Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials

Abstract

The novel capsid-binding antiviral pleconaril inhibits in vitro replication of most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2 parallel randomized, double-blind, placebo-controlled trials. Among 1363 picornavirus-infected participants (65%) in the studies combined, the median time to alleviation of illness was 1 day shorter for pleconaril recipients than for placebo recipients (P<.001). Cold symptom scores and frequency of picornavirus cultured from nasal mucus specimens were lower among pleconaril recipients by day 2 of treatment. No treatment effects were seen in those without picornavirus infection. Pleconaril was associated with a higher incidence of nausea (6% vs. 4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol levels and platelet counts, compared with baseline measurements. A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol. Early pleconaril treatment was well tolerated and significantly reduced the duration and severity of colds due to picornaviruses in adults.

Figure 1

Kaplan-Meier analyses of time to alleviation of illness (primary efficacy end point) among picornavirus-infected subjects. Marks on the x axis represent end of study day.

Figure 2

Change from baseline value in total cold symptom severity scores among picornavirus-infected subjects, days 1–6. Pleconaril recipients experienced significant (P > .05) reductions from baseline by day 2 of treatment in each study.

Figure 3

Antiviral activity in studies 843-043 and 843-044 combined: change in viral RNA levels from baseline values, as determined using the RT-PCR TaqMan assay (Applied Biosystems; numbers in parentheses are median virus levels at each time point in relative plaque-forming units per milliliter derived from the HRV1B standard curve) and results of viral cultures for subjects with positive culture results at baseline.