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

NCT06088784 | Completed Phase 1 Results DMC

• 2 other identifiers: HL192-PD-CA-P101230119
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

ATH399A; HL192; Parkinson's Disease

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (12)

• 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.

Study Arms (13)

Part 1a (Single Ascending Doses (SAD)): ATH-399A

EXPERIMENTAL

Participants will receive single oral dose of ATH-399A capsule at 5mg, 10mg, 20mg, 40mg, 80mg.

Drug: ATH-399A

Part 1a (SAD): Placebo

PLACEBO COMPARATOR

Participants will receive single oral dose of placebo-matched to ATH-399A capsule.

Drug: Placebo

Part 1b (High calorie): ATH-399A

EXPERIMENTAL

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

Part 1b (Fasting): ATH-399A

EXPERIMENTAL

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

Part 2 (Multiple Ascending doses (MAD)): ATH-399A

EXPERIMENTAL

Participants will receive once daily (QD) dose of ATH-399A capsules from Day 1 to Day 12 in fasted state.

Drug: ATH-399A

Part 2 (MAD): Placebo

PLACEBO COMPARATOR

Participants will receive QD dose of placebo-matched to ATH-399A capsules from Day 1 to Day 12 in fasted state.

Drug: Placebo

Additional Cohort (Ages 56-80 years old): ATH-399A

EXPERIMENTAL

Participants will receive QD dose of ATH-399A capsules from Day 1 to Day 12 in fasted state following MAD dosing.

Drug: ATH-399A

Additional Cohort: (Ages 56-80 years old) Placebo

PLACEBO COMPARATOR

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

Part 1a - ATH-399A 20 mg

EXPERIMENTAL

Participants will receive single oral dose of 20mg of ATH-399A capsule

Drug: 20mg ATH-399A capsule

Part 1a (Single Ascending Doses (SAD)): ATH-399A 10 mg

EXPERIMENTAL

Participants will receive single oral dose of 10mg of ATH-399A capsule

Drug: ATH-399A 10 mg

Part 1a (Single Ascending Doses (SAD)): ATH-399A 5 mg

EXPERIMENTAL

Participants will receive single oral dose of 5mg of ATH-399A capsule

Drug: 5 mg ATH-399A capsule

Part 1a (Single Ascending Doses (SAD)): ATH-399A 40 mg

EXPERIMENTAL

Participants will receive single oral dose of 40mg of ATH-399A capsule

Drug: 40mg ATH-399A capsule

Part 1a (Single Ascending Doses (SAD)): ATH-399A 80 mg

EXPERIMENTAL

Participants will receive single oral dose of 80mg of ATH-399A capsule

Drug: 80mg ATH-399A capsule

Interventions

ATH-399A DRUG

Orally administered drug in capsule form.

Also known as: ATH-399A, HL192

Additional Cohort (Ages 56-80 years old): ATH-399A; Part 1a (Single Ascending Doses (SAD)): ATH-399A; Part 1b (Fasting): ATH-399A; Part 1b (High calorie): ATH-399A; Part 2 (Multiple Ascending doses (MAD)): ATH-399A

Placebo DRUG

Orally administered drug in capsule form.

Additional Cohort: (Ages 56-80 years old) Placebo; Part 1a (SAD): Placebo; Part 2 (MAD): Placebo

ATH-399A 10 mg DRUG

Participants will receive single oral dose of 10 mg of ATH-399A capsule

Part 1a (Single Ascending Doses (SAD)): ATH-399A 10 mg

5 mg ATH-399A capsule DRUG

Participants will receive single oral dose of 5mg of ATH-399A capsule

Part 1a (Single Ascending Doses (SAD)): ATH-399A 5 mg

20mg ATH-399A capsule DRUG

Participants will receive single oral dose of 20mg of ATH-399A capsule

Part 1a - ATH-399A 20 mg

40mg ATH-399A capsule DRUG

Participants will receive single oral dose of 40mg of ATH-399A capsule

Part 1a (Single Ascending Doses (SAD)): ATH-399A 40 mg

80mg ATH-399A capsule DRUG

Participants will receive single oral dose of 80mg of ATH-399A capsule

Part 1a (Single Ascending Doses (SAD)): ATH-399A 80 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, as determined by the Investigator based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests, and cardiac monitoring.
• Population
• 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).
• Participants participating in Part 1b must be willing and able to consume the entire high-fat, high-calorie breakfast in the designated timeframe.
• 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.
• 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.
• Participants must be fluent in English or French.

You may not qualify if:

• A positive urine cotinine, drug screen, or alcohol breath test at screening or Day -1.
• 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 -1.
• 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).
• 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%).
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• HanAll BioPharma Co., Ltd.: lead
• NurrOn Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Syneos Quebec Canada

Québec, QC G1P 0A2, Canada

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Sr. Director, Clinical Development Operations
• Organization: HPI, Inc.

mary.bearkland@hanall.com

301-738-3980

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Parts 1a and 2 are double-blind and Part 1b is open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 18, 2023
• Study Start: September 19, 2023
• Primary Completion: April 24, 2024
• Study Completion: April 24, 2024
• Last Updated: December 19, 2025
• Results First Posted: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)