None listed
Conditions
Brief summary
This is a phase 1, single-center, randomized, open-label, 3-way crossover study to evaluate the pharmacokinetics of PBT434 after administration of a tablet formulation in the fed and fasted states and a powder in capsule formulation which has been utilized in previous Phase 1 investigations
Interventions
In Part I, each subject will receive three treatments (Treatments A, B, C) once each in a random sequence during Periods 1, 2, 3, as follows:
Treatment A: Single dose of PBT434 200 mg PIC (1x200 mg capsule) in the fasted state (after a minimum 10-hr fast), followed by a 4-hr fast
Treatment B: Single dose of PBT434 200 mg tablet (2x100 mg tablets) in the fasted state (after a minimum 10-hr fast), followed by a 4-hr fast
Treatment C: Single dose of PBT434 200 mg tablet (2x100 mg tablets) in the fe
In Part I, each subject will receive three treatments (Treatments A, B, C) once each in a random sequence during Periods 1, 2, 3, as follows: Treatment A: Single dose of PBT434 200 mg PIC (1x200 mg capsule) in the fasted state (after a minimum 10-hr fast), followed by a 4-hr fast Treatment B: Single dose of PBT434 200 mg tablet (2x100 mg tablets) in the fasted state (after a minimum 10-hr fast), followed by a 4-hr fast Treatment C: Single dose of PBT434 200 mg tablet (2x100 mg tablets) in the fed state (30 minutes following the start of a high-fat, high-calorie meal), followed by a 4-hr fast In Part II, each subject will receive three treatments (Treatments D, E, F) once each in a random sequence during Periods 1, 2, 3, as follows: Treatment D: Single dose of PBT434 75 mg tablet (1x75 mg tablet) in the fasted state (after a minimum 10-hr fast), followed by a 4-hr fast Treatment E: Single dose of PBT434 75 mg tablet (1x75 mg tablet) in the fed state (30 minutes following the start of a high-fat, high-calorie meal), followed by a 4-hr fast Treatment F: Single dose of PBT434 75 mg tablet (1x75 mg tablet) in the fed state (30 minutes following the start of a low-fat meal), followed by a 4-hr fast In Part III, subjects will receive 75 mg PBT434 twice daily for 8 days.
Sponsors
Alterity Therapeutics Limited
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female between 18 and 65 years old (inclusive) (Parts I and II) or 18-75 years old (Part III) at the time of consent. Note: Part III will include at least 4 subjects =50 years old 2. In good general health, free from clinically significant medical or psychiatric illness based on medical/surgical history, physical examination, 12-lead ECG, and clinical laboratory tests 3. Vital signs within ranges and stable (measured in supine position after 5 minutes rest) 4. Body Mass Index greater than or equal to 18kg/m2 and less than or equal to 30 kg/m2 5. Adequate venous access in the left or right arm to allow collection of the required number of blood samples 6. Provides written informed consent 7. Willing to comply with all study procedures and requirements, including consumption of a standardized high-fat, high calorie meal 8. Women of childbearing potential are using two acceptable methods of contraception through 90 days after the final dose 9. Male subjects must be using an acceptable birth control method through 90 days after the final dose 10. Female subjects must agree to not donate ova for 90 days after the final dose. Male subjects must agree to not donate sperm for 90 days after the final dose 11. No significant changes to diet within the 30 days prior to dosing through study completion 12. Willing and able to abstain from caffeine from 48 hours prior to check-in through 48 hours after dosing in each study period
Exclusion criteria
1. Women who are pregnant or breastfeeding 2. History or presence of malignancy, with the exception of adequately treated localized skin cancer (basal cell or squamous cell carcinoma) or carcinoma in-situ of the cervix, which are allowed 3. Evidence of any clinically relevant medical illness, including cardiovascular, hematological, gastrointestinal, hepatic, renal, rheumatologic, endocrine, pulmonary, neurologic, psychiatric or skin disorders 4. Clinically significant surgical procedure within 3 months prior to screening or anticipated surgery during the study 5. History of epilepsy (other than febrile seizures during childhood) 6. History of head trauma with loss of consciousness, amnesia or skull fracture 7. Currently suffers from clinically significant systemic allergic disease or has a history of significant drug allergies including a history of anaphylactic reaction; allergic reaction due to any drug which led to significant morbidity 8. Unable to swallow study medication 9. History or presence of cardiac arrhythmia or congenital long QT syndrome 10. QTcF >450 msec for men or >470 msec for women on screening or baseline ECG 11. Use of any tobacco or nicotine containing products (including social use) in the 3 months prior to dosing or a positive urine cotinine test prior to dosing 12. Regular alcohol consumption >2 units/day (1 unit = 250 mL of beer, 100 mL of wine, or 30 mL of distilled spirits or liquor) or alcohol consumption within 24 hours prior to dosing until study completion 13. Positive urine drug or alcohol breathalyzer test prior to study entry (during screening or Day -1) or during the study, or history of alcohol or drug abuse in the 12 months prior to dosing 14. Evidence of renal insufficiency, as indicated by an estimated creatinine clearance <90 mL/min using the Cockcroft-Gault equation 15. Any of the following abnormalities in liver enzymes at Screening or Baseline: a. Aspartate transaminase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN) b. Alkaline phosphatase (ALP) or total bilirubin (TBil) >2 times the ULN 16. Hemoglobin value less than the lower limit of normal 17. Positive results of serology screening for hepatitis B (hepatitis B surface antigen [HBsAg]), hepatitis C (anti-hepatitis C virus [HCV] antibodies) or HIV (HIV antibodies type 1 and 2) 18. Any acute illness, clinically significant infection or clinically significant abnormal laboratory result within 28 days prior to dosing 19. Use of any prescription medication within 28 days prior to dosing 20. Use of any non-prescription medication (including non-steroidal anti-inflammatory drugs), herbal remedy (including St. John’s Wort) or vitamin supplement, within 14 days prior to dosing and throughout the study Note: Approved doses of paracetamol (acetaminophen, up to a maximum of 2,000 mg/day) may be permitted during Screening and while on study at the investigator’s discretion. 21. Use of an investigational drug or device within 28 days or 10 half-lives of the drug, whichever is longer, prior to start of dosing (or within 6 months prior to Day -1 if investigational drug was a biologic) 22. Clinically significant blood loss or blood or plasma donation >550 mL within 90 days prior to start of dosing 23. As a result of history and physical examination, the Investigator considers the subject unfit for the study 24. Any condition (e.g., chronic diarrhea, inflammatory bowel disease) or prior surgery (including surgery of the gastrointestinal and/or biliary tract) that could interfere with drug absorption, distribution, metabolism, or excretion of the IP 25. The subject has previously participated in a clinical trial of PBT434 within 28 days prior to dosing or experienced a clinically significant adverse event in a previous clinical trial of PBT434 Note: Subjects who have previously participated in a clinical trial of PBT434 may be enrolled only if approved by the Medical Monitor
Outcome results
None listed