Parkinson's Disease
Conditions
Keywords
FAF1, Fas (TNFRSF6)-associated factor 1, FAF1 inhibitor, KM-819
Brief summary
This first in human, single-center, randomized, placebo-controlled, double blind, sequential group Phase 1 study in healthy subjects will be conducted to evaluate the safety, tolerability, PK, and PD following the escalation of single and multiple doses of KM-819. The study will consist of 2 parts. In Part A, up to 5 cohorts of young adult male subjects, and 1 single dose cohort of elderly male or post menopausal female subjects will receive escalating single doses of KM-819. In Part B, up to 4 cohorts of healthy young adult male subjects and 1 multiple dose cohort of elderly male or post menopausal female subjects will receive escalating multiple doses of KM-819. Part B will be conducted after completion of all cohorts of young adult male subjects in Part A. Dose escalation to the next level will be determined using safety, tolerability, and PK data of the previous cohort. Part A, Single Ascending Dose (SAD) Up to 40 healthy young adult male subjects and 8 healthy elderly male or post menopausal female subjects will be enrolled and randomized to receive either KM-819 or placebo. Each of the 5 dose escalation cohorts consists of 8 healthy young adult male subjects; 6 subjects will receive 10, 30, 100, 200, or 400 mg of KM-819 and 2 subjects will receive placebo. In each single dose cohort, dosing of subjects will be sentinel, i.e., 2 subjects will be dosed on the first day (1 subject will receive active treatment and 1 subject will receive placebo) and the remaining 6 subjects will be dosed at least 24 hours after the first 2 subjects. Cohorts will be dosed sequentially with escalating doses. Eight elderly male or post-menopausal female subjects will be enrolled into an additional cohort; 6 subjects will receive 200 mg KM-819 and 2 subjects will receive placebo. Part A consists of a Screening period of up to 28 days, and a 3 day Confinement period when subjects are hospitalized for study activities. Subjects are required to return for outpatient visits on Day 4, 7 and for the Follow up Visit on Day 14. Part B, Multiple Ascending Dose (MAD) Up to 32 healthy young adult male subjects and 8 healthy elderly male or post menopausal female subjects will be enrolled and randomized to receive either KM-819 or placebo. Each of the 4 dose escalation cohorts consists of 8 healthy young adult male subjects; 6 subjects will receive 30, 100, 200, or 400 mg of KM-819 once a day (QD) for 7 days and 2 subjects will receive placebo. Cohorts will be dosed sequentially with escalating doses. Eight elderly male or post-menopausal female subjects will be enrolled into an additional cohort; 6 subjects will receive 200 mg KM-819 QD for 7 days and 2 subjects will receive placebo.
Interventions
DRUGKM-819
DRUGPlacebo
Sponsors
Kainos Medicine Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Male subject should be 19 to 45 years old (for young adult cohorts) or over 60 years old (for elderly cohorts). 3. Subject has a body mass index (BMI) range of 18.5 to 30 kg/m2 inclusive at Screening. 4. Male subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening and continuing throughout the study period and for 90 days after final study drug administration. Highly effective contraception is defined as: * Established use of oral, injected, or implanted hormonal methods of contraception * Placement of an intrauterine device or intrauterine system * Barrier methods of contraception: condom with spermicidal foam, gel, film, cream, suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream, or suppository 5. Male subject must not donate sperm starting at Screening, throughout the study period and for at least 90 days after final study drug administration. 6. Female subject must be over 60 years old and post-menopausal (defined as at least 1 year without any menses) prior to Screening. 7. Subject agrees not to participate in another investigational study while on study treatment.
Exclusion criteria
1. Subject has a known or suspected hypersensitivity to KM-819, or any components of the formulation(s) used. 2. Subject has previously participated in a clinical study with KM-819. 3. Subject has any of the liver enzymes (aspartate aminotransferase \[AST\], alanine transaminase \[ALT\], alkaline phosphatase, γ glutamyl transferase) or total bilirubin (TBIL) above the ULN. If any liver enzyme is \> 1 × ULN but \< 1.5 × ULN, the assessment may be repeated once during the Screening period or on check-in. If the repeated assessment is above the ULN, it is exclusionary. If the initial value is \> 1.5 × ULN, it cannot be repeated and is exclusionary. 4. Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, allergic rhinitis or rhino-conjunctivitis, or house dust mite allergy at time of dosing). 5. Subject with a history of a suicide attempt or suicidal behavior. Any recent suicidal ideation (a level of 4 or 5) within the last 3 months, or having a positive C-SSRS at check-in (Day -1), or who is at significant risk to commit suicide, as judged by the Investigator using the C SSRS at Screening. 6. Subject has/had febrile illness or symptomatic viral, bacterial (including upper respiratory infection) or fungal (non-cutaneous) infection within 1 week before site check-in. 7. Subject has any clinically significant abnormality following the Investigator's review of the physical examination, ECG, and protocol-defined clinical laboratory tests at Screening or site check-in. 8. Subject has a mean pulse \< 40 or \> 90 beats per minute (bpm); mean systolic blood pressure (SBP) \> 140 mmHg; or mean diastolic blood pressure (DBP) \> 90 mmHg (measurements taken in triplicate after subject has been resting in the supine position for 5 minutes; pulse will be measured automatically) at Screening or check-in. If the mean pulse, mean SBP, or mean DBP is out of the range specified above, 1 additional triplicate measurement may be taken at Screening and check-in. 9. Subject has a mean QTcF interval of \> 430 msec (for males) and \> 450 msec (for females) at Screening or check-in. If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken. If this triplicate also gives an abnormal result, the subject should be excluded. 10. Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsade de pointes, structural heart disease, or a family history of Long QT Syndrome. 11. Subject has use of any prescribed or non-prescribed drugs (including vitamins, hormone replacement therapy, natural and herbal remedies, e.g., St. John's Wort) in the 2 weeks before study drug administration. Acetaminophen up to 2000 mg/day is allowed. 12. Subject has had any use of tobacco- or nicotine-containing products within 6 months prior to Screening. 13. Subject has history of consuming more than 14 units of alcoholic beverages per week within 6 months prior to Screening or has a history of alcoholism or abuse of amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates (drugs-of-abuse) within the past 2 years prior to Screening (Note: 1 unit = 355 mL of beer, 118 mL of wine, or 29 mL of spirits/hard liquor) or the subject tests positive at Screening or site admission for alcohol or drugs of-abuse. 14. Subject has used any drugs-of-abuse within 3 months before check in. 15. Subject has used any inducers of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to check-in. 16. Subject has any significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood, or blood products within 60 days or donated plasma within 7 days before check-in. 17. Subject has a positive serology test for hepatitis B surface antigen (HbsAg), anti hepatitis A virus Immunoglobulin M (HAV IgM), anti-hepatitis C virus (HCV Ab), or anti-human immunodeficiency virus (HIV Ab). 18. Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 3 months or 5 half lives, whichever is longer, before the initiation of Screening. 19. Subject has (recent history of) any other condition which, in the opinion of the Investigator, precludes the subject's participation in the trial. 20. Subject is an employee of the Kainos Medicine, Inc. or vendors involved in the study. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From screening (Day-28 to Day -2), Day -1 to Day 4, Day 7, and follow-up visit Day 14. | All AEs will be coded using the latest available version 19.1 of the Medical Dictionary for Regulatory Activities (MedDRA). A treatment-emergent adverse event (TEAE) is defined as an AE that begins or that worsens in severity after at least one dose of the study drug has been administered. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A:Day 1 to 4; Part B: Day 1 to Day 8 | To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| t½ (Apparent Terminal Elimination Half Life) | Part A: Day 1 to Day 4. Part B: Day1 to Day 8 | To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects. To evaluate the PK and PD of single and multiple oral doses of KM-819 in elderly male subjects. |
| Tlag (Lag Time) | Part A: Day1 to Day 4. Part B: Day 1 to Day 8 | To evaluate the T lag of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part A: Day 1 to 4; Part B: Day 1 to Day 8 | To evaluate AUClast of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part A: Day 1 to 4; Part B: Day 1 to Day 8 | To evaluate AUCinf of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male-subjects. |
| %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part A: Day 1 to 4; Part B: Day 1 to Day 8 | To evaluate %AUCex of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| CL/F (Apparent Oral Clearance) | Part A: Day 1 to 4; Part B: Day 1 to Day 8 | To evaluate the CL/F of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| Vz/F (Apparent Volume of Distribution) | Part A: Day 1 to 4; Part B: Day 1 to Day 8 | To evaluate Vz/F of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects. |
| AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B) | Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, | To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects. |
| Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A: Day1 to Day 4. Part B: Day-1 to Day 8 | To evaluate Cmax of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| Rac (Cmax) (Observed Accumulation by Cmax) (Part B) | Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, | To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| AUCtau_D (AUCtau Divided by Dose) (Part B) | Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, | To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | At Day 1 (3 hours post dose), Day2, Day 3, Day 4, and Day 8. | The Bond-Lader Visual Analogue Scales (VAS) will be analyzed using 3 factor scores: alertness, contentedness, and calmness. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered. Baseline is defined as the last available recording prior to dosing on Day 1. 1. Alertness (Range 0 to 100, the higher scores indicated more alertness) 2. Mood (Range 0 to 100, where higher scores indicated elevated mood) 3. Calmness (Range 0 to 100, where higher scores indicated more calmness). |
| Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Part A: Day 1; Part B: Day 7 | The K-WAIS-IV consists of an assessment of the cognitive ability using a core battery of 10 unique subtests (Block Design, Similarities, Digit Span, Matrix Reasoning, Vocabulary, Arithmetic, Symbol Search, Visual Puzzles, Information, and Coding) that focus on four specific domains of intelligence: verbal comprehension, perceptual reasoning, working memory, and processing speed. The Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index (standard scores: mean=100, standard deviation=15) that are all based on a number of core and supplemental subtests (scaled scores: mean=15, standard deviation=3) that provide pertinent clinical information and flexibility in implementation. The higher values represent a better outcome. |
| Alpha Synuclein Oligomer in Plasma and CSF (Part B) | Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: Day 7 (at 1 hour after last dosing) | To evaluate Alpha synuclein oligomer in plasma and CSF of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| Change From Baseline Total Tau in CSF (Part B) | CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing) | To evaluate Total Tau in CSF of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| Change From Baseline Phospho-Tau in CSF (Part B) | CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing) | To evaluate Phospho-Tau of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects. |
| Ratio of CSF Concentration/Plasma Cmax (Part B) | Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: on Day 7 (at 1 hour after last dosing) | Ratio of CSF concentration/Plasma Cmax |
| Rac(AUC) (Observed Accumulation by AUC) (Part B) | Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, | To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects. |
Countries
South Korea
Participant flow
Recruitment details
A first in human, single center, randomized, placebo controlled, double blind, sequential group Phase 1 study in healthy subjects recruited from Nov 2016 to Sep 2017. Participants who met all the inclusion and none of the exclusion criteria were enrolled.
Pre-assignment details
All subjects underwent a Screening period of up to 28 days and a 3 day Confinement period when they were hospitalized for study activities (Day -1 to Day 3) for Part A (Single Ascending Doses) and an 8 day Confinement period when they were hospitalized for study activities (Day -1 to Day 8) for Part B (Multiple Ascending Doses)
Participants by arm
| Arm | Count |
|---|---|
| KM-819 - 10 mg (Part A) 6 subjects in this cohort received 10 mg of KM-819 orally with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 - 30 mg (Part A) 6 subjects in this cohort received 30 mg of KM-819 orally with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 - 100mg (Part A) 6 subjects in this cohort received 100 mg of KM-819 orally with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 200mg (Part A) 6 subjects in this cohort received 200 mg of KM-819 orally with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 - 400mg (Part A) 6 subjects in this cohort received 400 mg of KM-819 orally with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 200mg (Elderly Male Subjects) (Part A) 6 elderly male subjects in this cohort received 200 mg of KM-819 orally with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| Placebo (Part A) 12 subjects received placebo orally with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 12 |
| KM-819 30 mg (Part B) 6 subjects in this cohort received 30 mg of KM-819 orally on Day 2 to Day 6, the study drug was administered with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 100 mg (Part B) 6 subjects in this cohort received 100 mg of KM-819 orally on Day 2 to Day 6, the study drug was administered with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 200mg (Part B) 6 subjects in this cohort received 200 mg of KM-819 orally on Day 2 to Day 6, the study drug was administered with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 400mg (Part B) 6 subjects in this cohort received 400 mg of KM-819 orally on Day 2 to Day 6, the study drug was administered with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| KM-819 200mg (Elderly Male Subjects) (Part B) 6 elderly male subjects in this cohort received 30 mg of KM-819 orally on Day 2 to Day 6, the study drug was administered with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 6 |
| Placebo (Part B) 10 subjects received placebo of KM-819 orally on Day 2 to Day 6, the study drug was administered with approximately 240 mL of water (room temperature), after an overnight fasting for a minimum of 8 hours. | 10 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | KM-819 - 10 mg (Part A) | Total | Placebo (Part B) | KM-819 200mg (Elderly Male Subjects) (Part B) | KM-819 400mg (Part B) | KM-819 200mg (Part B) | KM-819 100 mg (Part B) | KM-819 30 mg (Part B) | Placebo (Part A) | KM-819 200mg (Elderly Male Subjects) (Part A) | KM-819 - 400mg (Part A) | KM-819 200mg (Part A) | KM-819 - 100mg (Part A) | KM-819 - 30 mg (Part A) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 23.7 Years STANDARD_DEVIATION 6.28 | 35.3 Years STANDARD_DEVIATION 7.8 | 38.5 Years STANDARD_DEVIATION 19.73 | 72.8 Years STANDARD_DEVIATION 6.59 | 22.5 Years STANDARD_DEVIATION 1.38 | 28.7 Years STANDARD_DEVIATION 5.65 | 30.2 Years STANDARD_DEVIATION 6.85 | 27.5 Years STANDARD_DEVIATION 7.56 | 35.6 Years STANDARD_DEVIATION 19.76 | 75.0 Years STANDARD_DEVIATION 5.76 | 26.3 Years STANDARD_DEVIATION 4.13 | 27.5 Years STANDARD_DEVIATION 6.38 | 26.2 Years STANDARD_DEVIATION 5.04 | 25.2 Years STANDARD_DEVIATION 7.57 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 87 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 11 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 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 | 0 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 | 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 | 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 | 0 Participants |
| Race (NIH/OMB) White | 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 | 0 Participants |
| Sex: Female, Male Female | 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 | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 88 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 12 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
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 | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 12 | 2 / 6 | 2 / 6 | 3 / 6 | 1 / 6 | 0 / 6 | 4 / 6 | 10 / 10 | 6 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events
All AEs will be coded using the latest available version 19.1 of the Medical Dictionary for Regulatory Activities (MedDRA). A treatment-emergent adverse event (TEAE) is defined as an AE that begins or that worsens in severity after at least one dose of the study drug has been administered.
Time frame: From screening (Day-28 to Day -2), Day -1 to Day 4, Day 7, and follow-up visit Day 14.
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| KM-819 - 10 mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 - 10 mg (Part A) | Number of Participants With Adverse Events | Related TEAEs | 2 participants |
| KM-819 - 10 mg (Part A) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 - 10 mg (Part A) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 - 10 mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 - 10 mg (Part A) | Number of Participants With Adverse Events | TEAEs | 2 participants |
| KM-819 - 30 mg (Part A) | Number of Participants With Adverse Events | Related TEAEs | 0 participants |
| KM-819 - 30 mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 - 30 mg (Part A) | Number of Participants With Adverse Events | TEAEs | 2 participants |
| KM-819 - 30 mg (Part A) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 - 30 mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 - 30 mg (Part A) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 - 100mg (Part A) | Number of Participants With Adverse Events | TEAEs | 2 participants |
| KM-819 - 100mg (Part A) | Number of Participants With Adverse Events | Related TEAEs | 1 participants |
| KM-819 - 100mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 - 100mg (Part A) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 - 100mg (Part A) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 - 100mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 200mg (Part A) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 200mg (Part A) | Number of Participants With Adverse Events | TEAEs | 1 participants |
| KM-819 200mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 200mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 200mg (Part A) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 200mg (Part A) | Number of Participants With Adverse Events | Related TEAEs | 1 participants |
| KM-819 - 400mg (Part A) | Number of Participants With Adverse Events | Related TEAEs | 0 participants |
| KM-819 - 400mg (Part A) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 - 400mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 - 400mg (Part A) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 - 400mg (Part A) | Number of Participants With Adverse Events | TEAEs | 0 participants |
| KM-819 - 400mg (Part A) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Number of Participants With Adverse Events | TEAEs | 2 participants |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Number of Participants With Adverse Events | Related TEAEs | 2 participants |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| Placebo (Part A) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| Placebo (Part A) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| Placebo (Part A) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| Placebo (Part A) | Number of Participants With Adverse Events | TEAEs | 3 participants |
| Placebo (Part A) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| Placebo (Part A) | Number of Participants With Adverse Events | Related TEAEs | 1 participants |
| KM-819 30 mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 30 mg (Part B) | Number of Participants With Adverse Events | Related TEAEs | 2 participants |
| KM-819 30 mg (Part B) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 30 mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 30 mg (Part B) | Number of Participants With Adverse Events | TEAEs | 2 participants |
| KM-819 30 mg (Part B) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 100 mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 100 mg (Part B) | Number of Participants With Adverse Events | TEAEs | 4 participants |
| KM-819 100 mg (Part B) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 100 mg (Part B) | Number of Participants With Adverse Events | Related TEAEs | 2 participants |
| KM-819 100 mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 100 mg (Part B) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 200mg (Part B) | Number of Participants With Adverse Events | Related TEAEs | 5 participants |
| KM-819 200mg (Part B) | Number of Participants With Adverse Events | Serious TEAEs | 1 participants |
| KM-819 200mg (Part B) | Number of Participants With Adverse Events | Severe TEAEs | 1 participants |
| KM-819 200mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 200mg (Part B) | Number of Participants With Adverse Events | TEAEs | 5 participants |
| KM-819 200mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 1 participants |
| KM-819 400mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 1 participants |
| KM-819 400mg (Part B) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 400mg (Part B) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 400mg (Part B) | Number of Participants With Adverse Events | Related TEAEs | 4 participants |
| KM-819 400mg (Part B) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| KM-819 400mg (Part B) | Number of Participants With Adverse Events | TEAEs | 5 participants |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Number of Participants With Adverse Events | TEAEs | 3 participants |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Number of Participants With Adverse Events | Related TEAEs | 3 participants |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
| Placebo (Part B) | Number of Participants With Adverse Events | Related TEAEs | 5 participants |
| Placebo (Part B) | Number of Participants With Adverse Events | TEAEs leading to death | 0 participants |
| Placebo (Part B) | Number of Participants With Adverse Events | TEAEs | 5 participants |
| Placebo (Part B) | Number of Participants With Adverse Events | TEAEs leading to withdrawal | 0 participants |
| Placebo (Part B) | Number of Participants With Adverse Events | Serious TEAEs | 0 participants |
| Placebo (Part B) | Number of Participants With Adverse Events | Severe TEAEs | 0 participants |
Secondary
Alpha Synuclein Oligomer in Plasma and CSF (Part B)
To evaluate Alpha synuclein oligomer in plasma and CSF of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: Day 7 (at 1 hour after last dosing)
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| KM-819 - 10 mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | CSF, Day 7, 1 hour postdose | 49.9424 pg/mL |
| KM-819 - 10 mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | Plasma, Day 7, 1 hour postdose | 3884.4127 pg/mL |
| KM-819 - 30 mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | CSF, Day 7, 1 hour postdose | -252.5578 pg/mL |
| KM-819 - 30 mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | Plasma, Day 7, 1 hour postdose | 575.4570 pg/mL |
| KM-819 - 100mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | CSF, Day 7, 1 hour postdose | 0.6012 pg/mL |
| KM-819 - 100mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | Plasma, Day 7, 1 hour postdose | 3809.5090 pg/mL |
| KM-819 200mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | CSF, Day 7, 1 hour postdose | 18.2112 pg/mL |
| KM-819 200mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | Plasma, Day 7, 1 hour postdose | -64843.287 pg/mL |
| KM-819 - 400mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | CSF, Day 7, 1 hour postdose | 34.8672 pg/mL |
| KM-819 - 400mg (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | Plasma, Day 7, 1 hour postdose | -11712.090 pg/mL |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | CSF, Day 7, 1 hour postdose | 20.3025 pg/mL |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Alpha Synuclein Oligomer in Plasma and CSF (Part B) | Plasma, Day 7, 1 hour postdose | -4464.9082 pg/mL |
Secondary
%AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast)
To evaluate %AUCex of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part A | 1.664 percentage of AUC | Geometric Coefficient of Variation 50.5 |
| KM-819 - 30 mg (Part A) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part A | 1.331 percentage of AUC | Geometric Coefficient of Variation 51.2 |
| KM-819 - 100mg (Part A) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part A | 1.338 percentage of AUC | Geometric Coefficient of Variation 19 |
| KM-819 200mg (Part A) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part A | 0.7787 percentage of AUC | Geometric Coefficient of Variation 65.4 |
| KM-819 - 400mg (Part A) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part A | 0.4833 percentage of AUC | Geometric Coefficient of Variation 164.4 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part A | 0.9795 percentage of AUC | Geometric Coefficient of Variation 77.9 |
| Placebo (Part A) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part B | 1.273 percentage of AUC | Geometric Coefficient of Variation 43.9 |
| KM-819 30 mg (Part B) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part B | 3.075 percentage of AUC | Geometric Coefficient of Variation 63.3 |
| KM-819 100 mg (Part B) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part B | 2.263 percentage of AUC | Geometric Coefficient of Variation 84.8 |
| KM-819 400mg (Part B) | %AUCex (Percentage of AUCinf That is Due to Extrapolation Beyond Tlast) | Part B | 1.982 percentage of AUC | Geometric Coefficient of Variation 112.1 |
Secondary
AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity)
To evaluate AUCinf of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male-subjects.
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part A | 594.2 h*ng/mL | Geometric Coefficient of Variation 24.4 |
| KM-819 - 30 mg (Part A) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part A | 1731 h*ng/mL | Geometric Coefficient of Variation 17.3 |
| KM-819 - 100mg (Part A) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part A | 4872 h*ng/mL | Geometric Coefficient of Variation 30.8 |
| KM-819 200mg (Part A) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part A | 7338 h*ng/mL | Geometric Coefficient of Variation 51.9 |
| KM-819 - 400mg (Part A) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part A | 12640 h*ng/mL | Geometric Coefficient of Variation 36.1 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part A | 10970 h*ng/mL | Geometric Coefficient of Variation 9.8 |
| Placebo (Part A) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part B-Day 1 | 1713 h*ng/mL | Geometric Coefficient of Variation 22.4 |
| KM-819 30 mg (Part B) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part B-Day 1 | 3884 h*ng/mL | Geometric Coefficient of Variation 41.5 |
| KM-819 100 mg (Part B) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part B-Day 1 | 10070 h*ng/mL | Geometric Coefficient of Variation 30.8 |
| KM-819 400mg (Part B) | AUCinf (Area Under the Plasma Concentration-time Curve From Predose (Time 0) Extrapolated to Infinity) | Part B-Day 1 | 18550 h*ng/mL | Geometric Coefficient of Variation 57.8 |
Secondary
AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration)
To evaluate AUClast of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part A | 597.5 h*ng/mL | Standard Deviation 140.5 |
| KM-819 - 30 mg (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part A | 1726 h*ng/mL | Standard Deviation 289.7 |
| KM-819 - 100mg (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part A | 4479 h*ng/mL | Standard Deviation 1423 |
| KM-819 200mg (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part A | 8210 h*ng/mL | Standard Deviation 2912 |
| KM-819 - 400mg (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part A | 12770 h*ng/mL | Standard Deviation 4321 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part A | 10880 h*ng/mL | Standard Deviation 1108 |
| Placebo (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 7 | 1608 h*ng/mL | Standard Deviation 414.2 |
| Placebo (Part A) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 1 | 1786 h*ng/mL | Standard Deviation 379.4 |
| KM-819 30 mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 1 | 3944 h*ng/mL | Standard Deviation 1453 |
| KM-819 30 mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 7 | 3688 h*ng/mL | Standard Deviation 686 |
| KM-819 100 mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 1 | 7340 h*ng/mL | Standard Deviation 3890 |
| KM-819 100 mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 7 | 6333 h*ng/mL | Standard Deviation 2402 |
| KM-819 200mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 1 | 11880 h*ng/mL | Standard Deviation 4525 |
| KM-819 200mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 7 | 17330 h*ng/mL | Standard Deviation 10900 |
| KM-819 400mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 7 | 17020 h*ng/mL | Standard Deviation 5676 |
| KM-819 400mg (Part B) | AUClast (Area Under the Plasma Concentration-time From Predose (Time 0) to the Last Quantifiable Concentration) | Part B-Day 1 | 19660 h*ng/mL | Standard Deviation 11160 |
Secondary
AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Value (MEAN) |
|---|---|---|
| KM-819 - 10 mg (Part A) | AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B) | 1612 h*ng/mL |
| KM-819 - 30 mg (Part A) | AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B) | 3521 h*ng/mL |
| KM-819 - 100mg (Part A) | AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B) | 8039 h*ng/mL |
| KM-819 200mg (Part A) | AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B) | 22830 h*ng/mL |
| KM-819 - 400mg (Part A) | AUCtau (Area Under the Plasma Concentration-time Curve for a Dosing Interval) (Part B) | 17020 h*ng/mL |
Secondary
AUCtau_D (AUCtau Divided by Dose) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Value (MEAN) |
|---|---|---|
| KM-819 - 10 mg (Part A) | AUCtau_D (AUCtau Divided by Dose) (Part B) | 53.74 (h*ng/mL)/mg |
| KM-819 - 30 mg (Part A) | AUCtau_D (AUCtau Divided by Dose) (Part B) | 35.21 (h*ng/mL)/mg |
| KM-819 - 100mg (Part A) | AUCtau_D (AUCtau Divided by Dose) (Part B) | 40.19 (h*ng/mL)/mg |
| KM-819 200mg (Part A) | AUCtau_D (AUCtau Divided by Dose) (Part B) | 57.08 (h*ng/mL)/mg |
| KM-819 - 400mg (Part A) | AUCtau_D (AUCtau Divided by Dose) (Part B) | 85.09 (h*ng/mL)/mg |
Secondary
Change From Baseline for Bond and Lader Visual Analogue Scale (VAS)
The Bond-Lader Visual Analogue Scales (VAS) will be analyzed using 3 factor scores: alertness, contentedness, and calmness. Participants were asked to indicate on the VAS scale ranging from 0 to 100 mm about how they felt at the moment the scale was administered. Baseline is defined as the last available recording prior to dosing on Day 1. 1. Alertness (Range 0 to 100, the higher scores indicated more alertness) 2. Mood (Range 0 to 100, where higher scores indicated elevated mood) 3. Calmness (Range 0 to 100, where higher scores indicated more calmness).
Time frame: At Day 1 (3 hours post dose), Day2, Day 3, Day 4, and Day 8.
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 3, 48 hours postdose | -5.42 units on a scale | Standard Deviation 10.542 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 3, 48 hours postdose | -7.37 units on a scale | Standard Deviation 13.125 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -3.202 units on a scale | Standard Deviation 5.4359 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -7.13 units on a scale | Standard Deviation 12.139 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | -1.42 units on a scale | Standard Deviation 9.952 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | -0.482 units on a scale | Standard Deviation 3.6349 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | 0.42 units on a scale | Standard Deviation 8.417 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 4, 72 hours postdose | -7.00 units on a scale | Standard Deviation 11.021 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 4, 72 hours postdose | -6.665 units on a scale | Standard Deviation 5.8359 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 3, 48 hours postdose | -4.500 units on a scale | Standard Deviation 6.2535 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 4, 72 hours postdose | -3.42 units on a scale | Standard Deviation 11.16 |
| KM-819 - 10 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -1.83 units on a scale | Standard Deviation 6.77 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 4, 72 hours postdose | -0.80 units on a scale | Standard Deviation 2.086 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | 1.00 units on a scale | Standard Deviation 9.29 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | -4.315 units on a scale | Standard Deviation 8.8671 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 3, 48 hours postdose | -2.83 units on a scale | Standard Deviation 5.159 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | 1.30 units on a scale | Standard Deviation 5.383 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -0.465 units on a scale | Standard Deviation 11.1985 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -2.67 units on a scale | Standard Deviation 3.355 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 4, 72 hours postdose | 3.33 units on a scale | Standard Deviation 10.567 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 3, 48 hours postdose | -2.278 units on a scale | Standard Deviation 11.911 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 4, 72 hours postdose | -3.372 units on a scale | Standard Deviation 8.8024 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 3, 48 hours postdose | 0.42 units on a scale | Standard Deviation 7.651 |
| KM-819 - 30 mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | -3.08 units on a scale | Standard Deviation 6.888 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -2.37 units on a scale | Standard Deviation 3.194 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 3, 48 hours postdose | -3.80 units on a scale | Standard Deviation 5.374 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 4, 72 hours postdose | -8.50 units on a scale | Standard Deviation 11.908 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | -3.75 units on a scale | Standard Deviation 13.08 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 3, 48 hours postdose | -8.073 units on a scale | Standard Deviation 8.6618 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 3, 48 hours postdose | -9.92 units on a scale | Standard Deviation 9.388 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | 1.75 units on a scale | Standard Deviation 9.832 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 4, 72 hours postdose | -6.352 units on a scale | Standard Deviation 11.6716 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -3.53 units on a scale | Standard Deviation 3.384 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | 0.720 units on a scale | Standard Deviation 7.2589 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -2.333 units on a scale | Standard Deviation 3.4326 |
| KM-819 - 100mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 4, 72 hours postdose | -3.13 units on a scale | Standard Deviation 8.256 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -1.33 units on a scale | Standard Deviation 1.473 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | -1.17 units on a scale | Standard Deviation 9.852 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | -3.610 units on a scale | Standard Deviation 9.4171 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 4, 72 hours postdose | 1.42 units on a scale | Standard Deviation 7.807 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | 1.03 units on a scale | Standard Deviation 3.674 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -0.148 units on a scale | Standard Deviation 7.5707 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 3, 48 hours postdose | -1.07 units on a scale | Standard Deviation 3.84 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 4, 72 hours postdose | -3.23 units on a scale | Standard Deviation 3.024 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | 3.42 units on a scale | Standard Deviation 12.064 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 4, 72 hours postdose | -6.372 units on a scale | Standard Deviation 6.0623 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 3, 48 hours postdose | -3.128 units on a scale | Standard Deviation 6.5867 |
| KM-819 200mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 3, 48 hours postdose | -2.33 units on a scale | Standard Deviation 4.502 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 3, 48 hours postdose | -4.110 units on a scale | Standard Deviation 8.6208 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | -2.333 units on a scale | Standard Deviation 6.42 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -2.427 units on a scale | Standard Deviation 5.7016 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 4, 72 hours postdose | -3.368 units on a scale | Standard Deviation 9.2123 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | 0.25 units on a scale | Standard Deviation 4.709 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | 3.92 units on a scale | Standard Deviation 3.513 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 3, 48 hours postdose | 3.58 units on a scale | Standard Deviation 4.188 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 4, 72 hours postdose | 6.58 units on a scale | Standard Deviation 7.249 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -1.93 units on a scale | Standard Deviation 6.822 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -0.73 units on a scale | Standard Deviation 8.911 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 3, 48 hours postdose | -1.30 units on a scale | Standard Deviation 6.549 |
| KM-819 - 400mg (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 4, 72 hours postdose | -3.93 units on a scale | Standard Deviation 5.504 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | 2.315 units on a scale | Standard Deviation 4.8479 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 3, 48 hours postdose | 1.00 units on a scale | Standard Deviation 5.138 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | 3.093 units on a scale | Standard Deviation 3.7733 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 4, 72 hours postdose | -1.60 units on a scale | Standard Deviation 7.201 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | 0.83 units on a scale | Standard Deviation 8.43 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -3.10 units on a scale | Standard Deviation 13.121 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 3, 48 hours postdose | 0.37 units on a scale | Standard Deviation 7.337 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 4, 72 hours postdose | 0.42 units on a scale | Standard Deviation 4.443 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | 1.67 units on a scale | Standard Deviation 5.279 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 4, 72 hours postdose | 3.222 units on a scale | Standard Deviation 3.4213 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -0.53 units on a scale | Standard Deviation 9.226 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 3, 48 hours postdose | 5.500 units on a scale | Standard Deviation 5.2313 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | -2.926 units on a scale | Standard Deviation 11.4835 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -1.43 units on a scale | Standard Deviation 5.775 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | -1.04 units on a scale | Standard Deviation 6.58 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 3, 48 hours postdose | -4.572 units on a scale | Standard Deviation 9.7416 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 3, 48 hours postdose | -3.21 units on a scale | Standard Deviation 10.31 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 4, 72 hours postdose | -7.814 units on a scale | Standard Deviation 7.5635 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 4, 72 hours postdose | -4.83 units on a scale | Standard Deviation 6.2 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 3, 48 hours postdose | -2.30 units on a scale | Standard Deviation 9.936 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 4, 72 hours postdose | -2.67 units on a scale | Standard Deviation 8.446 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | -0.63 units on a scale | Standard Deviation 9.033 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -0.171 units on a scale | Standard Deviation 6.8216 |
| Placebo (Part A) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | 0.90 units on a scale | Standard Deviation 6.872 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -3.63 units on a scale | Standard Deviation 5.126 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 8, 24 hours postdose | -2.87 units on a scale | Standard Deviation 5.731 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 8, 24 hours postdose | -2.282 units on a scale | Standard Deviation 3.6448 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 8, 24 hours postdose | -7.75 units on a scale | Standard Deviation 19.263 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | 7.058 units on a scale | Standard Deviation 12.2168 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | -7.33 units on a scale | Standard Deviation 18.384 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -1.80 units on a scale | Standard Deviation 4.818 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | -10.92 units on a scale | Standard Deviation 18.4 |
| KM-819 30 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | 0.093 units on a scale | Standard Deviation 6.007 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | 3.23 units on a scale | Standard Deviation 5.251 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | 0.25 units on a scale | Standard Deviation 3.504 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 8, 24 hours postdose | -3.27 units on a scale | Standard Deviation 2.738 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -5.687 units on a scale | Standard Deviation 9.4737 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -2.23 units on a scale | Standard Deviation 5.076 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | 3.445 units on a scale | Standard Deviation 11.199 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | 1.33 units on a scale | Standard Deviation 5.654 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 8, 24 hours postdose | -8.835 units on a scale | Standard Deviation 8.3161 |
| KM-819 100 mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 8, 24 hours postdose | 6.75 units on a scale | Standard Deviation 14.754 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | 2.52 units on a scale | Standard Deviation 18.349 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -5.12 units on a scale | Standard Deviation 2.674 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 8, 24 hours postdose | -0.40 units on a scale | Standard Deviation 2.429 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -0.222 units on a scale | Standard Deviation 10.7325 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 8, 24 hours postdose | 1.90 units on a scale | Standard Deviation 7.171 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | 9.264 units on a scale | Standard Deviation 21.435 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | -1.00 units on a scale | Standard Deviation 36.447 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | -8.40 units on a scale | Standard Deviation 13.093 |
| KM-819 200mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 8, 24 hours postdose | 3.842 units on a scale | Standard Deviation 9.4304 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -0.976 units on a scale | Standard Deviation 6.2563 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | -4.668 units on a scale | Standard Deviation 4.6964 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 8, 24 hours postdose | -1.44 units on a scale | Standard Deviation 7.249 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | 0.96 units on a scale | Standard Deviation 3.542 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 8, 24 hours postdose | -6.10 units on a scale | Standard Deviation 18.301 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | -7.70 units on a scale | Standard Deviation 20.092 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | 2.16 units on a scale | Standard Deviation 9.459 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 8, 24 hours postdose | -7.358 units on a scale | Standard Deviation 4.742 |
| KM-819 400mg (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | -12.30 units on a scale | Standard Deviation 16.01 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -4.43 units on a scale | Standard Deviation 5.321 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | -0.128 units on a scale | Standard Deviation 8.7694 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -7.13 units on a scale | Standard Deviation 6.565 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | 4.00 units on a scale | Standard Deviation 17.593 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 8, 24 hours postdose | -6.683 units on a scale | Standard Deviation 15.6554 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 8, 24 hours postdose | 10.25 units on a scale | Standard Deviation 16.825 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | -3.760 units on a scale | Standard Deviation 6.2182 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 8, 24 hours postdose | -8.27 units on a scale | Standard Deviation 8.068 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | 8.25 units on a scale | Standard Deviation 16.121 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness- Day 1, 3 hours postdose | 2.088 units on a scale | Standard Deviation 8.4283 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 2, 24 hours postdose | -1.58 units on a scale | Standard Deviation 2.978 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 8, 24 hours postdose | -1.76 units on a scale | Standard Deviation 6.983 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 2, 24 hours postdose | 0.566 units on a scale | Standard Deviation 8.2926 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 2, 24 hours postdose | 1.25 units on a scale | Standard Deviation 6.233 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Alertness-Day 8, 24 hours postdose | -2.834 units on a scale | Standard Deviation 6.5374 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 8, 24 hours postdose | 1.40 units on a scale | Standard Deviation 10.538 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Calmness-Day 1, 3 hours postdose | 1.40 units on a scale | Standard Deviation 6.728 |
| Placebo (Part B) | Change From Baseline for Bond and Lader Visual Analogue Scale (VAS) | Contentedness-Day 1, 3 hours postdose | -0.42 units on a scale | Standard Deviation 3.294 |
Secondary
Change From Baseline Phospho-Tau in CSF (Part B)
To evaluate Phospho-Tau of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing)
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Value (MEAN) |
|---|---|---|
| KM-819 - 10 mg (Part A) | Change From Baseline Phospho-Tau in CSF (Part B) | 6.4132 pg/mL |
| KM-819 - 30 mg (Part A) | Change From Baseline Phospho-Tau in CSF (Part B) | 0.2072 pg/mL |
| KM-819 - 100mg (Part A) | Change From Baseline Phospho-Tau in CSF (Part B) | 4.4672 pg/mL |
| KM-819 200mg (Part A) | Change From Baseline Phospho-Tau in CSF (Part B) | 6.7032 pg/mL |
| KM-819 - 400mg (Part A) | Change From Baseline Phospho-Tau in CSF (Part B) | 5.1606 pg/mL |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline Phospho-Tau in CSF (Part B) | 5.3123 pg/mL |
Secondary
Change From Baseline Total Tau in CSF (Part B)
To evaluate Total Tau in CSF of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: CSF - Part B: Day 1 (at -120 minutes to 0 minute prior to the first dosing) and on Day 7 (at 1 hour after last dosing)
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Value (MEAN) |
|---|---|---|
| KM-819 - 10 mg (Part A) | Change From Baseline Total Tau in CSF (Part B) | 60.3043 pg/mL |
| KM-819 - 30 mg (Part A) | Change From Baseline Total Tau in CSF (Part B) | 9.2313 pg/mL |
| KM-819 - 100mg (Part A) | Change From Baseline Total Tau in CSF (Part B) | -3.1593 pg/mL |
| KM-819 200mg (Part A) | Change From Baseline Total Tau in CSF (Part B) | 27.8648 pg/mL |
| KM-819 - 400mg (Part A) | Change From Baseline Total Tau in CSF (Part B) | 29.2961 pg/mL |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Change From Baseline Total Tau in CSF (Part B) | 20.8198 pg/mL |
Secondary
CL/F (Apparent Oral Clearance)
To evaluate the CL/F of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | CL/F (Apparent Oral Clearance) | Part A | 16830 mL/h | Geometric Coefficient of Variation 24.4 |
| KM-819 - 30 mg (Part A) | CL/F (Apparent Oral Clearance) | Part A | 17340 mL/h | Geometric Coefficient of Variation 17.3 |
| KM-819 - 100mg (Part A) | CL/F (Apparent Oral Clearance) | Part A | 20530 mL/h | Geometric Coefficient of Variation 30.8 |
| KM-819 200mg (Part A) | CL/F (Apparent Oral Clearance) | Part A | 27260 mL/h | Geometric Coefficient of Variation 51.9 |
| KM-819 - 400mg (Part A) | CL/F (Apparent Oral Clearance) | Part A | 31650 mL/h | Geometric Coefficient of Variation 36.1 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | CL/F (Apparent Oral Clearance) | Part A | 18230 mL/h | Geometric Coefficient of Variation 9.8 |
| Placebo (Part A) | CL/F (Apparent Oral Clearance) | Part B-Day 7 | 19090 mL/h | Geometric Coefficient of Variation 24.8 |
| Placebo (Part A) | CL/F (Apparent Oral Clearance) | Part B-Day 1 | 17520 mL/h | Geometric Coefficient of Variation 22.4 |
| KM-819 30 mg (Part B) | CL/F (Apparent Oral Clearance) | Part B-Day 1 | 25740 mL/h | Geometric Coefficient of Variation 41.5 |
| KM-819 30 mg (Part B) | CL/F (Apparent Oral Clearance) | Part B-Day 7 | 28760 mL/h | Geometric Coefficient of Variation 17.9 |
| KM-819 100 mg (Part B) | CL/F (Apparent Oral Clearance) | Part B-Day 1 | 19860 mL/h | Geometric Coefficient of Variation 30.8 |
| KM-819 100 mg (Part B) | CL/F (Apparent Oral Clearance) | Part B-Day 7 | 24930 mL/h | Geometric Coefficient of Variation 7.7 |
| KM-819 200mg (Part B) | CL/F (Apparent Oral Clearance) | Part B-Day 7 | 20480 mL/h | Geometric Coefficient of Variation 96.4 |
| KM-819 400mg (Part B) | CL/F (Apparent Oral Clearance) | Part B-Day 7 | 12300 mL/h | Geometric Coefficient of Variation 34.1 |
| KM-819 400mg (Part B) | CL/F (Apparent Oral Clearance) | Part B-Day 1 | 10780 mL/h | Geometric Coefficient of Variation 57.8 |
Secondary
Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile)
To evaluate Cmax of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A: Day1 to Day 4. Part B: Day-1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| KM-819 - 10 mg (Part A) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 244.1 ng/mL | Geometric Coefficient of Variation 31.4 |
| KM-819 - 30 mg (Part A) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 503.6 ng/mL | Geometric Coefficient of Variation 28 |
| KM-819 - 100mg (Part A) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 1152 ng/mL | Geometric Coefficient of Variation 36.7 |
| KM-819 200mg (Part A) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 1879 ng/mL | Geometric Coefficient of Variation 55.3 |
| KM-819 - 400mg (Part A) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 2767 ng/mL | Geometric Coefficient of Variation 43.4 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 1766 ng/mL | Geometric Coefficient of Variation 26 |
| Placebo (Part A) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 512.0 ng/mL | Geometric Coefficient of Variation 30.9 |
| KM-819 30 mg (Part B) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 1009 ng/mL | Geometric Coefficient of Variation 33 |
| KM-819 100 mg (Part B) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 1465 ng/mL | Geometric Coefficient of Variation 77.2 |
| KM-819 200mg (Part B) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 3163 ng/mL | Geometric Coefficient of Variation 50.7 |
| KM-819 400mg (Part B) | Cmax (Maximum Plasma Concentration Determined Directly From the Concentration-time Profile) | 3542 ng/mL | Geometric Coefficient of Variation 76.4 |
Secondary
Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV)
The K-WAIS-IV consists of an assessment of the cognitive ability using a core battery of 10 unique subtests (Block Design, Similarities, Digit Span, Matrix Reasoning, Vocabulary, Arithmetic, Symbol Search, Visual Puzzles, Information, and Coding) that focus on four specific domains of intelligence: verbal comprehension, perceptual reasoning, working memory, and processing speed. The Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index (standard scores: mean=100, standard deviation=15) that are all based on a number of core and supplemental subtests (scaled scores: mean=15, standard deviation=3) that provide pertinent clinical information and flexibility in implementation. The higher values represent a better outcome.
Time frame: Part A: Day 1; Part B: Day 7
Population: All subjects who received at least one dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 12.8 Intelligence quotient (IQ) | Standard Deviation 14.95 |
| KM-819 - 10 mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 6.2 Intelligence quotient (IQ) | Standard Deviation 10.05 |
| KM-819 - 10 mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 6.5 Intelligence quotient (IQ) | Standard Deviation 14.53 |
| KM-819 - 30 mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 4.5 Intelligence quotient (IQ) | Standard Deviation 7.82 |
| KM-819 - 30 mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | -0.3 Intelligence quotient (IQ) | Standard Deviation 8.73 |
| KM-819 - 30 mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | -1.7 Intelligence quotient (IQ) | Standard Deviation 8.07 |
| KM-819 - 100mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 2.7 Intelligence quotient (IQ) | Standard Deviation 8.43 |
| KM-819 - 100mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | -3.8 Intelligence quotient (IQ) | Standard Deviation 16.18 |
| KM-819 - 100mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 3.0 Intelligence quotient (IQ) | Standard Deviation 14.99 |
| KM-819 200mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 10.2 Intelligence quotient (IQ) | Standard Deviation 10.34 |
| KM-819 200mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 2.2 Intelligence quotient (IQ) | Standard Deviation 8.04 |
| KM-819 200mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 8.7 Intelligence quotient (IQ) | Standard Deviation 9.79 |
| KM-819 - 400mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 4.8 Intelligence quotient (IQ) | Standard Deviation 6.94 |
| KM-819 - 400mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 6.0 Intelligence quotient (IQ) | Standard Deviation 8.88 |
| KM-819 - 400mg (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 9.5 Intelligence quotient (IQ) | Standard Deviation 7.66 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 7.3 Intelligence quotient (IQ) | Standard Deviation 5.82 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 3.3 Intelligence quotient (IQ) | Standard Deviation 5.24 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 3.3 Intelligence quotient (IQ) | Standard Deviation 7.5 |
| Placebo (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 3.3 Intelligence quotient (IQ) | Standard Deviation 7.97 |
| Placebo (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 2.5 Intelligence quotient (IQ) | Standard Deviation 8.87 |
| Placebo (Part A) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 4.4 Intelligence quotient (IQ) | Standard Deviation 12.62 |
| KM-819 30 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 3.7 Intelligence quotient (IQ) | Standard Deviation 6.5 |
| KM-819 30 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, pre-dose | 10.5 Intelligence quotient (IQ) | Standard Deviation 10.33 |
| KM-819 30 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 6 hours postdose | 13.7 Intelligence quotient (IQ) | Standard Deviation 21.16 |
| KM-819 30 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 12.7 Intelligence quotient (IQ) | Standard Deviation 10.39 |
| KM-819 30 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 12 hours postdose | 17.8 Intelligence quotient (IQ) | Standard Deviation 20.94 |
| KM-819 30 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 1.7 Intelligence quotient (IQ) | Standard Deviation 5.5 |
| KM-819 30 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 3 hours postdose | 15.8 Intelligence quotient (IQ) | Standard Deviation 13.88 |
| KM-819 100 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 12 hours postdose | 30.3 Intelligence quotient (IQ) | Standard Deviation 12.48 |
| KM-819 100 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 4.7 Intelligence quotient (IQ) | Standard Deviation 3.72 |
| KM-819 100 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 4.3 Intelligence quotient (IQ) | Standard Deviation 6.41 |
| KM-819 100 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 3 hours postdose | 19.7 Intelligence quotient (IQ) | Standard Deviation 6.74 |
| KM-819 100 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 13.2 Intelligence quotient (IQ) | Standard Deviation 4.26 |
| KM-819 100 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 6 hours postdose | 27.2 Intelligence quotient (IQ) | Standard Deviation 6.21 |
| KM-819 100 mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, pre-dose | 22.2 Intelligence quotient (IQ) | Standard Deviation 13.29 |
| KM-819 200mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 11.2 Intelligence quotient (IQ) | Standard Deviation 7.66 |
| KM-819 200mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 3 hours postdose | 24.6 Intelligence quotient (IQ) | Standard Deviation 10.41 |
| KM-819 200mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 12 hours postdose | 24.4 Intelligence quotient (IQ) | Standard Deviation 9.29 |
| KM-819 200mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 2.2 Intelligence quotient (IQ) | Standard Deviation 7.22 |
| KM-819 200mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 2.0 Intelligence quotient (IQ) | Standard Deviation 15.12 |
| KM-819 200mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 6 hours postdose | 22.0 Intelligence quotient (IQ) | Standard Deviation 16.32 |
| KM-819 200mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, pre-dose | 17.6 Intelligence quotient (IQ) | Standard Deviation 6.77 |
| KM-819 400mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 0.0 Intelligence quotient (IQ) | Standard Deviation 16.69 |
| KM-819 400mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 1.2 Intelligence quotient (IQ) | Standard Deviation 4.09 |
| KM-819 400mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | -1.4 Intelligence quotient (IQ) | Standard Deviation 10.21 |
| KM-819 400mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, pre-dose | 11.0 Intelligence quotient (IQ) | Standard Deviation 8.72 |
| KM-819 400mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 3 hours postdose | 12.2 Intelligence quotient (IQ) | Standard Deviation 9.76 |
| KM-819 400mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 6 hours postdose | 14.8 Intelligence quotient (IQ) | Standard Deviation 12.03 |
| KM-819 400mg (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 12 hours postdose | 18.8 Intelligence quotient (IQ) | Standard Deviation 8.26 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 7.0 Intelligence quotient (IQ) | Standard Deviation 5.33 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 5.5 Intelligence quotient (IQ) | Standard Deviation 4.97 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 12 hours postdose | 11.7 Intelligence quotient (IQ) | Standard Deviation 3.78 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | 1.2 Intelligence quotient (IQ) | Standard Deviation 4.45 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 6 hours postdose | 12.3 Intelligence quotient (IQ) | Standard Deviation 5.39 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, pre-dose | 10.3 Intelligence quotient (IQ) | Standard Deviation 5.57 |
| KM-819 200mg (Elderly Male Subjects) (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 3 hours postdose | 10.2 Intelligence quotient (IQ) | Standard Deviation 5.12 |
| Placebo (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 12 hours postdose | 12.8 Intelligence quotient (IQ) | Standard Deviation 20.87 |
| Placebo (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 3 hours postdose | 6.6 Intelligence quotient (IQ) | Standard Deviation 21.76 |
| Placebo (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 12 hours postdose | 6.2 Intelligence quotient (IQ) | Standard Deviation 19.52 |
| Placebo (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 6 hours postdose | 2.9 Intelligence quotient (IQ) | Standard Deviation 13.62 |
| Placebo (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, 6 hours postdose | 13.6 Intelligence quotient (IQ) | Standard Deviation 22.47 |
| Placebo (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 1, 3 hours postdose | -1.6 Intelligence quotient (IQ) | Standard Deviation 16.19 |
| Placebo (Part B) | Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) | Day 7, pre-dose | 7.3 Intelligence quotient (IQ) | Standard Deviation 19.8 |
Secondary
Rac(AUC) (Observed Accumulation by AUC) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| KM-819 - 10 mg (Part A) | Rac(AUC) (Observed Accumulation by AUC) (Part B) | 0.8926 ratio |
| KM-819 - 30 mg (Part A) | Rac(AUC) (Observed Accumulation by AUC) (Part B) | 0.9727 ratio |
| KM-819 - 100mg (Part A) | Rac(AUC) (Observed Accumulation by AUC) (Part B) | 0.7568 ratio |
| KM-819 200mg (Part A) | Rac(AUC) (Observed Accumulation by AUC) (Part B) | 1.485 ratio |
| KM-819 - 400mg (Part A) | Rac(AUC) (Observed Accumulation by AUC) (Part B) | 0.9241 ratio |
Secondary
Rac (Cmax) (Observed Accumulation by Cmax) (Part B)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part B: Day 1 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1, 2, 4, 6, 8, and 12 hours postdose, predose on Days 2, 3, 4, 5, 6, and on Day 7 predose (within 30 minutes prior to study drug administration) and 0.25, 0.5, 1,
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| KM-819 - 10 mg (Part A) | Rac (Cmax) (Observed Accumulation by Cmax) (Part B) | 0.8173 ratio |
| KM-819 - 30 mg (Part A) | Rac (Cmax) (Observed Accumulation by Cmax) (Part B) | 1.003 ratio |
| KM-819 - 100mg (Part A) | Rac (Cmax) (Observed Accumulation by Cmax) (Part B) | 0.6227 ratio |
| KM-819 200mg (Part A) | Rac (Cmax) (Observed Accumulation by Cmax) (Part B) | 1.117 ratio |
| KM-819 - 400mg (Part A) | Rac (Cmax) (Observed Accumulation by Cmax) (Part B) | 0.9122 ratio |
Secondary
Ratio of CSF Concentration/Plasma Cmax (Part B)
Ratio of CSF concentration/Plasma Cmax
Time frame: Plasma - Part B: Day 7 (at 1 hour after last dosing) / CSF - Part B: on Day 7 (at 1 hour after last dosing)
Population: All subjects who received at least one dose in Part B
| Arm | Measure | Value (MEAN) |
|---|---|---|
| KM-819 - 10 mg (Part A) | Ratio of CSF Concentration/Plasma Cmax (Part B) | 0.00067004 Ratio |
| KM-819 - 30 mg (Part A) | Ratio of CSF Concentration/Plasma Cmax (Part B) | 0.00074179 Ratio |
| KM-819 - 100mg (Part A) | Ratio of CSF Concentration/Plasma Cmax (Part B) | 0.00048832 Ratio |
| KM-819 200mg (Part A) | Ratio of CSF Concentration/Plasma Cmax (Part B) | 0.00031749 Ratio |
Secondary
t½ (Apparent Terminal Elimination Half Life)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects. To evaluate the PK and PD of single and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A: Day 1 to Day 4. Part B: Day1 to Day 8
Population: All subjects who received at least one dose
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | t½ (Apparent Terminal Elimination Half Life) | Part A | 1.786 Hours | Geometric Coefficient of Variation 28.3 |
| KM-819 - 30 mg (Part A) | t½ (Apparent Terminal Elimination Half Life) | Part A | 4.791 Hours | Geometric Coefficient of Variation 25 |
| KM-819 - 100mg (Part A) | t½ (Apparent Terminal Elimination Half Life) | Part A | 9.159 Hours | Geometric Coefficient of Variation 41.2 |
| KM-819 200mg (Part A) | t½ (Apparent Terminal Elimination Half Life) | Part A | 9.010 Hours | Geometric Coefficient of Variation 71.6 |
| KM-819 - 400mg (Part A) | t½ (Apparent Terminal Elimination Half Life) | Part A | 8.527 Hours | Geometric Coefficient of Variation 63.2 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | t½ (Apparent Terminal Elimination Half Life) | Part A | 10.55 Hours | Geometric Coefficient of Variation 28.5 |
| Placebo (Part A) | t½ (Apparent Terminal Elimination Half Life) | Part B | 3.075 Hours | Geometric Coefficient of Variation 46.9 |
| KM-819 30 mg (Part B) | t½ (Apparent Terminal Elimination Half Life) | Part B | 5.417 Hours | Geometric Coefficient of Variation 15.1 |
| KM-819 100 mg (Part B) | t½ (Apparent Terminal Elimination Half Life) | Part B | 5.785 Hours | Geometric Coefficient of Variation 24.1 |
| KM-819 400mg (Part B) | t½ (Apparent Terminal Elimination Half Life) | Part B | 4.389 Hours | Geometric Coefficient of Variation 13.4 |
Secondary
Tlag (Lag Time)
To evaluate the T lag of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A: Day1 to Day 4. Part B: Day 1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | Tlag (Lag Time) | Part A | 0.08333 Hours | Standard Deviation 0.1291 |
| KM-819 - 30 mg (Part A) | Tlag (Lag Time) | Part A | 0 Hours | Standard Deviation 0 |
| KM-819 - 100mg (Part A) | Tlag (Lag Time) | Part A | 0 Hours | Standard Deviation 0 |
| KM-819 200mg (Part A) | Tlag (Lag Time) | Part A | 0.04167 Hours | Standard Deviation 0.1021 |
| KM-819 - 400mg (Part A) | Tlag (Lag Time) | Part A | 0 Hours | Standard Deviation 0 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Tlag (Lag Time) | Part A | 0 Hours | Standard Deviation 0 |
| Placebo (Part A) | Tlag (Lag Time) | Part B-Day 7 | 0 Hours | Standard Deviation 0 |
| Placebo (Part A) | Tlag (Lag Time) | Part B-Day 1 | 0.04167 Hours | Standard Deviation 0.1021 |
| KM-819 30 mg (Part B) | Tlag (Lag Time) | Part B-Day 1 | 0.08333 Hours | Standard Deviation 0.1291 |
| KM-819 30 mg (Part B) | Tlag (Lag Time) | Part B-Day 7 | 0 Hours | Standard Deviation 0 |
| KM-819 100 mg (Part B) | Tlag (Lag Time) | Part B-Day 1 | 0 Hours | Standard Deviation 0 |
| KM-819 100 mg (Part B) | Tlag (Lag Time) | Part B-Day 7 | 0 Hours | Standard Deviation 0 |
| KM-819 200mg (Part B) | Tlag (Lag Time) | Part B-Day 1 | 0 Hours | Standard Deviation 0 |
| KM-819 200mg (Part B) | Tlag (Lag Time) | Part B-Day 7 | 0 Hours | Standard Deviation 0 |
| KM-819 400mg (Part B) | Tlag (Lag Time) | Part B-Day 7 | 0 Hours | Standard Deviation 0 |
| KM-819 400mg (Part B) | Tlag (Lag Time) | Part B-Day 1 | 0 Hours | Standard Deviation 0 |
Secondary
Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile)
To evaluate the pharmacokinetics and pharmacodynamics of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects and multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A:Day 1 to 4; Part B: Day 1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| KM-819 - 10 mg (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A | 1.500 hours |
| KM-819 - 30 mg (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A | 1.000 hours |
| KM-819 - 100mg (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A | 2.000 hours |
| KM-819 200mg (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A | 2.008 hours |
| KM-819 - 400mg (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A | 4.000 hours |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part A | 2.000 hours |
| Placebo (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 7 | 2.000 hours |
| Placebo (Part A) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 1 | 2.000 hours |
| KM-819 30 mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 1 | 2.000 hours |
| KM-819 30 mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 7 | 3.000 hours |
| KM-819 100 mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 1 | 3.000 hours |
| KM-819 100 mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 7 | 4.000 hours |
| KM-819 200mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 1 | 2.008 hours |
| KM-819 200mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 7 | 2.000 hours |
| KM-819 400mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 7 | 2.017 hours |
| KM-819 400mg (Part B) | Tmax (Time to Achieve Maximum Observed Plasma Concentration Determined Directly From the Concentration-time Profile) | Part B-Day 1 | 2.000 hours |
Secondary
Vz/F (Apparent Volume of Distribution)
To evaluate Vz/F of single and multiple ascending oral doses of KM-819 in healthy young adult male subjects multiple oral doses of KM-819 in elderly male subjects.
Time frame: Part A: Day 1 to 4; Part B: Day 1 to Day 8
Population: All subjects who received at least one dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| KM-819 - 10 mg (Part A) | Vz/F (Apparent Volume of Distribution) | Part A | 43370 mL | Geometric Coefficient of Variation 18.8 |
| KM-819 - 30 mg (Part A) | Vz/F (Apparent Volume of Distribution) | Part A | 119800 mL | Geometric Coefficient of Variation 23.5 |
| KM-819 - 100mg (Part A) | Vz/F (Apparent Volume of Distribution) | Part A | 271200 mL | Geometric Coefficient of Variation 56.6 |
| KM-819 200mg (Part A) | Vz/F (Apparent Volume of Distribution) | Part A | 354300 mL | Geometric Coefficient of Variation 114 |
| KM-819 - 400mg (Part A) | Vz/F (Apparent Volume of Distribution) | Part A | 389300 mL | Geometric Coefficient of Variation 49.5 |
| KM-819 200mg (Elderly Male Subjects) (Part A) | Vz/F (Apparent Volume of Distribution) | Part A | 277500 mL | Geometric Coefficient of Variation 27.3 |
| Placebo (Part A) | Vz/F (Apparent Volume of Distribution) | Part B-Day1 | 77710 mL | Geometric Coefficient of Variation 32.9 |
| Placebo (Part A) | Vz/F (Apparent Volume of Distribution) | Part B-Day7 | 143400 mL | Geometric Coefficient of Variation 33.5 |
| KM-819 30 mg (Part B) | Vz/F (Apparent Volume of Distribution) | Part B-Day1 | 201200 mL | Geometric Coefficient of Variation 57.6 |
| KM-819 30 mg (Part B) | Vz/F (Apparent Volume of Distribution) | Part B-Day7 | 241300 mL | Geometric Coefficient of Variation 23.6 |
| KM-819 100 mg (Part B) | Vz/F (Apparent Volume of Distribution) | Part B-Day1 | 165700 mL | Geometric Coefficient of Variation 58.1 |
| KM-819 100 mg (Part B) | Vz/F (Apparent Volume of Distribution) | Part B-Day7 | 171400 mL | Geometric Coefficient of Variation 7.4 |
| KM-819 200mg (Part B) | Vz/F (Apparent Volume of Distribution) | Part B-Day7 | 187100 mL | Geometric Coefficient of Variation 151.8 |
| KM-819 400mg (Part B) | Vz/F (Apparent Volume of Distribution) | Part B-Day7 | 88200 mL | Geometric Coefficient of Variation 64.9 |
| KM-819 400mg (Part B) | Vz/F (Apparent Volume of Distribution) | Part B-Day1 | 68250 mL | Geometric Coefficient of Variation 72.8 |