Affiliation:
1. Department of Internal Medicine
2. Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908
3. Agouron Pharmaceuticals, Inc., Pfizer Company, San Diego, California 92121
Abstract
ABSTRACT
Human
rhinovirus (HRV) infections are usually self-limited but may be
associated with serious consequences, particularly in those with asthma
and chronic respiratory disease. Effective antiviral agents
are needed for preventing and treating HRV illnesses. Ruprintrivir
(Agouron Pharmaceuticals, Inc., San Diego, Calif.) selectively inhibits
HRV 3C protease and shows potent, broad-spectrum anti-HRV activity in
vitro. We conducted three double-blind, placebo-controlled clinical
trials in 202 healthy volunteers to assess the activity of ruprintrivir
in experimental HRV infection. Subjects were randomized to receive
intranasal ruprintrivir (8 mg) or placebo sprays as prophylaxis (two or
five times daily [2×/day or 5×/day] for 5
days) starting 6 h before infection or as treatment
(5×/day for 4 days) starting 24 h after infection.
Ruprintrivir prophylaxis reduced the proportion of subjects with
positive viral cultures (for 5×/day dosing groups, 44%
for ruprintrivir treatment group versus 70% for placebo
treatment group [
P
= 0.03]; for
2×/day dosing groups, 60% for ruprintrivir group versus
92% for placebo group [
P
= 0.004])
and viral titers but did not decrease the frequency of colds.
Ruprintrivir treatment reduced the mean total daily symptom score (2.2
for ruprintrivir treatment group and 3.3 for the placebo treatment
group [
P
= 0.014]) by 33%. Secondary
endpoints, including viral titers, individual symptom scores, and nasal
discharge weights, were also reduced by ruprintrivir treatment.
Overall, ruprintrivir was well tolerated; blood-tinged mucus and nasal
passage irritation were the most common adverse effects reported.
Pharmacokinetic analysis of plasma and nasal ruprintrivir
concentrations revealed intranasal drug residence with minimal systemic
absorption. Results from these studies in experimental rhinoviral
infection support continued investigation of intranasal ruprintrivir in
the setting of natural HRV
infection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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