To Determine the Maximum Tolerated Dose (MTD) of HK-001 in Healthy Volunteers
To Determine the Maximum Tolerated Dose (MTD) of HK-001 in Healthy Volunteers
Eligible subjects will receive either different dosages of HK-001 or placebo in a 3:1 ratio
 in 1 of the 7 dose cohorts. After single dose administration, followed by an independent Data
 and Safety Monitoring Board (DSMB) meeting for safety assessments (including the available
 plasma pharmacokinetic profile), the subjects will be allowed to receive (Z)-BP or placebo
 twice a day orally at the study site for 14 consecutive days and follow up on the 28th day
 after the last dose administration by a site visit. The study drugs (including placebo) will
 be administered at the study site by following the investigator's instructions to either
 perform blood sampling for pharmacokinetic evaluation or maximize the treatment compliance.

 There will be 7 cohorts and subjects will be randomized into cohorts consisting of 8 subjects
 each (6 active and 2 placebo controls per cohort). Dose cohorts will be escalated
 sequentially from low to high dose (50 mg, BID; 100 mg, BID; 150 mg, BID; 225 mg, BID; 300
 mg, BID; 400 mg, BID; 525 mg, BID) by following a modified Fibonacci sequence, and based on
 the decision of an independent DSMB at a set time point. Following all subjects of a cohort
 complete the safety and PK evaluation after receiving the last dose administration, a cohort
 at the next dose level will be launched if the DSMB does not identify significant safety
 concerns after reviewing safety data and PK profiles.
Inclusion Criteria:

 1. Subject's age is no less than 20 years old.

 2. Subjects whose body mass index (BMI) at screening is within a range of ≥18.5 kg/m2 and
 <25.0 kg/m2.

 BMI = Body Weight (kg) / [Height (m)]2 And body weight is not less than 50 kg and 45
 kg for males and females, respectively.

 3. Subject's medical history shows no contraindication to the test medications
 [hypersensitivity to (Z)-BP or any component of test and reference products].

 4. Subjects who are judged to be in good health by the investigator based upon the
 results of physical examinations (PEs) and chest X-ray (within 60 days prior to the
 first study dose), and all items of routine laboratory tests, including serum
 biochemistry, hematology and urinalysis, are within normal range as judged by the
 site. Assessment items of blood biochemistry include electrolytes (sodium, potassium,
 chloride, calcium, phosphorus), albumin, total cholesterol, total bilirubin, ALP,
 SGOT, SGPT, GGT, BUN, PT, APPT, serum creatinine, triglyceride, glucose, amylase,
 lipase, ACTH, aldosterone, cortisol, T3, free T4, TSH, and uric acid. Assessment items
 of hematology tests include red blood cell (RBC), white blood cell (WBC) and platelet
 count; differential WBC count including neutrophils, lymphocytes, monocytes,
 eosinophils, and basophils; hemoglobin, and hematocrit. Assessment items of urinalysis
 include appearance, gravity, pH, erythrocyte, leukocyte, epithelial cells, glucose,
 protein, ketones, and nitrite

 5. Female subjects show negative pregnancy test results within 30 days prior to the first
 study dose.

 6. Subjects did not take any of the following medications in the specified durations:

 -  Any medication (except contraceptives) within 14 days prior to the first dose of
 the study

 -  Any enzyme inducer or inhibitor within 30 days prior to the first dose of the
 study

 7. Subjects understood and have signed the written informed consent form.

 Exclusion Criteria:

 1. Subjects with any properly diagnosed disease within 30 days prior to the first dose of
 the study

 2. Subjects with a clinically significant hematological, endocrinal, cardiovascular,
 hepatic, renal, gastrointestinal, and/or pulmonary disorders; subjects with any
 predisposing condition that might interfere with the absorption, distribution,
 metabolism and excretion of drugs; subjects who have had any previous gastrointestinal
 surgery, except appendectomy if performed >90 days prior to the first dose of the
 study

 3. Subjects who have received any known hepatic or renal clearance-altering agents (e.g.,
 erythromycin, cimetidine, barbiturates, phenothiazine, clarithromycin,
 trolearndomycin, ketoconazole, miconazolem fluconazole, itraconazole) for a period of
 up to 30 days prior to the first dose of the study

 4. Subjects had participated in investigational drug trials and took any investigational
 drugs within 60 days prior to the first study dose.

 5. Subjects had blood donation for more than 250 mL within 60 days prior to the first
 dose of the study.

 6. Subjects had a history of drug abuse or alcohol abuse according to DSM IV criteria.

 7. Subjects who are smokers or have smoking history

 8. Subjects who cannot stop caffeine-intakes for 48 hours prior to the first study dose
 and during the entire study period.

 9. Subjects who are pregnant or lactating

 10. For enrollment of female subjects with child-bearing potential, the subject must be
 practicing sexual abstinence or be using and willing to continue to use a medically
 acceptable form of birth control for at least 1 month prior to screening (that period
 will extend to 3 months for oral contraceptive use) and for at least 30 days after the
 last dose of study drug. For a subject to be considered not to be of child-bearing
 potential, she must have been amenorrheic for at least 2 years, or must have had a
 hysterectomy, a bilateral tubal ligation, and/or a bilateral oophorectomy (as
 determined by the medical history). The male partner of a female study subject with
 childbearing potential must use a condom and ensure that his partner uses a suitable
 method of contraception as outlined above.

 11. Subjects who are inappropriate to participate in this study, as judged by the clinical
 investigator

 12. Subjects who have been tested positive for the following tests:

 -  Human immunodeficiency virus (HIV)

 -  Hepatitis B virus (HBV)

 -  Hepatitis C virus (HCV)