A Randomized, Placebo-Controlled, Double-Blinded, First-in-Human, Adaptive Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses (Part A) and Multiple Ascending Doses (Part B) of Orally Administered ATH-1020 in Healthy Young and Elderly Subjects
Overview
- Phase
- Phase 1
- Intervention
- ATH-1020
- Conditions
- Healthy Volunteers
- Sponsor
- Athira Pharma
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of ATH-1020 in healthy young and elderly subjects.
Detailed Description
This is a Phase 1 first-in-human, 2-part adaptive study. Both Part A and Part B will be performed in a randomized, placebo-controlled, and double-blind manner. Part A - Single Ascending Dose (SAD) Part A will be a SAD study investigating multiple dose levels of ATH 1020. Part B - Multiple Ascending Dose (MAD) Part B will be a multiple ascending dose (MAD) study investigating multiple dose levels of ATH-1020. Subjects in Cohort B5 (4 subjects) will additionally undergo CSF sampling pre-dose on Day 4 and up to 3 post dose timepoints to evaluate ATH-1020 blood-brain-barrier penetration
Investigators
Eligibility Criteria
Inclusion Criteria
- •All Subjects
- •Body mass index (BMI) of ≥ 18.0 and ≤ 32.0 kg/m2 at Screening, with minimum weight of 60 kg.
- •Subjects in generally good health per the investigator's discretion.
- •Male subjects and their partners must be willing to comply with the contraceptive requirements of the study.
- •Subjects must have adequate venous access.
- •Part A (SAD)
- •Male subjects aged 18 to 50 years at the time of signing the informed consent.
- •Part B (MAD)
- •Male subjects aged 18 to 50 years (Cohorts B1, B2, B3, and B5); male and post-menopausal female subjects aged 65 to 85 years (Cohort B4) at the time of signing the informed consent.
Exclusion Criteria
- •History of significant drug allergies (including to any excipients) or of anaphylactic reaction.
- •Any condition per the investigator's discretion, which while not requiring chronic medication use, is likely to require intermittent/acute therapeutic intervention.
- •Any history of seizures or loss of consciousness for an unknown reason.
- •History of or positive results of serology screening for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
- •Abnormal liver tests
- •Impaired renal function.
- •History of having taken another investigational drug within 30 days prior to Admission (Day -1).
- •Major surgery within 90 days prior to Admission (Day -1) or anticipated surgery during the study.
- •Part A (SAD)
- •Female subjects are not permitted.
Arms & Interventions
ATH-1020
ATH-1020 in oral form. Participants in the single ascending dose cohort (Cohort A) will receive a single dose of ATH-1020. Participants in the multiple ascending dose cohort (Cohort B) will receive up to nine doses of ATH-1020 (up to 4 for cohort B5).
Intervention: ATH-1020
Placebo
Placebo in oral form. Participants in the single ascending dose cohort (Cohort A) will receive a single dose of Placebo. Participants in the multiple ascending dose cohort (Cohort B) will receive up to nine doses of placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time Frame: Up to 12 days post initial dosing (Part A); Up to 19 days post initial dosing (Part B)
Safety and tolerability of single or multiple ascending doses of ATH-1020 as measured by vital signs and clinical laboratory measurements.
Secondary Outcomes
- Time to maximum observed plasma concentration (Tmax)(Samples collected pre-dose and at predetermined timepoints within 48 hours post-dose.)
- Plasma concentration at the end of the dosing interval (Ctrough)(Samples collected pre-dose and at predetermined timepoints within 24 hours post-dose.)
- Area under the plasma concentration time curve (AUC)(Samples collected pre-dose and at predetermined timepoints within 48 hours post-dose.)
- Half-life (t1/2)(Samples collected pre-dose and at predetermined timepoints within 48 hours post-dose.)
- Amount of IMP excreted unchanged in the urine (Ae)(Samples collected pre-dose on Day 1 and predetermined timepoints on Day 1, 9, and 10, within 24 hours post-dose.)
- Maximum observed plasma concentration (Cmax)(Cmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.)