A Study Assessing the Safety of Oral ATH-399A in Healthy Adult Participants

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

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 Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: ATH-399A; Drug: Placebo; Drug: 20mg ATH-399A capsule; Drug: ATH-399A 10 mg; Drug: 5 mg ATH-399A capsule; Drug: 40mg ATH-399A capsule; Drug: 80mg ATH-399A capsule

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, QC G1P 0A2
    • Syneos Quebec Canada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy, as determined by the Investigator based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests, and cardiac monitoring.

2. Population

   1. Part 1a and 1b: Men and women, age 18-55 years inclusive at the date of screening.
   2. 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.
3. Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating.
4. Postmenopausal women must have had ≥12 months of spontaneous amenorrhea (with follicle-stimulating hormone [FSH] ≥40 milli-international units per milliliter (mIU/mL)).
5. 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.

6. Male participants who are sexually active with WOCBP must:

   1. 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
   2. 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.
7. 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).
8. Participants participating in Part 1b must be willing and able to consume the entire high-fat, high-calorie breakfast in the designated timeframe.
9. Participants must understand the nature of the study, must be willing to participate in the study, and must provide signed and dated written informed consent in accordance with local regulations before the conduct of any study-related procedures.
10. Participants must be, in the opinion of the Investigator, able to participate in all scheduled evaluations, likely to complete all required tests, and likely to be compliant.
11. Participants must be fluent in English or French.
12. Participants must agree not to post any personal medical data related to the study or information related to the study on any website or social media site.

Exclusion Criteria:

1. A positive urine cotinine, drug screen, or alcohol breath test at screening or Day -1.
2. 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.
3. 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.
4. A diagnosis of intellectual disability (intellectual developmental disorder) or mental retardation.
5. 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.
6. 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.
7. A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
8. A positive test at screening for human immunodeficiency virus (HIV) antigen or antibody or a history of positive test.
9. Alanine aminotransferase or aspartate aminotransferase levels greater than 1.2 times the ULN at screening or Day -1.
10. 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).
11. History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).
12. Regularly consumed (e.g., more days than not) excessive quantities of xanthine-containing beverages (e.g., more than 2 cups of coffee or the equivalent per day) within 1 week prior to screening or between screening and first dose administration, or unwillingness to refrain from xanthine-containing beverages during the in-clinic stay.
13. Received or used an investigational product (including placebo) or device within the following time period prior to the first dosing day in the current study: 30 days or 5 half-lives (whichever is longer). For biological products, administration of a biological product within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
14. Other than those medications outlined in the protocol body and those allowed in the MAD additional cohort, use of prescription or non-prescription drugs, herbal, and dietary supplements (including St John's Wort) within 7 days (or 28 days if the drug is a potential hepatic enzyme inducer) or 5 half-lives (whichever is longer) prior to first dose administration, unless in the opinion of the Investigator and Medical Monitor, the medication will not interfere with the study procedures or compromise participant safety.
15. History of clinically significant sensitivity to any of the study drugs, or components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
16. Donation of plasma within 7 days prior to the first dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to the first dosing.
17. A positive pregnancy test or lactation.
18. A history or presence of any disease, condition, or surgery likely to affect drug absorption, distribution, metabolism, or excretion. Participants with a history of cholecystectomy should be excluded.
19. A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, pulmonary, ophthalmologic, immunologic, hematologic, dermatologic, or neurologic abnormality. Participants with fully resolved childhood asthma with no hospitalizations or recurrence in adulthood are permitted to enroll. For the additional cohort in Part 2, any of the above is acceptable where the condition is stable for >6 months and, in the opinion of the Investigator, it does not impact participant safety.
20. A clinically significant abnormality on physical examination, neurological examination, electrocardiogram (ECG), or laboratory evaluations at screening and Day -1.
21. A QT interval measurement corrected according to the Fridericia rule (QTcF) > 450 milliseconds (msec) during controlled rest at screening and Day -1, or family history of long QT syndrome.
22. Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgment of the Investigator or Medical Monitor, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
23. A clinically significant vital sign abnormality at screening or between screening and first dose administration.
24. Significant (> 10%) weight loss or gain within 30 days prior to screening or between screening and first dose administration.
25. A history of seizures. The occurrence of a single febrile seizure is not exclusionary.
26. A history of head trauma, including closed head injury with loss of consciousness. Concussions which did not lead to hospitalization or loss of consciousness, and for which there are no ongoing issues, are not exclusionary.
27. A history of symptomatic orthostatic hypotension (i.e., postural syncope).
28. A history of neuroleptic malignant syndrome.
29. A history of chronic urinary tract infections (≥2 times per year).
30. The participant is, in the opinion of the Investigator or Medical Monitor, unlikely to comply with the protocol or is unsuitable for any reason.
31. Currently employed by NurrOn Pharmaceuticals, Inc., HanAll Biopharma Co. Ltd., or HanAll Pharmaceutical Inc., or by a clinical trial site participating in this study, or a first-degree relative of a NurrOn Pharmaceuticals, Inc. or HanAll Pharmaceutical Inc., or HanAll Biopharma Co. Ltd. employee or of an employee at a participating clinical trial site.
32. Unsatisfactory venous access.
33. Unable to swallow oral capsules.
34. Positive result to a coronavirus disease (COVID-19) Polymerase chain reaction (PCR) test.
35. COVID-19 or flu vaccination within 30 days prior to study drug administration or any other vaccination that is judged by the investigator to potentially affect eligibility.
36. Presence of fever (body temperature >37.5°C) (e.g., a fever associated with a symptomatic viral or bacterial infection) within 2 weeks prior to the first dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 1a (SAD): Placebo; Participants will receive single oral dose of placebo-matched to ATH-399A capsule.	Drug: Placebo; Orally administered drug in capsule form.
Experimental: 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.	Drug: ATH-399A; Orally administered drug in capsule form.; Other Names: ATH-399A, HL192
Experimental: 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.	Drug: ATH-399A; Orally administered drug in capsule form.; Other Names: ATH-399A, HL192
Experimental: 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.	Drug: ATH-399A; Orally administered drug in capsule form.; Other Names: ATH-399A, HL192
Placebo Comparator: 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.	Drug: Placebo; Orally administered drug in capsule form.
Experimental: 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.	Drug: ATH-399A; Orally administered drug in capsule form.; Other Names: ATH-399A, HL192
Placebo Comparator: 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.	Drug: Placebo; Orally administered drug in capsule form.
Experimental: Part 1a (Single Ascending Doses (SAD)): ATH-399A; Participants will receive single oral dose of ATH-399A capsule at 5mg, 10mg, 20mg, 40mg, 80mg.	Drug: ATH-399A; Orally administered drug in capsule form.; Other Names: ATH-399A, HL192
Experimental: Part 1a - ATH-399A 20 mg; Participants will receive single oral dose of 20mg of ATH-399A capsule	Drug: 20mg ATH-399A capsule; Participants will receive single oral dose of 20mg of ATH-399A capsule
Experimental: Part 1a (Single Ascending Doses (SAD)): ATH-399A 10 mg; Participants will receive single oral dose of 10mg of ATH-399A capsule	Drug: ATH-399A 10 mg; Participants will receive single oral dose of 10 mg of ATH-399A capsule
Experimental: Part 1a (Single Ascending Doses (SAD)): ATH-399A 5 mg; Participants will receive single oral dose of 5mg of ATH-399A capsule	Drug: 5 mg ATH-399A capsule; Participants will receive single oral dose of 5mg of ATH-399A capsule
Experimental: Part 1a (Single Ascending Doses (SAD)): ATH-399A 40 mg; Participants will receive single oral dose of 40mg of ATH-399A capsule	Drug: 40mg ATH-399A capsule; Participants will receive single oral dose of 40mg of ATH-399A capsule
Experimental: Part 1a (Single Ascending Doses (SAD)): ATH-399A 80 mg; Participants will receive single oral dose of 80mg of ATH-399A capsule	Drug: 80mg ATH-399A capsule; Participants will receive single oral dose of 80mg of ATH-399A capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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)	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	Diastolic blood pressure baseline value measured at basline Day 1 pre dose and Day 1 1 hour post dosing	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	Day 1 predose and 1 hour postdosing
Heart Rate Value	Heart rate value measured at Day 1, 1 Hour Post-Dose	Day 1, 1 hour post-dose
Temperature Value	Temperature value measured at Day 1, 1 Hour Post-Dose	Day 1, 1 Hour Post-Dose
Respiratory Rate Value	Respiratory rate value measured at Day 1, 1 Hour Post-Dose	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)	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)	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	Day 1
Laboratory Parameter: Glucose	Laboratory parameter: Glucose level measured on Day 1	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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	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.

Collaborators and Investigators

• Sponsor: HanAll BioPharma Co., Ltd.
• Collaborators: NurrOn Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2023
• Primary Completion (Actual): April 24, 2024
• Study Completion (Actual): April 24, 2024

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Parkinson's Disease; ATH399A; HL192
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: HL192-PD-CA-P101; 230119 (Other Identifier: Syneos Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No