A Study Assessing the Safety of Oral ATH-399A in Healthy... | NCT06088784

NCT06088784

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
230119	Other Identifier	Syneos Health

Status Module

Sponsor/Collaborators Module

Name	Class
NurrOn Pharmaceuticals, Inc.	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ATH-399A	Drug	Orally administered drug in capsule form.	Additional Cohort (Ages 56-80 years old): ATH-399A Part 1a (Single Ascending Doses (SAD)): ATH-399A

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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.

Eligibility Module

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.
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.
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:
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.
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.
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:

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.
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.
A positive pregnancy test or lactation.
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.
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.
A clinically significant abnormality on physical examination, neurological examination, electrocardiogram (ECG), or laboratory evaluations at screening and Day -1.
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.
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.
A clinically significant vital sign abnormality at screening or between screening and first dose administration.
Significant (> 10%) weight loss or gain within 30 days prior to screening or between screening and first dose administration.
A history of seizures. The occurrence of a single febrile seizure is not exclusionary.
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.
A history of symptomatic orthostatic hypotension (i.e., postural syncope).
A history of neuroleptic malignant syndrome.
A history of chronic urinary tract infections (≥2 times per year).
The participant is, in the opinion of the Investigator or Medical Monitor, unlikely to comply with the protocol or is unsuitable for any reason.
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.
Unsatisfactory venous access.
Unable to swallow oral capsules.
Positive result to a coronavirus disease (COVID-19) Polymerase chain reaction (PCR) test.
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.
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

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Syneos Quebec Canada		Québec		QC G1P 0A2	Canada

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Part 1a: 40 participants randomized Part 1b: 12 participants randomized Part 2: 24 participants randomized

Arm/Group Information

ID	Title	Description
FG000	Part 1a (SAD): ATH-399A 5 mg	Each participant received a single oral dose of 5 mg of ATH-399A.
FG001	Part 1a (SAD): ATH-399A 10 mg	Each participant received a single oral dose of 10 mg of ATH-399A.
FG002	Part 1a (SAD): ATH-399A 20 mg	Each participant received a single oral dose of 20 mg of ATH-399A.
FG003	Part 1a (SAD): ATH-399A 40 mg	Each participant received a single oral dose of 40 mg of ATH-399A.
FG004	Part 1a (SAD): ATH-399A 80 mg	Each participant received a single oral dose of 80 mg of ATH-399A.
FG005	Part 1a (SAD): Placebo	Each participant received a single dose of matching placebo.
FG006	Part 1b (Food Effect): ATH-399A 40 mg, Sequence AB	Participants in Part 1b were randomized to one of the 2 arms to receive study drugs in the cross-over sequence AB or BA. Treatment A: ATH-399A 40 mg was administered following a high-fat, high-calorie meal. Treatment B: Participants were restricted from eating 10 hours prior to and 4 hours following ATH-399A 40 mg administration.
FG007	Part 1b (Food Effect): ATH-399A 40 mg, Sequence BA	Participants in Part 1b were randomized to one of the 2 arms to receive study drugs in the cross-over sequence AB or BA. Treatment A: ATH-399A 40 mg was administered following a high-fat, high-calorie meal. Treatment B: Participants were restricted from eating 10 hours prior to and 4 hours following ATH-399A 40 mg administration.
FG008	Part 2 (MAD): ATH-399A 20 mg	Each participant received ATH-399A 20 mg once daily from Day 1 to Day 12. Participants underwent a supervised fast for at least 10 hours prior to dosing, followed by an additional 4 hours of fasting post-dose.
FG009	Part 2 (MAD): ATH-399A 40 mg	Each participant received ATH-399A 40 mg once daily from Day 1 to Day 12. Participants underwent a supervised fast for at least 10 hours prior to dosing, followed by an additional 4 hours of fasting post-dose.
FG010	Part 2 (MAD): ATH-399A 40 mg, Older	Each participant aged >55-80 years received ATH-399A 40 mg once daily from Day 1 to Day 12. Participants underwent a supervised fast for at least 10 hours prior to dosing, followed by an additional 4 hours of fasting post-dose.
FG011	Part 2 (MAD): Placebo	Each participant received a single dose of matching placebo.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0006 subjects FG0016 subjects FG0026 subjects FG0036 subjects FG0046 subjects FG00510 subjects FG0066 subjects FG0076 subjects FG0086 subjects FG0096 subjects FG0106 subjects FG0116 subjects
COMPLETED		FG0006 subjects FG0016 subjects FG0026 subjects FG0036 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part 1a (SAD): ATH-399A 5 mg	Each participant received a single oral dose of 5 mg of ATH-399A.
BG001	Part 1a (SAD): ATH-399A 10 mg	Each participant received a single oral dose of 10 mg of ATH-399A.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Number

Treatment Emergent Adverse Event

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

ID	Title	Description
OG000	Part 1a (SAD): ATH-399A 5 mg	Each participant received a single oral dose of 5 mg of ATH-399A.
OG001	Part 1a (SAD): ATH-399A 10 mg	Each participant received a single oral dose of 10 mg of ATH-399A.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1a (SAD): ATH-399A 5 mg	Each participant received a single oral dose of 5 mg of ATH-399A.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
COVID-19, conjunctivitis, asymptomatic bacteriuria, nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Sr. Director, Clinical Development Operations	HPI, Inc.	301-738-3980		mary.bearkland@hanall.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 26, 2024	Apr 18, 2025	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Nov 30, 2023	Apr 18, 2025	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D010300	Parkinson Disease

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Part 1b (Fasting): ATH-399A

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

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

EG0001 events1 affected6 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected6 at risk
EG0040 events0 affected6 at risk
EG0050 events0 affected10 at risk
EG0060 events0 affected12 at risk
EG0071 events1 affected8 at risk
EG0080 events0 affected6 at risk
EG0090 events0 affected6 at risk
EG0101 events1 affected6 at risk
EG0111 events1 affected6 at risk

OG0041093.98± 274.05

OG005651.13± 179.31

OG006569.69± 189.58

OG007450.52± 124.54

OG0081337.49± 577.26

OG0091601.07± 476.59

OG0041200.69± 320.04

OG005720.93± 211.31

OG006625.05± 209.54

OG007485.14± 134.00

OG0081454.58± 629.97

OG0091782.88± 504.10

OG0098.017(2 to 23.517)

OG0040.0250± 0.0041

OG0050.0253± 0.0052

OG0060.0261± 0.0047

OG0070.0286± 0.0041

OG0080.0264± 0.0026

OG0090.0235± 0.0028