Phase I, KM-819 in Healthy Subjects for Parkinson's Disease

Inclusion Criteria

• 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).
• Male subject should be 19 to 45 years old (for young adult cohorts) or over 60 years old (for elderly cohorts).
• Subject has a body mass index (BMI) range of 18.5 to 30 kg/m2 inclusive at Screening.
• 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
• Male subject must not donate sperm starting at Screening, throughout the study period and for at least 90 days after final study drug administration.
• Female subject must be over 60 years old and post-menopausal (defined as at least 1 year without any menses) prior to Screening.
• Subject agrees not to participate in another investigational study while on study treatment.

Exclusion Criteria

• Subject has a known or suspected hypersensitivity to KM-819, or any components of the formulation(s) used.
• Subject has previously participated in a clinical study with KM-819.
• 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, it cannot be repeated and is exclusionary.
• 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).
• 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.
• 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.
• 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.
• Subject has a mean pulse 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.
• 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.
• 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.

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