Healthy Volunteers
Conditions
Keywords
ATH399A, HL192, Parkinson's Disease
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.
Interventions
DRUGATH-399A
Orally administered drug in capsule form.
DRUGPlacebo
Orally administered drug in capsule form.
DRUGATH-399A 10 mg
Participants will receive single oral dose of 10 mg of ATH-399A capsule
DRUG5 mg ATH-399A capsule
Participants will receive single oral dose of 5mg of ATH-399A capsule
DRUG20mg ATH-399A capsule
Participants will receive single oral dose of 20mg of ATH-399A capsule
DRUG40mg ATH-399A capsule
Participants will receive single oral dose of 40mg of ATH-399A capsule
DRUG80mg ATH-399A capsule
Participants will receive single oral dose of 80mg of ATH-399A capsule
Sponsors
NurrOn Pharmaceuticals, Inc.
HanAll BioPharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Parts 1a and 2 are double-blind and Part 1b is open label.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory Parameter: Glucose | Day 1 | Laboratory parameter: Glucose level measured on Day 1 |
| Changes in Systolic Blood Pressure | 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 |
| Number of TEAEs | 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 | 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 | 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) | 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 | 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 | 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 |
| Temperature Value | Day 1, 1 Hour Post-Dose | Temperature value measured at Day 1, 1 Hour Post-Dose |
| Respiratory Rate Value | Day 1, 1 Hour Post-Dose | Respiratory rate value measured at Day 1, 1 Hour Post-Dose |
| Physical Examination and Neurological Examination Abnormalities Analysis | 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 | 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 | Day 1 | Laboratory parameter: Creatinine level on Day 1 |
| Heart Rate Value | Day 1, 1 hour post-dose | Heart rate value measured at Day 1, 1 Hour Post-Dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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 | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | 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. |
| 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. | PK parameter: Area Under The Concentration-Time Curve AUC0-t (i.e., AUC0-24 on Day 1 dose only) for Part 2 |
| 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. | 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. |
Countries
Canada
Participant flow
Pre-assignment details
Part 1a: 40 participants randomized Part 1b: 12 participants randomized Part 2: 24 participants randomized
Participants by arm
| Arm | Count |
|---|---|
| Part 1a (SAD): ATH-399A 5 mg Each participant received a single oral dose of 5 mg of ATH-399A. | 6 |
| Part 1a (SAD): ATH-399A 10 mg Each participant received a single oral dose of 10 mg of ATH-399A. | 6 |
| Part 1a (SAD): ATH-399A 20 mg Each participant received a single oral dose of 20 mg of ATH-399A. | 6 |
| Part 1a (SAD): ATH-399A 40 mg Each participant received a single oral dose of 40 mg of ATH-399A. | 6 |
| Part 1a (SAD): ATH-399A 80 mg Each participant received a single oral dose of 80 mg of ATH-399A. | 6 |
| Part 1a (SAD): Placebo Each participant received a single dose of matching placebo. | 10 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| Part 2 (MAD): Placebo Each participant received a single dose of matching placebo. | 6 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Exclusion criterion: QTcF >450 msec | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1a (SAD): ATH-399A 5 mg | Part 1a (SAD): ATH-399A 10 mg | Part 1a (SAD): ATH-399A 20 mg | Part 1a (SAD): ATH-399A 40 mg | Part 1a (SAD): ATH-399A 80 mg | Part 1a (SAD): Placebo | Part 1b (Food Effect): ATH-399A 40 mg, Sequence AB | Part 1b (Food Effect): ATH-399A 40 mg, Sequence BA | Part 2 (MAD): ATH-399A 20 mg | Part 2 (MAD): ATH-399A 40 mg | Part 2 (MAD): ATH-399A 40 mg, Older | Part 2 (MAD): Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 36.7 years STANDARD_DEVIATION 8.07 | 35.5 years STANDARD_DEVIATION 10.8 | 50.0 years STANDARD_DEVIATION 5.29 | 39.0 years STANDARD_DEVIATION 8.88 | 42.8 years STANDARD_DEVIATION 5.46 | 39.2 years STANDARD_DEVIATION 8.88 | 37.0 years STANDARD_DEVIATION 13.34 | 41.5 years STANDARD_DEVIATION 10.05 | 35.7 years STANDARD_DEVIATION 11.72 | 47.0 years STANDARD_DEVIATION 6.96 | 64.8 years STANDARD_DEVIATION 5.31 | 50.2 years STANDARD_DEVIATION 12.64 | 43.07 years STANDARD_DEVIATION 11.8292 |
| Body Mass Index (BMI) | 24.72 kg/m2 STANDARD_DEVIATION 3.277 | 24.50 kg/m2 STANDARD_DEVIATION 1.971 | 23.97 kg/m2 STANDARD_DEVIATION 3.236 | 25.48 kg/m2 STANDARD_DEVIATION 3.388 | 26.03 kg/m2 STANDARD_DEVIATION 3.027 | 24.16 kg/m2 STANDARD_DEVIATION 2.476 | 25.90 kg/m2 STANDARD_DEVIATION 3.551 | 24.60 kg/m2 STANDARD_DEVIATION 3.529 | 24.22 kg/m2 STANDARD_DEVIATION 3.573 | 26.93 kg/m2 STANDARD_DEVIATION 1.507 | 23.87 kg/m2 STANDARD_DEVIATION 2.889 | 24.93 kg/m2 STANDARD_DEVIATION 2.479 | 24.90 kg/m2 STANDARD_DEVIATION 2.873 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 10 Participants | 3 Participants | 4 Participants | 6 Participants | 3 Participants | 5 Participants | 4 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 168.67 cm STANDARD_DEVIATION 8.134 | 171.08 cm STANDARD_DEVIATION 6.931 | 163.73 cm STANDARD_DEVIATION 8.188 | 176.57 cm STANDARD_DEVIATION 9.528 | 168.33 cm STANDARD_DEVIATION 6.439 | 166.70 cm STANDARD_DEVIATION 12.541 | 170.92 cm STANDARD_DEVIATION 8.357 | 167.68 cm STANDARD_DEVIATION 7.427 | 172.70 cm STANDARD_DEVIATION 10.05 | 171.83 cm STANDARD_DEVIATION 7.757 | 170.68 cm STANDARD_DEVIATION 7.105 | 174.25 cm STANDARD_DEVIATION 8.802 | 170.08 cm STANDARD_DEVIATION 8.8719 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 6 Participants | 3 Participants | 6 Participants | 10 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 68 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 4 Participants | 0 Participants | 4 Participants | 6 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 32 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 2 Participants | 6 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 5 Participants | 3 Participants | 4 Participants | 44 Participants |
| Weight | 70.43 kg STANDARD_DEVIATION 11.316 | 71.83 kg STANDARD_DEVIATION 7.689 | 64.52 kg STANDARD_DEVIATION 11.874 | 79.93 kg STANDARD_DEVIATION 15.591 | 74.25 kg STANDARD_DEVIATION 12.798 | 67.15 kg STANDARD_DEVIATION 9.957 | 76.12 kg STANDARD_DEVIATION 14.787 | 69.20 kg STANDARD_DEVIATION 11.516 | 72.87 kg STANDARD_DEVIATION 15.164 | 79.92 kg STANDARD_DEVIATION 10.198 | 69.92 kg STANDARD_DEVIATION 11.94 | 76.10 kg STANDARD_DEVIATION 12.381 | 72.39 kg STANDARD_DEVIATION 12.1717 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 12 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 6 | 1 / 6 | 1 / 6 | 2 / 6 | 1 / 6 | 2 / 10 | 3 / 12 | 1 / 8 | 3 / 6 | 2 / 6 | 3 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 12 | 0 / 8 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | 12-Lead Telemetry Abnormalities Analysis | 2 Participants |
| Part 1a (SAD): ATH-399A 10 mg | 12-Lead Telemetry Abnormalities Analysis | 1 Participants |
| Part 1a (SAD): ATH-399A 20 mg | 12-Lead Telemetry Abnormalities Analysis | 1 Participants |
| Part 1a (SAD): ATH-399A 40 mg | 12-Lead Telemetry Abnormalities Analysis | 1 Participants |
| Part 1a (SAD): ATH-399A 80 mg | 12-Lead Telemetry Abnormalities Analysis | 2 Participants |
| Part 1a (SAD): Placebo | 12-Lead Telemetry Abnormalities Analysis | 2 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | 12-Lead Telemetry Abnormalities Analysis | 5 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | 12-Lead Telemetry Abnormalities Analysis | 2 Participants |
| Part 2 (MAD): ATH-399A 20 mg | 12-Lead Telemetry Abnormalities Analysis | 3 Participants |
| Part 2 (MAD): ATH-399A 40 mg | 12-Lead Telemetry Abnormalities Analysis | 1 Participants |
| Part 2 (MAD): ATH-399A 40 mg, Older | 12-Lead Telemetry Abnormalities Analysis | 4 Participants |
| Part 2 (MAD): Placebo | 12-Lead Telemetry Abnormalities Analysis | 1 Participants |
Primary
Changes in Diastolic Blood Pressure
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Changes in Diastolic Blood Pressure | Baseline | 68.8 mmHg | Standard Deviation 7.73 |
| Part 1a (SAD): ATH-399A 5 mg | Changes in Diastolic Blood Pressure | 1 hour post dosing | 67.5 mmHg | Standard Deviation 6.35 |
| Part 1a (SAD): ATH-399A 10 mg | Changes in Diastolic Blood Pressure | Baseline | 70.8 mmHg | Standard Deviation 4.07 |
| Part 1a (SAD): ATH-399A 10 mg | Changes in Diastolic Blood Pressure | 1 hour post dosing | 69.2 mmHg | Standard Deviation 5.27 |
| Part 1a (SAD): ATH-399A 20 mg | Changes in Diastolic Blood Pressure | Baseline | 75.8 mmHg | Standard Deviation 7.39 |
| Part 1a (SAD): ATH-399A 20 mg | Changes in Diastolic Blood Pressure | 1 hour post dosing | 74.3 mmHg | Standard Deviation 6.74 |
| Part 1a (SAD): ATH-399A 40 mg | Changes in Diastolic Blood Pressure | 1 hour post dosing | 71.8 mmHg | Standard Deviation 6.91 |
| Part 1a (SAD): ATH-399A 40 mg | Changes in Diastolic Blood Pressure | Baseline | 70.7 mmHg | Standard Deviation 4.32 |
| Part 1a (SAD): ATH-399A 80 mg | Changes in Diastolic Blood Pressure | 1 hour post dosing | 70.5 mmHg | Standard Deviation 7.18 |
| Part 1a (SAD): ATH-399A 80 mg | Changes in Diastolic Blood Pressure | Baseline | 72.5 mmHg | Standard Deviation 7.87 |
| Part 1a (SAD): Placebo | Changes in Diastolic Blood Pressure | Baseline | 71.0 mmHg | Standard Deviation 6.46 |
| Part 1a (SAD): Placebo | Changes in Diastolic Blood Pressure | 1 hour post dosing | 70.7 mmHg | Standard Deviation 5.89 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Changes in Diastolic Blood Pressure | Baseline | 69.8 mmHg | Standard Deviation 6.12 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Changes in Diastolic Blood Pressure | 1 hour post dosing | 66.1 mmHg | Standard Deviation 6.1 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Changes in Diastolic Blood Pressure | 1 hour post dosing | 70.9 mmHg | Standard Deviation 6.13 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Changes in Diastolic Blood Pressure | Baseline | 69.0 mmHg | Standard Deviation 4.81 |
| Part 2 (MAD): ATH-399A 20 mg | Changes in Diastolic Blood Pressure | 1 hour post dosing | 71.8 mmHg | Standard Deviation 5.12 |
| Part 2 (MAD): ATH-399A 20 mg | Changes in Diastolic Blood Pressure | Baseline | 72.8 mmHg | Standard Deviation 3.19 |
| Part 2 (MAD): ATH-399A 40 mg | Changes in Diastolic Blood Pressure | Baseline | 72.0 mmHg | Standard Deviation 4 |
| Part 2 (MAD): ATH-399A 40 mg | Changes in Diastolic Blood Pressure | 1 hour post dosing | 70.8 mmHg | Standard Deviation 3.19 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Changes in Diastolic Blood Pressure | Baseline | 72.3 mmHg | Standard Deviation 1.97 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Changes in Diastolic Blood Pressure | 1 hour post dosing | 75.2 mmHg | Standard Deviation 3.19 |
| Part 2 (MAD): Placebo | Changes in Diastolic Blood Pressure | Baseline | 71.5 mmHg | Standard Deviation 7.77 |
| Part 2 (MAD): Placebo | Changes in Diastolic Blood Pressure | 1 hour post dosing | 73.0 mmHg | Standard Deviation 9.57 |
Primary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Changes in Systolic Blood Pressure | 1 hour post dosing | 105.8 mmHg | Standard Deviation 7.65 |
| Part 1a (SAD): ATH-399A 5 mg | Changes in Systolic Blood Pressure | baseline | 107.0 mmHg | Standard Deviation 7.21 |
| Part 1a (SAD): ATH-399A 10 mg | Changes in Systolic Blood Pressure | 1 hour post dosing | 110.8 mmHg | Standard Deviation 7.36 |
| Part 1a (SAD): ATH-399A 10 mg | Changes in Systolic Blood Pressure | baseline | 112.0 mmHg | Standard Deviation 4.2 |
| Part 1a (SAD): ATH-399A 20 mg | Changes in Systolic Blood Pressure | 1 hour post dosing | 117.0 mmHg | Standard Deviation 12.55 |
| Part 1a (SAD): ATH-399A 20 mg | Changes in Systolic Blood Pressure | baseline | 119.7 mmHg | Standard Deviation 12.37 |
| Part 1a (SAD): ATH-399A 40 mg | Changes in Systolic Blood Pressure | 1 hour post dosing | 113.8 mmHg | Standard Deviation 10.23 |
| Part 1a (SAD): ATH-399A 40 mg | Changes in Systolic Blood Pressure | baseline | 111.3 mmHg | Standard Deviation 5.24 |
| Part 1a (SAD): ATH-399A 80 mg | Changes in Systolic Blood Pressure | baseline | 111.8 mmHg | Standard Deviation 9.64 |
| Part 1a (SAD): ATH-399A 80 mg | Changes in Systolic Blood Pressure | 1 hour post dosing | 108.3 mmHg | Standard Deviation 11.04 |
| Part 1a (SAD): Placebo | Changes in Systolic Blood Pressure | 1 hour post dosing | 109.5 mmHg | Standard Deviation 9 |
| Part 1a (SAD): Placebo | Changes in Systolic Blood Pressure | baseline | 111.6 mmHg | Standard Deviation 9.13 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Changes in Systolic Blood Pressure | baseline | 111.4 mmHg | Standard Deviation 8.05 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Changes in Systolic Blood Pressure | 1 hour post dosing | 119.9 mmHg | Standard Deviation 13.99 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Changes in Systolic Blood Pressure | 1 hour post dosing | 116.5 mmHg | Standard Deviation 9.34 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Changes in Systolic Blood Pressure | baseline | 110.1 mmHg | Standard Deviation 7.83 |
| Part 2 (MAD): ATH-399A 20 mg | Changes in Systolic Blood Pressure | 1 hour post dosing | 114.7 mmHg | Standard Deviation 9.5 |
| Part 2 (MAD): ATH-399A 20 mg | Changes in Systolic Blood Pressure | baseline | 114.3 mmHg | Standard Deviation 5.39 |
| Part 2 (MAD): ATH-399A 40 mg | Changes in Systolic Blood Pressure | 1 hour post dosing | 113.8 mmHg | Standard Deviation 5.12 |
| Part 2 (MAD): ATH-399A 40 mg | Changes in Systolic Blood Pressure | baseline | 114.5 mmHg | Standard Deviation 9.97 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Changes in Systolic Blood Pressure | baseline | 116.3 mmHg | Standard Deviation 8.89 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Changes in Systolic Blood Pressure | 1 hour post dosing | 123.7 mmHg | Standard Deviation 11.43 |
| Part 2 (MAD): Placebo | Changes in Systolic Blood Pressure | baseline | 112.7 mmHg | Standard Deviation 11.47 |
| Part 2 (MAD): Placebo | Changes in Systolic Blood Pressure | 1 hour post dosing | 113.5 mmHg | Standard Deviation 9.38 |
Primary
Heart Rate Value
Heart rate value measured at Day 1, 1 Hour Post-Dose
Time frame: Day 1, 1 hour post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Heart Rate Value | 59.7 beats/min | Standard Deviation 10.27 |
| Part 1a (SAD): ATH-399A 10 mg | Heart Rate Value | 58.3 beats/min | Standard Deviation 6.09 |
| Part 1a (SAD): ATH-399A 20 mg | Heart Rate Value | 55.3 beats/min | Standard Deviation 5.16 |
| Part 1a (SAD): ATH-399A 40 mg | Heart Rate Value | 63.0 beats/min | Standard Deviation 10.81 |
| Part 1a (SAD): ATH-399A 80 mg | Heart Rate Value | 59.8 beats/min | Standard Deviation 6.05 |
| Part 1a (SAD): Placebo | Heart Rate Value | 64.7 beats/min | Standard Deviation 7.29 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Heart Rate Value | 65.3 beats/min | Standard Deviation 8.86 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Heart Rate Value | 60.6 beats/min | Standard Deviation 5.71 |
| Part 2 (MAD): ATH-399A 20 mg | Heart Rate Value | 62.3 beats/min | Standard Deviation 6.22 |
| Part 2 (MAD): ATH-399A 40 mg | Heart Rate Value | 58.7 beats/min | Standard Deviation 8.29 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Heart Rate Value | 63.0 beats/min | Standard Deviation 9.21 |
| Part 2 (MAD): Placebo | Heart Rate Value | 61.0 beats/min | Standard Deviation 7.46 |
Primary
Laboratory Parameter: Creatinine Value
Laboratory parameter: Creatinine level on Day 1
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Laboratory Parameter: Creatinine Value | 79.2 μmol/L | Standard Deviation 16.87 |
| Part 1a (SAD): ATH-399A 10 mg | Laboratory Parameter: Creatinine Value | 78.5 μmol/L | Standard Deviation 19.95 |
| Part 1a (SAD): ATH-399A 20 mg | Laboratory Parameter: Creatinine Value | 64.8 μmol/L | Standard Deviation 13.27 |
| Part 1a (SAD): ATH-399A 40 mg | Laboratory Parameter: Creatinine Value | 88.3 μmol/L | Standard Deviation 8.02 |
| Part 1a (SAD): ATH-399A 80 mg | Laboratory Parameter: Creatinine Value | 70.2 μmol/L | Standard Deviation 9.06 |
| Part 1a (SAD): Placebo | Laboratory Parameter: Creatinine Value | 76.6 μmol/L | Standard Deviation 10.86 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Laboratory Parameter: Creatinine Value | 76.5 μmol/L | Standard Deviation 15.26 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Laboratory Parameter: Creatinine Value | 76.4 μmol/L | Standard Deviation 16.37 |
| Part 2 (MAD): ATH-399A 20 mg | Laboratory Parameter: Creatinine Value | 87.5 μmol/L | Standard Deviation 14.46 |
| Part 2 (MAD): ATH-399A 40 mg | Laboratory Parameter: Creatinine Value | 111.2 μmol/L | Standard Deviation 15.43 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Laboratory Parameter: Creatinine Value | 84.0 μmol/L | Standard Deviation 11.24 |
| Part 2 (MAD): Placebo | Laboratory Parameter: Creatinine Value | 87.3 μmol/L | Standard Deviation 14.96 |
Primary
Laboratory Parameter: Glucose
Laboratory parameter: Glucose level measured on Day 1
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Laboratory Parameter: Glucose | 4.35 mmol/L | Standard Deviation 0.797 |
| Part 1a (SAD): ATH-399A 10 mg | Laboratory Parameter: Glucose | 4.07 mmol/L | Standard Deviation 0.585 |
| Part 1a (SAD): ATH-399A 20 mg | Laboratory Parameter: Glucose | 4.16 mmol/L | Standard Deviation 0.657 |
| Part 1a (SAD): ATH-399A 40 mg | Laboratory Parameter: Glucose | 4.62 mmol/L | Standard Deviation 0.983 |
| Part 1a (SAD): ATH-399A 80 mg | Laboratory Parameter: Glucose | 4.23 mmol/L | Standard Deviation 0.779 |
| Part 1a (SAD): Placebo | Laboratory Parameter: Glucose | 4.04 mmol/L | Standard Deviation 0.782 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Laboratory Parameter: Glucose | 4.95 mmol/L | Standard Deviation 0.894 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Laboratory Parameter: Glucose | 4.84 mmol/L | Standard Deviation 0.907 |
| Part 2 (MAD): ATH-399A 20 mg | Laboratory Parameter: Glucose | 4.43 mmol/L | Standard Deviation 0.441 |
| Part 2 (MAD): ATH-399A 40 mg | Laboratory Parameter: Glucose | 4.43 mmol/L | Standard Deviation 0.568 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Laboratory Parameter: Glucose | 3.85 mmol/L | Standard Deviation 0.356 |
| Part 2 (MAD): Placebo | Laboratory Parameter: Glucose | 4.58 mmol/L | Standard Deviation 0.313 |
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.
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Number of TEAEs | 4 Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 10 mg | Number of TEAEs | 2 Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 20 mg | Number of TEAEs | 1 Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 40 mg | Number of TEAEs | 3 Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 80 mg | Number of TEAEs | 2 Treatment Emergent Adverse Event |
| Part 1a (SAD): Placebo | Number of TEAEs | 3 Treatment Emergent Adverse Event |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Number of TEAEs | 3 Treatment Emergent Adverse Event |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Number of TEAEs | 1 Treatment Emergent Adverse Event |
| Part 2 (MAD): ATH-399A 20 mg | Number of TEAEs | 4 Treatment Emergent Adverse Event |
| Part 2 (MAD): ATH-399A 40 mg | Number of TEAEs | 2 Treatment Emergent Adverse Event |
| Part 2 (MAD): ATH-399A 40 mg, Older | Number of TEAEs | 10 Treatment Emergent Adverse Event |
| Part 2 (MAD): Placebo | Number of TEAEs | 6 Treatment Emergent Adverse Event |
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Participants With at Least 1 TEAE | 4 Participants |
| Part 1a (SAD): ATH-399A 10 mg | Participants With at Least 1 TEAE | 1 Participants |
| Part 1a (SAD): ATH-399A 20 mg | Participants With at Least 1 TEAE | 1 Participants |
| Part 1a (SAD): ATH-399A 40 mg | Participants With at Least 1 TEAE | 2 Participants |
| Part 1a (SAD): ATH-399A 80 mg | Participants With at Least 1 TEAE | 1 Participants |
| Part 1a (SAD): Placebo | Participants With at Least 1 TEAE | 2 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Participants With at Least 1 TEAE | 3 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Participants With at Least 1 TEAE | 1 Participants |
| Part 2 (MAD): ATH-399A 20 mg | Participants With at Least 1 TEAE | 3 Participants |
| Part 2 (MAD): ATH-399A 40 mg | Participants With at Least 1 TEAE | 2 Participants |
| Part 2 (MAD): ATH-399A 40 mg, Older | Participants With at Least 1 TEAE | 3 Participants |
| Part 2 (MAD): Placebo | Participants With at Least 1 TEAE | 2 Participants |
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Physical Examination and Neurological Examination Abnormalities Analysis | 2 Participants |
| Part 1a (SAD): ATH-399A 10 mg | Physical Examination and Neurological Examination Abnormalities Analysis | 2 Participants |
| Part 1a (SAD): ATH-399A 20 mg | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 1a (SAD): ATH-399A 40 mg | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 1a (SAD): ATH-399A 80 mg | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 1a (SAD): Placebo | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 2 (MAD): ATH-399A 20 mg | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 2 (MAD): ATH-399A 40 mg | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
| Part 2 (MAD): ATH-399A 40 mg, Older | Physical Examination and Neurological Examination Abnormalities Analysis | 1 Participants |
| Part 2 (MAD): Placebo | Physical Examination and Neurological Examination Abnormalities Analysis | 0 Participants |
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | QTcF Analysis | 0 Participants |
| Part 1a (SAD): ATH-399A 10 mg | QTcF Analysis | 0 Participants |
| Part 1a (SAD): ATH-399A 20 mg | QTcF Analysis | 0 Participants |
| Part 1a (SAD): ATH-399A 40 mg | QTcF Analysis | 0 Participants |
| Part 1a (SAD): ATH-399A 80 mg | QTcF Analysis | 1 Participants |
| Part 1a (SAD): Placebo | QTcF Analysis | 1 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | QTcF Analysis | 0 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | QTcF Analysis | 1 Participants |
| Part 2 (MAD): ATH-399A 20 mg | QTcF Analysis | 0 Participants |
| Part 2 (MAD): ATH-399A 40 mg | QTcF Analysis | 1 Participants |
| Part 2 (MAD): ATH-399A 40 mg, Older | QTcF Analysis | 2 Participants |
| Part 2 (MAD): Placebo | QTcF Analysis | 0 Participants |
Primary
Respiratory Rate Value
Respiratory rate value measured at Day 1, 1 Hour Post-Dose
Time frame: Day 1, 1 Hour Post-Dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Respiratory Rate Value | 14.7 breaths/min | Standard Deviation 2.73 |
| Part 1a (SAD): ATH-399A 10 mg | Respiratory Rate Value | 16.0 breaths/min | Standard Deviation 3.58 |
| Part 1a (SAD): ATH-399A 20 mg | Respiratory Rate Value | 13.7 breaths/min | Standard Deviation 1.51 |
| Part 1a (SAD): ATH-399A 40 mg | Respiratory Rate Value | 13.0 breaths/min | Standard Deviation 3.74 |
| Part 1a (SAD): ATH-399A 80 mg | Respiratory Rate Value | 14.3 breaths/min | Standard Deviation 2.34 |
| Part 1a (SAD): Placebo | Respiratory Rate Value | 13.0 breaths/min | Standard Deviation 3.3 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Respiratory Rate Value | 15.5 breaths/min | Standard Deviation 3.09 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Respiratory Rate Value | 14.3 breaths/min | Standard Deviation 1.98 |
| Part 2 (MAD): ATH-399A 20 mg | Respiratory Rate Value | 14.7 breaths/min | Standard Deviation 1.03 |
| Part 2 (MAD): ATH-399A 40 mg | Respiratory Rate Value | 15.0 breaths/min | Standard Deviation 1.1 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Respiratory Rate Value | 13.0 breaths/min | Standard Deviation 3.52 |
| Part 2 (MAD): Placebo | Respiratory Rate Value | 13.3 breaths/min | Standard Deviation 2.07 |
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 10 mg | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 20 mg | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 40 mg | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 1a (SAD): ATH-399A 80 mg | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 1a (SAD): Placebo | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 2 (MAD): ATH-399A 20 mg | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 2 (MAD): ATH-399A 40 mg | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 2 (MAD): ATH-399A 40 mg, Older | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
| Part 2 (MAD): Placebo | Serious TEAEs | 0 Serious Treatment Emergent Adverse Event |
Primary
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)
Population: Participants in each part were combined for reporting results given there were 0 reports across the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 1a (SAD): ATH-399A 10 mg | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 1a (SAD): ATH-399A 20 mg | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 1a (SAD): ATH-399A 40 mg | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 1a (SAD): ATH-399A 80 mg | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 1a (SAD): Placebo | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 2 (MAD): ATH-399A 20 mg | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 2 (MAD): ATH-399A 40 mg | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 2 (MAD): ATH-399A 40 mg, Older | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
| Part 2 (MAD): Placebo | Suicidal Ideation and/or Behavior Detected in Columbia Suicidality Severity Rating Scale (C-SSRS) | 0 Participants |
Primary
Temperature Value
Temperature value measured at Day 1, 1 Hour Post-Dose
Time frame: Day 1, 1 Hour Post-Dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Temperature Value | 36.63 °C | Standard Deviation 0.103 |
| Part 1a (SAD): ATH-399A 10 mg | Temperature Value | 36.67 °C | Standard Deviation 0.121 |
| Part 1a (SAD): ATH-399A 20 mg | Temperature Value | 36.72 °C | Standard Deviation 0.232 |
| Part 1a (SAD): ATH-399A 40 mg | Temperature Value | 36.78 °C | Standard Deviation 0.147 |
| Part 1a (SAD): ATH-399A 80 mg | Temperature Value | 36.73 °C | Standard Deviation 0.216 |
| Part 1a (SAD): Placebo | Temperature Value | 36.78 °C | Standard Deviation 0.21 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Temperature Value | 36.80 °C | Standard Deviation 0.16 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Temperature Value | 36.73 °C | Standard Deviation 0.116 |
| Part 2 (MAD): ATH-399A 20 mg | Temperature Value | 36.93 °C | Standard Deviation 0.151 |
| Part 2 (MAD): ATH-399A 40 mg | Temperature Value | 36.58 °C | Standard Deviation 0.117 |
| Part 2 (MAD): ATH-399A 40 mg, Older | Temperature Value | 36.63 °C | Standard Deviation 0.207 |
| Part 2 (MAD): Placebo | Temperature Value | 36.70 °C | Standard Deviation 0.167 |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | AUC0-inf | 45.92 h*ng/mL | Standard Deviation 9.28 |
| Part 1a (SAD): ATH-399A 10 mg | AUC0-inf | 86.22 h*ng/mL | Standard Deviation 32.59 |
| Part 1a (SAD): ATH-399A 20 mg | AUC0-inf | 212.02 h*ng/mL | Standard Deviation 95.27 |
| Part 1a (SAD): ATH-399A 40 mg | AUC0-inf | 522.19 h*ng/mL | Standard Deviation 172.75 |
| Part 1a (SAD): ATH-399A 80 mg | AUC0-inf | 1200.69 h*ng/mL | Standard Deviation 320.04 |
| Part 1a (SAD): Placebo | AUC0-inf | 720.93 h*ng/mL | Standard Deviation 211.31 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | AUC0-inf | 625.05 h*ng/mL | Standard Deviation 209.54 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | AUC0-inf | 485.14 h*ng/mL | Standard Deviation 134 |
| Part 2 (MAD): ATH-399A 20 mg | AUC0-inf | 1454.58 h*ng/mL | Standard Deviation 629.97 |
| Part 2 (MAD): ATH-399A 40 mg | AUC0-inf | 1782.88 h*ng/mL | Standard Deviation 504.1 |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | AUC0-t | 34.19 h*ng/mL | Standard Deviation 8.34 |
| Part 1a (SAD): ATH-399A 10 mg | AUC0-t | 53.71 h*ng/mL | Standard Deviation 30.15 |
| Part 1a (SAD): ATH-399A 20 mg | AUC0-t | 168.62 h*ng/mL | Standard Deviation 73.85 |
| Part 1a (SAD): ATH-399A 40 mg | AUC0-t | 481.81 h*ng/mL | Standard Deviation 171.08 |
| Part 1a (SAD): ATH-399A 80 mg | AUC0-t | 1093.98 h*ng/mL | Standard Deviation 274.05 |
| Part 1a (SAD): Placebo | AUC0-t | 651.13 h*ng/mL | Standard Deviation 179.31 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | AUC0-t | 569.69 h*ng/mL | Standard Deviation 189.58 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | AUC0-t | 450.52 h*ng/mL | Standard Deviation 124.54 |
| Part 2 (MAD): ATH-399A 20 mg | AUC0-t | 1337.49 h*ng/mL | Standard Deviation 577.26 |
| Part 2 (MAD): ATH-399A 40 mg | AUC0-t | 1601.07 h*ng/mL | Standard Deviation 476.59 |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | AUC0-t on Day 1 Dose for Part 2 | 83.99 h*ng/mL | Standard Deviation 34.09 |
| Part 1a (SAD): ATH-399A 10 mg | AUC0-t on Day 1 Dose for Part 2 | 208.14 h*ng/mL | Standard Deviation 126 |
| Part 1a (SAD): ATH-399A 20 mg | AUC0-t on Day 1 Dose for Part 2 | 186.80 h*ng/mL | Standard Deviation 88.77 |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | AUC0-τ (AUC0-24 at Day 12 Dose) for Part 2 | 251.24 h*ng/mL | Standard Deviation 81.96 |
| Part 1a (SAD): ATH-399A 10 mg | AUC0-τ (AUC0-24 at Day 12 Dose) for Part 2 | 725.06 h*ng/mL | Standard Deviation 345.98 |
| Part 1a (SAD): ATH-399A 20 mg | AUC0-τ (AUC0-24 at Day 12 Dose) for Part 2 | 774.81 h*ng/mL | Standard Deviation 298.05 |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Cavg | 10.47 ng/mL | Standard Deviation 3.41 |
| Part 1a (SAD): ATH-399A 10 mg | Cavg | 30.21 ng/mL | Standard Deviation 14.42 |
| Part 1a (SAD): ATH-399A 20 mg | Cavg | 32.28 ng/mL | Standard Deviation 12.42 |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Cmax | 1.53 ng/mL | Standard Deviation 0.55 |
| Part 1a (SAD): ATH-399A 10 mg | Cmax | 1.93 ng/mL | Standard Deviation 1.03 |
| Part 1a (SAD): ATH-399A 20 mg | Cmax | 9.11 ng/mL | Standard Deviation 5.28 |
| Part 1a (SAD): ATH-399A 40 mg | Cmax | 20.57 ng/mL | Standard Deviation 11.95 |
| Part 1a (SAD): ATH-399A 80 mg | Cmax | 45.40 ng/mL | Standard Deviation 14.51 |
| Part 1a (SAD): Placebo | Cmax | 22.50 ng/mL | Standard Deviation 7.9 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Cmax | 22.49 ng/mL | Standard Deviation 11.58 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Cmax | 5.32 ng/mL | Standard Deviation 2.46 |
| Part 2 (MAD): ATH-399A 20 mg | Cmax | 14.21 ng/mL | Standard Deviation 10.64 |
| Part 2 (MAD): ATH-399A 40 mg | Cmax | 13.78 ng/mL | Standard Deviation 10.23 |
Secondary
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.
Population: Cmax ss has been analyzed only in patients included in Part 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Cmax, ss | 14.98 ng/mL | Standard Deviation 6.89 |
| Part 1a (SAD): ATH-399A 10 mg | Cmax, ss | 51.88 ng/mL | Standard Deviation 34.86 |
| Part 1a (SAD): ATH-399A 20 mg | Cmax, ss | 46.04 ng/mL | Standard Deviation 21.52 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Cmin ss | 6.25 ng/mL | Standard Deviation 2.16 |
| Part 1a (SAD): ATH-399A 10 mg | Cmin ss | 17.91 ng/mL | Standard Deviation 6.87 |
| Part 1a (SAD): ATH-399A 20 mg | Cmin ss | 20.39 ng/mL | Standard Deviation 6.89 |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | t½ el | 23.86 hours | Standard Deviation 4.8 |
| Part 1a (SAD): ATH-399A 10 mg | t½ el | 23.32 hours | Standard Deviation 4.96 |
| Part 1a (SAD): ATH-399A 20 mg | t½ el | 19.71 hours | Standard Deviation 4.01 |
| Part 1a (SAD): ATH-399A 40 mg | t½ el | 26.77 hours | Standard Deviation 5.59 |
| Part 1a (SAD): ATH-399A 80 mg | t½ el | 28.31 hours | Standard Deviation 4.65 |
| Part 1a (SAD): Placebo | t½ el | 28.48 hours | Standard Deviation 5.62 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | t½ el | 27.32 hours | Standard Deviation 4.82 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | t½ el | 24.63 hours | Standard Deviation 3.28 |
| Part 2 (MAD): ATH-399A 20 mg | t½ el | 26.44 hours | Standard Deviation 2.59 |
| Part 2 (MAD): ATH-399A 40 mg | t½ el | 29.85 hours | Standard Deviation 3.44 |
Secondary
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Tmax | 7 hours |
| Part 1a (SAD): ATH-399A 10 mg | Tmax | 8.009 hours |
| Part 1a (SAD): ATH-399A 20 mg | Tmax | 4.500 hours |
| Part 1a (SAD): ATH-399A 40 mg | Tmax | 4.059 hours |
| Part 1a (SAD): ATH-399A 80 mg | Tmax | 7 hours |
| Part 1a (SAD): Placebo | Tmax | 6.009 hours |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | Tmax | 4 hours |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | Tmax | 5.009 hours |
| Part 2 (MAD): ATH-399A 20 mg | Tmax | 7 hours |
| Part 2 (MAD): ATH-399A 40 mg | Tmax | 8.017 hours |
Secondary
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | Tmax, ss | 5 hours |
| Part 1a (SAD): ATH-399A 10 mg | Tmax, ss | 4 hours |
| Part 1a (SAD): ATH-399A 20 mg | Tmax, ss | 5.5 hours |
Secondary
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1a (SAD): ATH-399A 5 mg | λz | 0.0304 1/hr | Standard Deviation 0.0081 |
| Part 1a (SAD): ATH-399A 10 mg | λz | 0.0308 1/hr | Standard Deviation 0.0062 |
| Part 1a (SAD): ATH-399A 20 mg | λz | 0.0363 1/hr | Standard Deviation 0.0069 |
| Part 1a (SAD): ATH-399A 40 mg | λz | 0.0269 1/hr | Standard Deviation 0.0057 |
| Part 1a (SAD): ATH-399A 80 mg | λz | 0.0250 1/hr | Standard Deviation 0.0041 |
| Part 1a (SAD): Placebo | λz | 0.0253 1/hr | Standard Deviation 0.0052 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fed | λz | 0.0261 1/hr | Standard Deviation 0.0047 |
| Part 1b (Food Effect): ATH-399A 40 mg, Fasted | λz | 0.0286 1/hr | Standard Deviation 0.0041 |
| Part 2 (MAD): ATH-399A 20 mg | λz | 0.0264 1/hr | Standard Deviation 0.0026 |
| Part 2 (MAD): ATH-399A 40 mg | λz | 0.0235 1/hr | Standard Deviation 0.0028 |