Atypical Parkinsonism Nervous System Diseases
Conditions
Interventions
Volunteers receive the following oral regimens across Days 1 to 8 of the study:
- Regimen A: ATH434 Tablet, 75 mg twice daily (BID) on Day 1 to Day 7, in the fed state
- Regimen B: [14C]-ATH434 Oral C
Sponsors
Alterity Therapeutics Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Must provide written informed consent 2. Must be willing and able to eat the standard breakfasts and evening meals provided on Days 1 to 8 3. Must be willing and able to communicate and participate in the whole study 4. Age 30 to 65 years inclusive at the time of signing informed consent 5. Must agree to adhere to the contraception requirements 6. Healthy males 7. Body mass index (BMI) of 18.0 to 32.0 kg/m2 as measured at screening 8. Must have regular bowel movements (i.e. average stool production of =1 and =3 stools per day)
Exclusion criteria
Exclusion criteria: 1. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients 2. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active 3. History or evidence of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator 4. History of seizures, including history of febrile seizures during childhood 5. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 6. Evidence of current SARS-CoV-2 infection within 4 weeks of first IMP administration or not fully recovered from COVID-19 symptoms by the screening visit 7. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert’s Syndrome are not allowed 8. Haemoglobin below the lower limit of the laboratory reference range at screening 9. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results 10. Evidence of renal impairment at screening, as indicated by an estimated glomerular filtration rate (eGFR) of 21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) 19. A confirmed positive alcohol breath test at screening or admission 20. Current smokers and those who have smoked within the last 12 months. A confirmed positive urine cotinine test at screening or admission 21. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months 22. Confirmed positive drugs of abuse test result at screening or admission 23. Subject answers "yes" to "Suicidal Ideation" Items 1 or 2 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening 24. Subjects who are, or are immediate family members of, a study site or sponsor employee 25. Failure to satisfy the investigator o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Mass balance recovery of total radioactivity in all excreta (urine and faeces): CumAe and Cum%Ae collected from Day 7 of the study until discharge. 2. Collection of whole blood, plasma, urine and faeces samples for analysis of total radioactivity collected from Day 7 of the study until up to discharge. 3. PK parameters for ATH434, metabolites and total radioactivity: Tlag, Tmax, Cmax, AUC(0-last), AUC(0-inf), AUC(0-tau), T1/2 and metabolite ratios, where applicable, in plasma samples collected throughout the study until Day 15. 4. Collection of plasma, urine and faeces samples for metabolite profiling, structural identification, and quantification analysis, collected throughout the study until up to discharge. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Determination of rate and routes of elimination of total radioactivity by Ae, %Ae, CumAe and %CumAe, by collection interval using urine and faeces samples collected throughout the study until up to discharge. 2. Identification of the chemical structure of each metabolite accounting for more than 10% by AUC of circulating total radioactivity or accounting for 10% or more of the dose in excreta in plasma, urine and faeces samples collected throughout the study until up to discharge. 3. Evaluation of whole blood:plasma concentration ratios for total radioactivity in plasma samples collected from Day 8 until Day 15. 4. To provide additional safety and tolerability information for ATH434 by assessing: incidence of adverse events (AEs), physical examinations and change from baseline for vital signs, electrocardiograms (ECGs), and laboratory safety tests from admission until discharge. | — |
Countries
England, United Kingdom
Contacts
Public ContactCynthia Wong
Outcome results
None listed