Kainos Medicine Inc.
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, Pharmacokinetics (PK), and Pharmacodynamics (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. The food effect will be investigated in one of the single dose cohorts of young adult male subjects, who will be crossed-over to the fed condition. Once the dose level is selected for the crossed-over to the fed condition and elderly subjects, the protocol will be amended to specify the dose level. 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. One of the cohorts will be crossed-over to the fed condition to assess the effect of food as decided by Investigator and Sponsor during the study after completion of the 2nd dose cohort (30 mg). Eight elderly male or post-menopausal female subjects will be enrolled into an additional cohort; 6 subjects will receive KM-819 at a dose level not exceeding the highest dose tested in the young adult male cohorts 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. The cohort that crossed-over to the fed condition will undergo the same procedure up to the Outpatient Visit on Day 4. Subjects will be confined for 3 days for the second time, and are required to return for outpatient Visit 5 (Day 4), Visit 6 (Day 7), and for a Follow up Visit 7 (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 KM-819 at a dose level not exceeding the highest dose tested in the young adult male cohorts and 2 subjects will receive placebo.
- Drug: KM-819
- Drug: Placebo
|Ages eligible for Study||19 Years and older|
|Genders eligible for Study||All|
|Accepts Healthy Volunteers||Accepts Healthy Volunteers|
- 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.
- 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 upper limit of normal (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.
- 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 < 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.
- Subject has a mean QT interval corrected for heart rate according to Fridericia (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.
- 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.
- Subject has had any use of tobacco- or nicotine-containing products within 6 months prior to Screening.
- 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.
- Subject has used any drugs-of-abuse within 3 months before check in.
- Subject has used any inducers of metabolism (e.g., barbiturates, rifampin) in the 3 months prior to check-in.
- 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.
- 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).
- 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.
- Subject has (recent history of) any other condition which, in the opinion of the Investigator, precludes the subject's participation in the trial.
- Subject is an employee of the Kainos Medicine, Inc. or vendors involved in the study. Additional Exclusion Criteria for Young Adult Subjects
- For young adult cohorts, subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, as judged by the Investigator or designee. Exclusion Criteria for Elderly Subjects Replacement for Exclusion No. 8 above 8. Subject has a mean pulse < 50 or > 90 bpm; mean SBP > 160 mmHg; mean DBP > 100 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically). Replacement for Exclusion No. 21 above 21. For elderly cohorts, subject has any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy that is not well managed and stable, as judged by the Investigator or designee. Additional Exclusion Criteria 22. Elderly subject is excluded if the Glomerular Filtration Rate (calculated based on Cockcroft-Gault formula) is < 60 mL/min/1.73 m2.
- Clinically significant abnormal findings in the lumbar X-ray examination (only for elder subjects for MAD study).
Korea, Republic of (1)
- CHA Bundang Medical Center, CHA UniversityrecruitingSeongnam, Gyeonggi-do, Korea, Republic of, 13496
30 September, 2016
11 January, 2017