Primary : to investigate the safety, tolerability and antiviral activity of multiple oral doses of JTK-652 administered for 4 weeks in subjects with chronic hepatitis C infection (genotype 1a, 1b)Secondary : to investigate the pharmacokinetics of…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety : AEs, clinical laboratory parameters, vital signs, ECG and physical
examination
Pharmacokinetics : plasma JTK-652 concentrations, pharmacokinetic parameters
(Cmax, Ctrough, tmax, AUC0-*, Rac
Secondary outcome
Efficacy : HCV RNA reduction (log10 copies/mL) from baseline at Week 4 and
percent change and change from baseline in ALAT reduction (IU/L) at Week 4
Background summary
Hepatitis C results from infection with the hepatitis C virus (HCV) through
exposure to infected blood. When infected with HCV, the disease usually
progresses asymptomatically, although malaise followed by anorexia, nausea,
vomiting or jaundice may develop in some cases. Fifty-five to 85% of
HCV-infected patients become persistent HCV-infected patients (HCV carriers),
and chronic hepatitis develops in 65% to 70% of the HCV carriers. The most
important sequelae of chronic HCV infection are progressive liver fibrosis
leading to cirrhosis and hepatocellular carcinoma. If HCV carrier individuals
aged 40 years remain untreated until 70 years old, it is expected that 20 to
25% of them will develop hepatocellular carcinoma. The number of HCV carriers
is estimated to be 170 million worldwide and 2 million in Japan1, and that of
newly infected patients is estimated to be 3 to 4 million worldwide per year.2
In the treatment of hepatitis C, the standard therapy is the treatment with
interferon (IFN), either alone or in combination with ribavirin (RBV). IFNs
used for the treatment include standard IFN and IFN modified with polyethylene
glycol (pegylated-IFN; PEG-IFN), which is used in a once-a week dosing regimen
due to prolonged half-life in blood. At present, the first-line drug is PEG IFN
because of lower frequency of dosing and better safety and efficacy. The most
effective treatment is a combination with PEG-IFN and RBV. Basically, all
patients with chronic hepatitis C are subject to the treatment, however, the
aggressive treatment is recommended particularly for patients with an increased
risk of developing liver cirrhosis.
JTK-652 shows potent inhibitory activity against the HCV pseudo typed virus
infection. Thus, an anti-HCV effect is expected when JTK-652 is administered
alone or in combination with IFN. The mechanism of action of JTK-652 is quite
different from that of the NS3 protease inhibitor or the NS5B RNA polymerase
inhibitor that have been intensively developed by the other pharmaceutical
companies. Therefore, additive or synergy anti-HCV effect is also expected when
JTK-652 is administered in combination with these inhibitors. In addition, it
is expected that JTK-652 will exert anti-HCV activity against drug-resistant
viruses.
Study objective
Primary : to investigate the safety, tolerability and antiviral activity of
multiple oral doses of JTK-652 administered for 4 weeks in subjects with
chronic hepatitis C infection (genotype 1a, 1b)
Secondary : to investigate the pharmacokinetics of multiple oral doses of
JTK-652 in subjects with chronic hepatitis C infection (genotype 1a, 1b)
Study design
a randomized, double-blind, placebo-controlled study in subjects with chronic
hepatitis C infection enrolled into two multiple dose cohorts (JTK-652 400 mg
and 800 mg). In each cohort, ten subjects (8 active and 2 placebo) will be
randomized to receive JTK-652 or placebo every 8 hours for 4 weeks.
Intervention
JTK-652
Study burden and risks
JTK-652:
As JTK-652 is currently administered to man for the first time in studies with
healthy volunteers, adverse effects in man have not been reported by date of
this report. In previous studies with rats and dogs in which JTK-652 was
administered daily in (very) high doses over a period of 1 month, the following
adverse effects were observed: vomiting, abnormal faeces (whitish and soft
stool, or diarrhoea), slightly increased liver enzymes and fat change in
specific liver cells, hypertrophy of sinusoidal cells in liver (increase in
size of a specific type of liver cells not associated with changes in liver
enzyme function), slight prolonged blood coagulation time not associated with
changes in bleeding, mild increase in thyroid weight and increase in size of
typical cells in the thyroid gland. At very high doses sensitivity for sun
light was found.
Procedures:
pain, a bruise from the canula. Light bleeding and possibly an infection from
blood collection
JT BLdg. 2-1, Toranomon 2-chrome
Minato-ky, Tokyo, 105-8422
Japan
JT BLdg. 2-1, Toranomon 2-chrome
Minato-ky, Tokyo, 105-8422
Japan
Listed location countries
Age
Inclusion criteria
Age : 18-65 yr, inclusive
BMI : 18.5-32 kg/m2, inclusive
Subjects : males and postmenopausal females with
- chronic hepatitis C infection (genotype 1a or 1b, or mixed 1a/1b)
- HCV-RNA * 100 KIU/mL
- ALAT * 5 times of upper limit of normal (ULN
Exclusion criteria
1. Evidence of human immunodeficiency virus (HIV) infection (enzyme immunoassay confirmed by Western blot)
2. Evidence of chronic hepatitis B virus (HBV) infection (HB surface antigen [HBsAg])
3. Evidence of acute hepatitis A infection (hepatitis A IgM+)
4. Antiviral therapy for HCV within preceding 6 months (including all types of interferon, ie, standard, pegylated)
5. Systemic antiviral, cytotoxic, hepatotoxic, or immunomodulatory therapy within 3 months prior to first dose
6. Recent (* 3 months prior to screening) history of alcohol or drug abuse
7. Evidence of Child-Pugh B or C liver disease (for Child-Pugh classification see Appendix 9.7)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-005093-31-NL |
| CCMO | NL19812.056.07 |