Clinical trial NCT01523990: A Study to Evaluate the Safety, Tolerability, and PK in Healthy Volunteers and HCV Genotype 1 Infected Patients
Official title: A Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics Profiles of Single and Multiple Ascending Oral Doses of TG-2349, and Followed by a Dose-Ranging Study in Hepatitis C Genotype 1 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Hepatitis C, Chronic
Lead sponsor: TaiGen Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2012-02-01
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Safety Study to Evaluate the Safety, Tolerability, and Pharmacokinetics in HCV Genotype 1 Infected Patients

Detailed description: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study in Healthy East Asian and Caucasian Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics Profiles of Single and Multiple Ascending Oral Doses of TG-2349, and Followed by a Dose-Ranging Study in Hepatitis C Genotype 1 Infected Patients.

Eligibility criteria: Inclusion Criteria:

* East Asian or Caucasian subjects, male or female, and 18 to 65 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 generally 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
* 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
* 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
* Willing and able to provide written informed consent

Exclusion Criteria:

* 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 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 x ULN, 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
* 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 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

Primary outcomes:
measure: Pharmacokinetics (PK) profiles of single and multiple ascending oral doses of TG-2349 in healthy East Asian and Caucasian volunteers.
timeFrame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
measure: Safety and tolerability of single and multiple ascending oral doses of TG-2349 in healthy East Asian and Caucasian volunteers.
timeFrame: predose, and 2,4,6,8,12,24,48,72,96 hours post-dose
measure: Pharmacokinetics (PK) profiles of multiple oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
timeFrame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
measure: Safety and tolerability of multiple ascending oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
timeFrame: predose, and 4,6,12 hours post-dose
measure: Antiviral activity of multiple ascending oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
timeFrame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Secondary outcomes:
measure: The food effect of TG-2349 in healthy volunteers.
timeFrame: 1 week
measure: Appearance of viral variants if any in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
timeFrame: during and after 3 days of TG-2349 dosing, the 4-week and 1 year follow-up periods
measure: Ethnicity differences in safety and tolerability between East Asian and Caucasian volunteers.
timeFrame: predose, and 2,4,6,8,12,24,48,72,96 hours post-dose
measure: Ethnicity differences in Pharmacokinetics (PK) profiles between East Asian and Caucasian volunteers.
timeFrame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Other outcomes:
Locations:
city: Cypress
country: United States
facility: WCCT
state: California
Study officials:
affiliation: WCCT
name: Nicole Sims, DO
role: PRINCIPAL_INVESTIGATOR
References: