Oral pleconaril treatment of picornavirus-associated viral respiratory illness in adults: efficacy and tolerability in phase II clinical trials.

We evaluated the efficacy and tolerability of oral pleconaril, an anti-picornavirus agent, in treating acute viral respiratory illness (VRI) in two double-blind, placebo-controlled trials. Otherwise healthy subjects, 14 years of age or older, who presented within 36 h of VRI symptom onset, were randomized to pleconaril 400 mg or matching placebo in liquid (first trial) or tablet (second trial) formulations twice-daily (first trial only) or three-times daily for 7 days. The infected subjects from the corresponding active and placebo groups (three-times daily dosing regimens) were combined for analysis. Among the subset of subjects with proven picornaviral infection in both studies (42% of total enrolled), pleconaril 400 mg three-times daily (n = 323) reduced the time to alleviation of illness (no rhinorrhoea and other symptoms mild or absent for > or = 48 h) compared with placebo (n = 264) (median: 10.0 days for placebo and 8.5 days for pleconaril; P = 0.029). In addition, pleconaril reduced the time to a > or = 50% reduction from baseline in total symptom severity score (median: 4.5 days for placebo and 3.5 days for pleconaril; P = 0.038). Significant reductions in the number of tissues used for nose-blowing (20% reduction) and in nights of disturbed sleep (16% reduction) were also observed. Pleconaril was generally well tolerated; the liquid formulation caused gastrointestinal disturbance in all groups (diarrhoea 10-14%, nausea 5-9%, abdominal discomfort 6-8%), and tablets were associated with a greater incidence of nausea (3% for placebo versus 7% for pleconaril, P = 0.003). Pleconaril 400 mg administered three-times daily reduced the duration and severity of picornaviral VRI in adolescents and adults.