo once daily. The doses and dosing duration chosen for MAD will be based on evaluation of the PK data and all safety information as well as any other relevant data that is available from the SAD phase
Interventions
This is a randomised, double-blind, placebo controlled, dose escalating Phase 1 study. The study will follow a sequential dose-escalating design and will have two phases; the Single Ascending Dose phase and the Multiple Ascending Dose phase.
Sentinel dosing will be conducted for each cohort, such that;
Sentinel dosing – Total N = 2, where
N=1 = PXS-5382A
N=1 = Placebo
Main Cohort – Total N = 6, where
N=5 = PXS-5382A
N=1 = Placebo
SAD Phase
Cohort 1 PXS-5382A = 5mg
Cohort 2 PXS-5382A= 10 mg
Co
This is a randomised, double-blind, placebo controlled, dose escalating Phase 1 study. The study will follow a sequential dose-escalating design and will have two phases; the Single Ascending Dose phase and the Multiple Ascending Dose phase. Sentinel dosing will be conducted for each cohort, such that; Sentinel dosing – Total N = 2, where N=1 = PXS-5382A N=1 = Placebo Main Cohort – Total N = 6, where N=5 = PXS-5382A N=1 = Placebo SAD Phase Cohort 1 PXS-5382A = 5mg Cohort 2 PXS-5382A= 10 mg Cohort 3 PXS-5382A= 20 mg Cohort 4 PXS-5382A= 50 mg Cohort 5 PXS-5382A= 100 mg Cohort 6 PXS-5382A=200 mg MAD Phase The exact number of cohorts in the MAD phase of the study will be determined after review of the SAD phase data. It is likely that there will be 3 cohorts consisting of 8 subjects each per cohort in the MAD phase of the study. The selection of appropriate doses, dosing duration and study population for the MAD phase will be confirmed upon evaluation of the PK data and all safety information as well as any other relevant data that is available from the SAD phase. Possible dose range for MAD is between 60 and 200 mg. The mode of administration will be oral tablet. The anticipated duration is 7-14 days. For each subject, the duration of the study clinic visits from screening (allowing 28 days) to the Day 14 (± 2) Follow-Up Visit is approximately 6 weeks. For each subject in SAD, clinical facility confinement will be approximately 4 days, starting on Day -1, with discharge following the 72 hour post-dose assessments on the morning of Day 4. Subjects will return for out-patient visits on Days 5 and 14. MAD: The duration of dosing for the MAD phase will be determined post review of the SAD phase data, however this will be no longer than 14 days but could be shorter for example 5 half-lives of PXS-5382A. Subjects will remain in the unit for the entire duration of the MAD dosing and will comply with follow-up visits as planned.
Sponsors
Pharmaxis
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy males, aged between 18 and 60 years (inclusive). 2. Eligibility of the subjects will be 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 (Fredericia’s corrected QT) > or equals to 450 ms, PR interval of 120-210 ms and a QRS duration < or equals to 120 ms. 5. Adequate venous access in the left or right arm to allow collection of a number of blood samples. 6. Male subjects with female partners of childbearing potential may be enrolled if they: a. are documented to be surgically sterile (vasectomy at least six months prior to dosing), or b. practice true abstinence for 30 days after the study drug administration, or c. 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 use an intra uterine device (IUD). 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.
Exclusion criteria
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, 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 impact the validity of the study results. 3. History of significant drug allergies or significant allergic reaction or currently suffers 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 is anticipated to receive any prescription systemic or topical medication, or any over the counter, complimentary 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 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 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)). 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 defined periods (e.g., for at least 48 hours prior to admission to the clinical facility, and whilst confined to the clinical facility). 16. Consumption of: a. Grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges (CYP450 enzymes) within 7 days prior to administration of the study drug. b. Poppy seeds and poppy seed products within 7 days prior to administration of the study drug. c. Alcohol within 48 hours 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 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. 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 3 months or 5 half-lives of the drug, whichever is the longer, prior to dosing. 21. Clinically significant abnormality detected on cardiac telemetry pre-dose. 22. Systemic infection other than coryza in the last 4 weeks prior to dosing.
Outcome results
None listed