HealthyPhase 1NCT01523990
A Study to Evaluate the Safety, Tolerability, and PK in Healthy Volunteers and HCV Genotype 1 Infected Patients
A Phase 1 study testing TG-2349 in people with Healthy and Hepatitis C, Chronic, run by TaiGen Biotechnology Co., Ltd. at 1 site in United States.
Trial summary
A Safety Study to Evaluate the Safety, Tolerability, and Pharmacokinetics in HCV Genotype 1 Infected Patients Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Hepatitis C, Chronic
- What is being tested?
- TG-2349
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Jul 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
- At least 1 year post menopausal, or
- Surgically sterile, or
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- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
About this study
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
A Safety Study to Evaluate the Safety, Tolerability, and Pharmacokinetics in HCV Genotype 1 Infected Patients
Read the 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.
- Conditions
- Healthy, Hepatitis C, Chronic
- Being tested
- TG-2349, placebo
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TG-2349Drug
Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth.
placeboDrug
Available in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes.
| Study group | Role | What they receive |
|---|---|---|
| Panel I (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel I (placebo) | Placebo comparator | 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. Receives: Drug: placebo |
| Panel II (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel II (placebo) | Placebo comparator | 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. Receives: Drug: placebo |
| Panel III (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel III (placebo) | Placebo comparator | 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. Receives: Drug: placebo |
| Panel IV (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel IV (placebo) | Placebo comparator | 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. Receives: Drug: placebo |
| Panel V (TG-2349) | Experimental | Oral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers . Receives: Drug: TG-2349 |
| Panel V (placebo) | Placebo comparator | Oral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers . Receives: Drug: placebo |
| Panel VI (TG-2349) | Experimental | Oral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers . Receives: Drug: TG-2349 |
| Panel VI (placebo) | Placebo comparator | Oral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers . Receives: Drug: placebo |
| Panel VII (TG-2349) | Experimental | Oral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers . Receives: Drug: TG-2349 |
| Panel VII (placebo) | Placebo comparator | Oral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers . Receives: Drug: placebo |
| Panel VIII (TG-2349) | Experimental | Oral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers . Receives: Drug: TG-2349 |
| Panel VIII (placebo) | Placebo comparator | Oral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers . Receives: Drug: placebo |
| Panel IX (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel IX (placebo) | Placebo comparator | 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. Receives: Drug: placebo |
| Panel X (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel X (placebo) | Placebo comparator | 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. Receives: Drug: placebo |
| Panel XI (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel XI (placebo) | Placebo comparator | 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. Receives: Drug: placebo |
| Panel XII (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel XIII (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel XIV (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel XV (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
| Panel XVI (TG-2349) | Experimental | 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. Receives: Drug: TG-2349 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics (PK) profiles of single and multiple ascending oral doses of TG-2349 in healthy East Asian and Caucasian volunteers.
Dose proportionality will be assessed by evaluating PK parameters AUC0-t, AUC0-inf, and Cmax. Parameters that are not dose dependent will be assessed by evaluating Tmax, t1/2, and λz. The linear relationship between the log-transformed PK parameter and the natural log of the dose will be tested using a linear lack-of-fit test. The dose-dependent parameters will not be dose normalized. Residual analysis will be used to assess the assumptions of normality and variance homogeneity for the statistical model.
Measured: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Safety and tolerability of single and multiple ascending oral doses of TG-2349 in healthy East Asian and Caucasian volunteers.
Vital signs, physical examinations, 12-lead ECG, safety laboratory parameter abnormalities, and other toxicities graded by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0 will be examined to evaluate safety profiles of the study treatments. Special attention will be paid to Grade III or IV toxicities in all treatment levels.
Measured: predose, and 2,4,6,8,12,24,48,72,96 hours post-dose
Pharmacokinetics (PK) profiles of multiple oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Dose proportionality will be assessed by evaluating PK parameters AUC0-t, AUC0-inf, and Cmax. Parameters that are not dose dependent will be assessed by evaluating Tmax, t1/2, and λz. The linear relationship between the log-transformed PK parameter and the natural log of the dose will be tested using a linear lack-of-fit test. The dose-dependent parameters will not be dose normalized. Residual analysis will be used to assess the assumptions of normality and variance homogeneity for the statistical model.
Measured: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Safety and tolerability of multiple ascending oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Vital signs, physical examinations, 12-lead ECG, safety laboratory parameter abnormalities, and other toxicities graded by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0 will be examined to evaluate safety profiles of the study treatments. Special attention will be paid to Grade III or IV toxicities in all treatment levels.
Measured: predose, and 4,6,12 hours post-dose
Antiviral activity of multiple ascending oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Descriptive statistics and graphs will be presented for the antiviral variables. Change from pre dose will be analyzed descriptively for each time point after study drug administration. Graphic displays of raw data and changes over time will be performed at each dosing level (plots of raw data of TG-2349 at each time point with mean and median).
The breakthrough is defined as a greater than or equal to 1 log10 increase in HCV RNA above nadir, or detectable HCV RNA, while on treatment, after an initial drop to a level of below the detection. The slope of the plasma viral RNA decrease during the first few days of treatment, any subsequent plasma viral RNA increase observed during and/or after dosing, and all breakthrough events should be recorded and summarized.
Measured: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Secondary outcomes (4)
The food effect of TG-2349 in healthy volunteers.
Food effect will be evaluated at two lower doses of 50 mg and 100 mg in panel I and panel II of the study.The primary PK parameters to investigate the food effect are AUC0-inf, AUC0-24, and Cmax. The secondary PK parameters to investigate the food effect are Tmax, t½, CL.
Measured: 1 week
Appearance of viral variants if any in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Appearance of phenotype and genotype variants potentially arising during the 3-day treatment period and during the 4-week and 1 year follow-up periods.
Measured: during and after 3 days of TG-2349 dosing, the 4-week and 1 year follow-up periods
Ethnicity differences in safety and tolerability between East Asian and Caucasian volunteers.
Vital signs, physical examinations, 12-lead ECG, safety laboratory parameter abnormalities, and other toxicities graded by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0 will be examined to evaluate safety profiles of the study treatments. Special attention will be paid to Grade III or IV toxicities in all treatment levels.
Measured: predose, and 2,4,6,8,12,24,48,72,96 hours post-dose
Ethnicity differences in Pharmacokinetics (PK) profiles between East Asian and Caucasian volunteers.
Dose proportionality will be assessed by evaluating PK parameters AUC0-t, AUC0-inf, and Cmax. Parameters that are not dose dependent will be assessed by evaluating Tmax, t1/2, and λz. The linear relationship between the log-transformed PK parameter and the natural log of the dose will be tested using a linear lack-of-fit test. The dose-dependent parameters will not be dose normalized. Residual analysis will be used to assess the assumptions of normality and variance homogeneity for the statistical model.
Measured: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study startOct 2011
- Primary completionApr 2012
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- TaiGen Biotechnology Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nicole Sims, DO, Principal investigator, WCCT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01523990
- Sponsor's protocol ID
- TG-2349-01
- Status last verified
- Dec 2014
- First submitted
- 13 Oct 2011
- Last updated
- 19 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01523990
- Acronym / sponsor ID
- TG-2349-01
- Conditions
- Healthy, Hepatitis C, Chronic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- TaiGen Biotechnology Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 27
| Arm | Type | Receives |
|---|---|---|
| Panel I (TG-2349) | Experimental | Drug: TG-2349Sequential 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. |
| Panel I (placebo) | Placebo comparator | Drug: placeboSequential 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. |
| Panel II (TG-2349) | Experimental | Drug: TG-2349Sequential 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. |
| Panel II (placebo) | Placebo comparator | Drug: placeboSequential 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. |
| Panel III (TG-2349) | Experimental | Drug: TG-2349Sequential 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. |
| Panel III (placebo) | Placebo comparator | Drug: placeboSequential 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. |
| Panel IV (TG-2349) | Experimental | Drug: TG-2349Sequential 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. |
| Panel IV (placebo) | Placebo comparator | Drug: placeboSequential 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. |
| Panel V (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers . |
| Panel V (placebo) | Placebo comparator | Drug: placeboOral dose taken once daily for 5 consecutive days at dose level of 100 mg taken by healthy East and Caucasian volunteers . |
| Panel VI (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers . |
| Panel VI (placebo) | Placebo comparator | Drug: placeboOral dose taken once daily for 5 consecutive days at dose level of 200 mg taken by healthy East and Caucasian volunteers . |
| Panel VII (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers . |
| Panel VII (placebo) | Placebo comparator | Drug: placeboOral dose taken once daily for 5 consecutive days at dose level of 400 mg taken by healthy East and Caucasian volunteers . |
| Panel VIII (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers . |
| Panel VIII (placebo) | Placebo comparator | Drug: placeboOral dose taken once daily for 5 consecutive days at dose level of 600 mg taken by healthy East and Caucasian volunteers . |
| Panel IX (TG-2349) | Experimental | Drug: TG-2349Oral 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. |
| Panel IX (placebo) | Placebo comparator | Drug: placeboOral 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. |
| Panel X (TG-2349) | Experimental | Drug: TG-2349Oral 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. |
| Panel X (placebo) | Placebo comparator | Drug: placeboOral 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. |
| Panel XI (TG-2349) | Experimental | Drug: TG-2349Oral 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. |
| Panel XI (placebo) | Placebo comparator | Drug: placeboOral 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. |
| Panel XII (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 2 infected, treatment-naive patients. |
| Panel XIII (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 3 infected, treatment-naive patients. |
| Panel XIV (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 4 infected, treatment-naive patients. |
| Panel XV (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 5 infected, treatment-naive patients. |
| Panel XVI (TG-2349) | Experimental | Drug: TG-2349Oral dose taken once daily for 3 consecutive days at dose level of 600 mg (fed) taken by HCV genotype 6 infected, treatment-naive patients. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TG-2349Supplied as oral liquid formulation in pre-filled glass syringe. Two dose strengths, 25 mg TG-2349 (25 mg/mL in PEG 400, 1.1 mL fill) and 200 mg TG-2349 (50 mg/mL in PEG 400, 4.1 mL fill), are filled into 5-mL type 1 glass syringes. Required doses during clinical study are to be dispensed using the combination of the two dose units. The entire content of the syringe is to be taken by mouth. | Drug | Panel I (TG-2349), Panel II (TG-2349), Panel III (TG-2349), Panel IV (TG-2349), Panel IX (TG-2349), Panel V (TG-2349), Panel VI (TG-2349), Panel VII (TG-2349), Panel VIII (TG-2349), Panel X (TG-2349), Panel XI (TG-2349), Panel XII (TG-2349), Panel XIII (TG-2349), Panel XIV (TG-2349), Panel XV (TG-2349), Panel XVI (TG-2349) |
| placeboAvailable in two different unit doses, 1.1 mL and 4.1 mL PEG 400 in 5-mL type 1 glass syringes. They are identical in appearance and similar in weight to TG-2349 oral liquid syringes. | Drug | Panel I (placebo), Panel II (placebo), Panel III (placebo), Panel IV (placebo), Panel IX (placebo), Panel V (placebo), Panel VI (placebo), Panel VII (placebo), Panel VIII (placebo), Panel X (placebo), Panel XI (placebo) |
Primary outcome
Pharmacokinetics (PK) profiles of single and multiple ascending oral doses of TG-2349 in healthy East Asian and Caucasian volunteers.
Time frame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Dose proportionality will be assessed by evaluating PK parameters AUC0-t, AUC0-inf, and Cmax. Parameters that are not dose dependent will be assessed by evaluating Tmax, t1/2, and λz. The linear relationship between the log-transformed PK parameter and the natural log of the dose will be tested using a linear lack-of-fit test. The dose-dependent parameters will not be dose normalized. Residual analysis will be used to assess the assumptions of normality and variance homogeneity for the statistical model.
Safety and tolerability of single and multiple ascending oral doses of TG-2349 in healthy East Asian and Caucasian volunteers.
Time frame: predose, and 2,4,6,8,12,24,48,72,96 hours post-dose
Vital signs, physical examinations, 12-lead ECG, safety laboratory parameter abnormalities, and other toxicities graded by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0 will be examined to evaluate safety profiles of the study treatments. Special attention will be paid to Grade III or IV toxicities in all treatment levels.
Pharmacokinetics (PK) profiles of multiple oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Time frame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Dose proportionality will be assessed by evaluating PK parameters AUC0-t, AUC0-inf, and Cmax. Parameters that are not dose dependent will be assessed by evaluating Tmax, t1/2, and λz. The linear relationship between the log-transformed PK parameter and the natural log of the dose will be tested using a linear lack-of-fit test. The dose-dependent parameters will not be dose normalized. Residual analysis will be used to assess the assumptions of normality and variance homogeneity for the statistical model.
Safety and tolerability of multiple ascending oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Time frame: predose, and 4,6,12 hours post-dose
Vital signs, physical examinations, 12-lead ECG, safety laboratory parameter abnormalities, and other toxicities graded by the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0 will be examined to evaluate safety profiles of the study treatments. Special attention will be paid to Grade III or IV toxicities in all treatment levels.
Antiviral activity of multiple ascending oral doses of TG-2349 in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Time frame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Descriptive statistics and graphs will be presented for the antiviral variables. Change from pre dose will be analyzed descriptively for each time point after study drug administration. Graphic displays of raw data and changes over time will be performed at each dosing level (plots of raw data of TG-2349 at each time point with mean and median). The breakthrough is defined as a greater than or equal to 1 log10 increase in HCV RNA above nadir, or detectable HCV RNA, while on treatment, after an initial drop to a level of below the detection. The slope of the plasma viral RNA decrease during the first few days of treatment, any subsequent plasma viral RNA increase observed during and/or after dosing, and all breakthrough events should be recorded and summarized.
4 secondary outcomes
The food effect of TG-2349 in healthy volunteers.
Time frame: 1 week
Appearance of viral variants if any in genotype 1, 2, 3, 4, 5, and 6 HCV-infected patients.
Time frame: during and after 3 days of TG-2349 dosing, the 4-week and 1 year follow-up periods
Ethnicity differences in safety and tolerability between East Asian and Caucasian volunteers.
Time frame: predose, and 2,4,6,8,12,24,48,72,96 hours post-dose
Ethnicity differences in Pharmacokinetics (PK) profiles between East Asian and Caucasian volunteers.
Time frame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicole Sims, DO principal investigator
WCCT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TG-2349 in people with Healthy and Hepatitis C, Chronic, run by TaiGen Biotechnology Co., Ltd. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics (PK) profiles of single and multiple ascending oral doses of TG-2349 in healthy East Asian and Caucasian volunteers. (time frame: predose, and 1,2,3,4,6,8,12,24,36,48,72,96 hours post-dose). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2014.