A Study to Evaluate the Safety, Tolerability, and PK in Healthy Volunteers and HCV Genotype 1 Infected Patients

TaiGen Biotechnology

Status and phase: Completed; Phase 1

Conditions: Healthy; Hepatitis C, Chronic

Treatments: Drug: placebo; Drug: TG-2349

Study type: Interventional

Funder types: Industry

Identifiers

NCT01523990

TG-2349-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 135 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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135 participants in 27 patient groups, including a placebo group

Panel I (TG-2349)

Experimental group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 50 mg (fasted) to 50 mg (fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: TG-2349

Panel I (placebo)

Placebo Comparator group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 50 mg (fasted) to 50 mg (fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: placebo

Panel II (TG-2349)

Experimental group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 100 mg (fasted) to 100 mg (fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: TG-2349

Panel II (placebo)

Placebo Comparator group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 100 mg (fasted) to 100 mg (fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: placebo

Panel III (TG-2349)

Experimental group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 200 mg (fasted or fed) to 400 mg (fasted or fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: TG-2349

Panel III (placebo)

Placebo Comparator group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 200 mg (fasted or fed) to 400 mg (fasted or fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: placebo

Panel IV (TG-2349)

Experimental group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 600 mg (fasted or fed) to 800 mg (fasted or fed) of TG-2349 with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: TG-2349

Panel IV (placebo)

Placebo Comparator group

Description:

Sequential single oral dose taken by healthy East and Caucasian volunteers from 600 mg (fasted or fed) to 800 mg (fasted or fed) of placebo with 1 week follow-up after each dosage. A washout period of at least 10 days between the 1st and the 2nd dose is required.

Treatment:

Drug: placebo

Panel V (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: TG-2349

Panel V (placebo)

Placebo Comparator group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: placebo

Panel VI (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: TG-2349

Panel VI (placebo)

Placebo Comparator group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: placebo

Panel VII (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: TG-2349

Panel VII (placebo)

Placebo Comparator group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: placebo

Panel VIII (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: TG-2349

Panel VIII (placebo)

Placebo Comparator group

Description:

Oral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers .

Treatment:

Drug: placebo

Panel IX (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 200 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Treatment:

Drug: TG-2349

Panel IX (placebo)

Placebo Comparator group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 200 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Treatment:

Drug: placebo

Panel X (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 400 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Treatment:

Drug: TG-2349

Panel X (placebo)

Placebo Comparator group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 400 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Treatment:

Drug: placebo

Panel XI (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Treatment:

Drug: TG-2349

Panel XI (placebo)

Placebo Comparator group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 1 (including subtypes 1a or 1b or mixed 1a/1b) infected patients.

Treatment:

Drug: placebo

Panel XII (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 2 infected, treatment-naive patients.

Treatment:

Drug: TG-2349

Panel XIII (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 3 infected, treatment-naive patients.

Treatment:

Drug: TG-2349

Panel XIV (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 4 infected, treatment-naive patients.

Treatment:

Drug: TG-2349

Panel XV (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 5 infected, treatment-naive patients.

Treatment:

Drug: TG-2349

Panel XVI (TG-2349)

Experimental group

Description:

Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 6 infected, treatment-naive patients.

Treatment:

Drug: TG-2349