This study will evaluate the safety, tolerability and pharmacokinetics of single and multiple doses of ATH-399A in healthy adults and also evaluate the effect of food on ATH-399A in order to develop mechanism-based and/or disease-modifying treatments for Parkinson Disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
76
Orally administered drug in capsule form.
Orally administered drug in capsule form.
Participants will receive single oral dose of 10 mg of ATH-399A capsule
Syneos Quebec Canada
Québec, Canada
Number of TEAEs
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug.
Time frame: Continuously during study period from baseline to follow-up visit: Part 1a: Day-1 to Day 8, Part 1b: Day-1 to Day 16; and Part 2: Day -1 to Day 19
Participants With at Least 1 TEAE
Participants with at least one AE started or after the time of first study drug administration.
Time frame: Continuously during study period from baseline to follow-up visit: Part 1a: Day-1 to Day 8, Part 1b: Day-1 to Day 16; and Part 2: Day -1 to Day 19
Serious TEAEs
An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the criteria listed: Resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other situations.
Time frame: Continuously during study period from baseline to follow-up visit: Part 1a: Day-1 to Day 8, Part 1b: Day-1 to Day 16; and Part 2: Day -1 to Day 19
Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS)
Number of participant whose answers indicate suicidal ideation and/or behavior at follow-up.
Time frame: Part 1a, 1b: Screening, Day -1, Follow-up (1a - Day 16; 1b - Day 19); Part 2: Screening, Day -1, Day 13 (Discharge or early termination)
QTcF Analysis
Participants with abnormal QTcF on ECG (pooled data from the whole study duration)
Time frame: From baseline to follow up visit: Part 1a: Day-1 to Day 8, Part 1b: Day-1 to Day 16; and Part 2: Day -1 to Day 19
Changes in Diastolic Blood Pressure
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Participants will receive single oral dose of 5mg of ATH-399A capsule
Participants will receive single oral dose of 20mg of ATH-399A capsule
Participants will receive single oral dose of 40mg of ATH-399A capsule
Participants will receive single oral dose of 80mg of ATH-399A capsule
Diastolic blood pressure baseline value measured at basline Day 1 pre dose and Day 1 1 hour post dosing
Time frame: Day 1: predose and 1 hour post dosing
Changes in Systolic Blood Pressure
Systolic blood pressure baseline value measured at basline Day 1 pre dose and Day 1 1 hour post dosing
Time frame: Day 1 predose and 1 hour postdosing
Heart Rate Value
Heart rate value measured at Day 1, 1 Hour Post-Dose
Time frame: Day 1, 1 hour post-dose
Temperature Value
Temperature value measured at Day 1, 1 Hour Post-Dose
Time frame: Day 1, 1 Hour Post-Dose
Respiratory Rate Value
Respiratory rate value measured at Day 1, 1 Hour Post-Dose
Time frame: Day 1, 1 Hour Post-Dose
Physical Examination and Neurological Examination Abnormalities Analysis
Participants with abnormal findings on physical and neurological examination (pooled data from the whole study)
Time frame: Part 1a, 1b, 2: Screening, D-1, D3 (Discharge or early termination), Follow-Up: Part 1a: Day 8, Part 1b: Day 16; and Part 2: Day 19
12-Lead Telemetry Abnormalities Analysis
Participants with abnormal findings on 12-lead telemetry (pooled data from the whole study)
Time frame: Part 1a, 1b: D1, D2, D3; Part 2: D1, D2, D12, D13 (Discharge or early termination)
Laboratory Parameter: Creatinine Value
Laboratory parameter: Creatinine level on Day 1
Time frame: Day 1
Laboratory Parameter: Glucose
Laboratory parameter: Glucose level measured on Day 1
Time frame: Day 1
AUC0-t
Plasma Pharmacokinetic (PK) parameter: Area Under the Concentration-Time Curve from Time Zero Until the Last Observed Concentration (AUC0-t) for Part 1a, Part 1b and Part 2. AUC0-t was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 1: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours. Part 2: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours.
AUC0-inf
PK parameter: Area Under The Concentration-Time Curve From Time Zero To Infinity (Extrapolated) (AUC0-inf) for Part 1a, Part 1b and Part 2. AUC0-inf was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 1: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours. Part 2: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours.
Cmax
PK parameter: Maximal Observed Concentration (Cmax) for Part 1a, Part 1b and Part 2. Cmax was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 1: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours. Part 2: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours.
Tmax
PK parameter: Time When The Maximal Concentration Is Observed (Tmax) for Part 1a, Part 1b and Part 2. Tmax was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 1: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours. Part 2: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours.
λz
PK parameter: Individual Estimate Of The Terminal Elimination Rate Constant (λz) for Part 1a, Part 1b and Part 2. λz was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 1: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours. Part 2: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours.
t½ el
PK parameter: Terminal Elimination Half-Life (t½ el) for Part 1a, Part 1b and Part 2. T1/2 el was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 1: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours. Part 2: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours.
Cmax, ss
PK parameter: Maximal Observed Concentration at steady state (Cmax, ss) for Part 2. Cmax,ss was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 2 only: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours.
Cmin ss
PK parameter: Minimal Observed Concentration at steady-state (Cmin ss) for Part 2. Cmin was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 2 only: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours
Cavg
PK parameter: Average Plasma Concentration (Cavg) for Part 2. Cavg was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 2 only: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours.
Tmax, ss
PK parameter: Time When The Maximal Concentration Is Observed at Steady State (Tmax, ss) for Part 2. Tmax, ss was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 2 only: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours.
AUC0-τ (AUC0-24 at Day 12 Dose) for Part 2
PK parameter: Area Under The Concentration-Time Curve For One Dosing Interval (Τ) (AUC0-τ) \[i.e., AUC0-24 on Day 12 dose\] for Part 2 only. Value was calculated based on several PK blood sampling at times provided in the Outcome Measure Time Frame.
Time frame: Part 2 only: Day 12 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours.
AUC0-t on Day 1 Dose for Part 2
PK parameter: Area Under The Concentration-Time Curve AUC0-t (i.e., AUC0-24 on Day 1 dose only) for Part 2
Time frame: Part 2 only: Day 1 Pre-dose (within 2 hours of dosing) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, and 96 hours.