Study to Evaluate the PK, Relative Bioavailability and Safety of TG-2349 With Single Oral Dose Under Fed Condition in Healthy Volunteers

TG-2349 oral solution has been investigated in a phase I/IIa study (study number: TG-2349-01) in healthy volunteers and patients with chronic hepatitis C (CHC) infection. The study demonstrated that TG-2349 was safe and well-tolerated when given to healthy volunteers at single oral doses up to 800 mg, and at five-consecutive daily oral doses up to 600 mg. Co-administration of TG-2349 with food resulted in a significant increase in bioavailability, and therefore concomitant food intake with dosing is recommended.

To further advance the clinical development of TG-2349, a new capsule formulation was developed to replace the current TG-2349 oral solution. The objectives of this study (study number: TG-2349-02) are to evaluate the PK and relative bioavailability of TG-2349, given as a new capsule formulation and as the original formulation of oral solution, after a single oral dose of 400 mg under fed condition in healthy volunteers, and to evaluate the safety, tolerability, and ethnic differences of the TG-2349 capsule formulation.

Inclusion criteria

at Screening

• East Asian or Caucasian subjects, male or female, and 18 to 40 years of age inclusive
• Body mass index (BMI) in the range of 19.0 to 30.0 kg/m2 and body weight ≥ 50 kg inclusive
• In general good physical and mental health status on the basis of a medical history review, medical evaluation including vital signs and physical examination, 12-lead ECG, and laboratory results at screening
• For females, one of the following criteria must be fulfilled:

(1)At least 1 year post menopausal, or (2)Surgically sterile, or (3)Willing to use a double-barrier method (intrauterine device [IUD] plus condom, spermicidal gel plus condom) of contraception from screening until 30 days after the last dose of study drug; 5.Males must be willing to use a reliable form of contraception (use of a condom or a partner fulfilling the above criteria) from screening until 30 days after the last dose of study drug 6.Willing to abstain from caffeine- or xanthine-containing beverages (including coffee and tea), alcohol, grapefruit juice, and Seville oranges during the stay-on-site period 7.Willing and able to provide written informed consent

Exclusion criteria

at Screening

• Positive serological test for IgM anti-HAV antibody, HbsAg, or anti-HCV antibody at screening
• Positive ELISA test for HIV-1 or HIV-2 at screening
• Any of the following abnormal laboratory values at screening: Hemoglobin (Hb) <12.0g/dL for women and <13.0g/dL for men, white blood cell count (WBC) <3,000 cells/mm3, absolute neutrophil count <1,500 cells/mm3, platelet count <100,000 cells/mm3, serum creatinine ≥ 2 mg/dL, ALT or AST levels ≥ 2 xULN, total bilirubin ≥ 1.5 xULN, INR (International Normalized Ratios for prothrombin time) ≥1.5 xULN
• Any abnormal laboratory values that are considered clinically significant by the Investigator at screening
• QTcF greater than 450 msec for females and 430 msec for males at screening
• History of renal, hepatic impairment, stomach or intestinal surgery or resection, malabsorption syndrome
• History of seizures, epilepsy, cardiovascular, diabetes, or cancer (except basal cell carcinoma)
• History or family history of prolonged QT interval or family history of sudden cardiac death at a young age (< 30 years )
• History of drug allergy or hypersensitivity, especially to sulfa drugs
• History or evidence of abuse of alcohol, barbiturate, amphetamine, recreational, or narcotic drug use within 6 months prior to first dose of study drug administration
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of a psychiatric illness, or who have any history of suicide attempt or depression
• Anemia or blood/plasma donation within 30 days prior to first dose of study drug administration
• Pregnant or breast-feeding
• Use of tobacco or nicotine-containing products within 30 days prior to first dose of study drug administration
• Use of concomitant medication, including herbal remedies and dietary supplements (except for paracetamol/acetaminophen, ibuprofen, and hormonal contraceptives) within 14 days prior to first dose of study drug administration
• Received any other investigational drug within 30 days prior to first dose of study drug administration

Exclusion criteria

at the First Admission

• Any of the following abnormal laboratory values at admission: Hb <12.0g/dL for women and <13.0g/dL for men, WBC <3,000 cells/mm3, absolute neutrophil count <1,500 cells/mm3, platelet count <100,000 cells/mm3, serum creatinine ≥ 2 mg/dL, ALT or AST levels ≥ 2 xULN, total bilirubin ≥ 1.5 xULN, INR ≥ 1.5 xULN
• Any abnormal laboratory values that are considered clinically significant by the Investigator at admission
• Any clinically significant abnormality on 12-lead ECG or a QTcF greater than 450 msec for females and 430 msec for males at admission
• Positive urine drug screen or breath alcohol test at admission
• If female, positive serum pregnancy test at admission
• Acute illness within 2 weeks prior to dosing, unless approved by the Sponsor's Medical Monitor