Investigational
HCV Inhibitor TMC435 Demonstrates Promising Safety and Efficacy
in Phase 1 Study
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| SUMMARY:
Tibotec's investigational hepatitis C virus (HCV) NS3/4A
protease inhibitor TMC435
demonstrated good antiviral activity and appeared to
be safe and generally well-tolerated in a Phase 1 placebo-controlled
clinical trial, according to a report in the March
2010 Gastroenterology. |
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By
Liz Highleyman
As the first of the directly-targeted oral anti-HCV drugs near
the end of the drug development pipeline, researchers continue
to test a variety of novel agents.
Henk Reesink from the Academic Medical Center in Amsterdam and
colleagues recently published data from the first-in-humans Phase
1 clinical trial (dubbed TMC435350-C101) to evaluate the safety,
tolerability, and pharmacokinetics of TMC435.
In the first part of the study, 49 healthy HCV negative volunteers
were randomly assigned to receive TMC435 as single ascending doses
(up to 600 mg) or multiple ascending doses (100, 200, or 400 mg
once-daily or 200 mg twice-daily) over 5 days, or else placebo.
Then, in the open-label second part of the study, 6 patients with
hard-to-treat HCV genotype 1 received 200 mg TMC435 once-daily
for 5 days to assess antiviral activity.
Results
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There
were no serious adverse events, grade 3 reactions, or treatment-related
discontinuations reported during either part of the study. |
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The
pharmacokinetic profile of TMC435 was suitable for a once-daily
dosing regimen. |
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Among
the participants with hepatitis C, plasma HCV viral load levels
decreased rapidly in all patients. |
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An
initial steep decline in HCV RNA (median 3.5 log10 IU/mL at
day 3) was followed by a more gradual decline that was maintained
over the dosing period. |
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The
median maximal HCV RNA reduction was 3.9 log10 IU/mL, occurring
after a median 6 days. |
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No
instances of viral breakthrough (>1 log10 IU/mL HCV RNA
increase from the nadir or lowest level) were observed during
treatment or the first 3 days post-treatment. |
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After
completing treatment, HCV viral load levels returned to pre-treatment
levels by week 4 of follow-up. |
Based
on these findings, the investigators concluded, "Once-daily
TMC435 given orally was generally safe and well tolerated, and
demonstrated potent antiviral activity."
Academic Medical Center, Amsterdam, Netherlands; Tibotec Pharmaceuticals
Ltd, Eastgate Village, Little Island, Cork, Ireland; PRA International
EDS, Zuidlaren, Netherlands.
4/2/10
Reference
HW
Reesink, GC Fanning, K Abou Farha, and others. Rapid HCV-RNA decline
with once-daily TMC435: A Phase I study in healthy volunteers
and hepatitis C patients. Gastroenterology 138(3): 913-921
(Abstract).
March 2010.
