A Randomized, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics of Single and Multiple Doses as Well as the Food Effect of Orally Administered ATH-399A in Healthy Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- ATH-399A
- Conditions
- Healthy Volunteers
- Sponsor
- HanAll BioPharma Co., Ltd.
- Enrollment
- 76
- Locations
- 1
- Primary Endpoint
- Number of TEAEs
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, as determined by the Investigator based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests, and cardiac monitoring.
- •Part 1a and 1b: Men and women, age 18-55 years inclusive at the date of screening.
- •Part 2: Men and women aged 18-55 years inclusive at the date of screening. Additional cohort: Participants of the additional cohort will be of approximately equal numbers of male and post-menopausal or surgically sterile females, with a minimum of 2 of each gender, aged \>55-80 years, inclusive.
- •Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating.
- •Postmenopausal women must have had ≥12 months of spontaneous amenorrhea (with follicle-stimulating hormone \[FSH\] ≥40 milli-international units per milliliter (mIU/mL)).
- •Surgically sterile women are defined as those who have had a hysterectomy and/or bilateral oophorectomy. Women who are surgically sterile must provide verbal confirmation.
- •Male participants who are sexually active with WOCBP must:
- •Agree to use condoms to protect their partners from becoming pregnant during the study (including washout periods) and not to donate sperm for at least 90 days after the last dose of the study drug, and
- •Agree to ensure that they and their partners are routinely using a medically approved contraceptive method. It is important that male participants not impregnate others while in the study.
- •Body weight ≥50.0 kilograms (kg) for men and ≥45.0 kg for women and body mass index within the range of 18.0-30.0 kilogram/square meter (kg/m\^2) (inclusive).
Exclusion Criteria
- •A positive urine cotinine, drug screen, or alcohol breath test at screening or Day -
- •Any history of psychiatric disorders, including substance use disorders, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria that requires current treatment with psychiatric medications. Participants with mild anxiety or depression which is stable for \>6 months are permitted.
- •History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine \[PCP\], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
- •A diagnosis of intellectual disability (intellectual developmental disorder) or mental retardation.
- •A serious mental illness, dementia, or other neuropsychiatric disorder that would interfere with participation in the trial, or ability to provide informed consent in the opinion of the Investigator.
- •Any active suicidal ideation as indicated by the C-SSRS (score of ≥4) or history of suicidal behavior within the 12 months prior to screening.
- •A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
- •A positive test at screening for human immunodeficiency virus (HIV) antigen or antibody or a history of positive test.
- •Alanine aminotransferase or aspartate aminotransferase levels greater than 1.2 times the ULN at screening or Day -
- •Frequently use (\>5 per week) any tobacco-containing (e.g., cigar, cigarette or snuff) or nicotine-containing product (e.g., nicotine chewing gum, nicotine plasters, or other product used for smoking cessation) within 30 days prior to the first dose administration. Use of any tobacco- or nicotine-containing product is prohibited within 2 weeks of first dose administration through completion of the in-clinic stay for the SAD (Parts 1a and 1b) and until after the final study visit for the MAD (Part 2).
Arms & Interventions
Part 1a (Single Ascending Doses (SAD)): ATH-399A
Participants will receive single oral dose of ATH-399A capsule at 5mg, 10mg, 20mg, 40mg, 80mg.
Intervention: ATH-399A
Part 1a (SAD): Placebo
Participants will receive single oral dose of placebo-matched to ATH-399A capsule.
Intervention: Placebo
Part 1b (High calorie): ATH-399A
Participants will receive single oral dose of ATH-399A capsule after high-calorie, high-fat breakfast and then will cross over to receive single oral dose of ATH-399A capsule after fasting.
Intervention: ATH-399A
Part 1b (Fasting): ATH-399A
Participants will receive single oral dose of ATH-399A capsule after fasting and then will cross over to receive single oral dose of ATH-399A capsule after high-calorie, high-fat breakfast.
Intervention: ATH-399A
Part 2 (Multiple Ascending doses (MAD)): ATH-399A
Participants will receive once daily (QD) dose of ATH-399A capsules from Day 1 to Day 12 in fasted state.
Intervention: ATH-399A
Part 2 (MAD): Placebo
Participants will receive QD dose of placebo-matched to ATH-399A capsules from Day 1 to Day 12 in fasted state.
Intervention: Placebo
Additional Cohort (Ages 56-80 years old): ATH-399A
Participants will receive QD dose of ATH-399A capsules from Day 1 to Day 12 in fasted state following MAD dosing.
Intervention: ATH-399A
Additional Cohort: (Ages 56-80 years old) Placebo
Participants will receive QD dose of placebo-matched to ATH-399A capsules from Day 1 to Day 12 in fasted state following MAD dosing.
Intervention: Placebo
Part 1a - ATH-399A 20 mg
Participants will receive single oral dose of 20mg of ATH-399A capsule
Intervention: 20mg ATH-399A capsule
Part 1a (Single Ascending Doses (SAD)): ATH-399A 10 mg
Participants will receive single oral dose of 10mg of ATH-399A capsule
Intervention: ATH-399A 10 mg
Part 1a (Single Ascending Doses (SAD)): ATH-399A 5 mg
Participants will receive single oral dose of 5mg of ATH-399A capsule
Intervention: 5 mg ATH-399A capsule
Part 1a (Single Ascending Doses (SAD)): ATH-399A 40 mg
Participants will receive single oral dose of 40mg of ATH-399A capsule
Intervention: 40mg ATH-399A capsule
Part 1a (Single Ascending Doses (SAD)): ATH-399A 80 mg
Participants will receive single oral dose of 80mg of ATH-399A capsule
Intervention: 80mg ATH-399A capsule
Outcomes
Primary Outcomes
Number of TEAEs
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
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.
Participants With at Least 1 TEAE
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 one AE started or after the time of first study drug administration.
Serious TEAEs
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
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.
Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS)
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)
Number of participant whose answers indicate suicidal ideation and/or behavior at follow-up.
QTcF Analysis
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
Participants with abnormal QTcF on ECG (pooled data from the whole study duration)
Changes in Diastolic Blood Pressure
Time Frame: Day 1: predose and 1 hour post dosing
Diastolic blood pressure baseline value measured at basline Day 1 pre dose and Day 1 1 hour post dosing
Changes in Systolic Blood Pressure
Time Frame: Day 1 predose and 1 hour postdosing
Systolic blood pressure baseline value measured at basline Day 1 pre dose and Day 1 1 hour post dosing
Heart Rate Value
Time Frame: Day 1, 1 hour post-dose
Heart rate value measured at Day 1, 1 Hour Post-Dose
Temperature Value
Time Frame: Day 1, 1 Hour Post-Dose
Temperature value measured at Day 1, 1 Hour Post-Dose
Respiratory Rate Value
Time Frame: Day 1, 1 Hour Post-Dose
Respiratory rate value measured at Day 1, 1 Hour Post-Dose
Physical Examination and Neurological Examination Abnormalities Analysis
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
Participants with abnormal findings on physical and neurological examination (pooled data from the whole study)
12-Lead Telemetry Abnormalities Analysis
Time Frame: Part 1a, 1b: D1, D2, D3; Part 2: D1, D2, D12, D13 (Discharge or early termination)
Participants with abnormal findings on 12-lead telemetry (pooled data from the whole study)
Laboratory Parameter: Creatinine Value
Time Frame: Day 1
Laboratory parameter: Creatinine level on Day 1
Laboratory Parameter: Glucose
Time Frame: Day 1
Laboratory parameter: Glucose level measured on Day 1
Secondary Outcomes
- AUC0-t(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(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(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(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(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(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(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(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(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(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(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(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.)