Eight US centers enrolled in a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial comparing the efficacy of 12, 16, and 24 weeks of oral therapy with terbinafine, 250 mg/day, and placebo in patients aged 18 to 75 years with both a positive KOH wet mount and mycologic culture of one or more dermatophytes from the large toenail, designated as the target toenail, or another infected toenail if no large toenail was infected. Primary exclusion criteria included: systemic antifungal therapy during the previous 3 months; topical antifungal therapy for the infected toenail(s) during the previous month; white superficial toenail onychomycosis; immunosuppression or immunodeficiency, including known human immunodeficiency virus (HIV) infection; hepatic enzymes >1.5 times the upper limit of normal at screening; and any marked laboratory abnormalities.
Patients were randomized into four treatment groups: (i) 12 weeks of terbinafine (250 mg/day) followed by 12 weeks of placebo; (ii) 16 weeks of terbinafine followed by 8 weeks of placebo; (iii) 24 weeks of terbinafine; and (iv) 24 weeks of placebo. Both patient and physician were blinded to the treatment for the 24-week treatment period. Blinding was maintained through the end of the study. Assessments were done at week −6 (screening visit) and at weeks 4, 8, 12, 16, 20, and 24 during the treatment period. Follow-up assessments were scheduled for weeks 30, 36, 42, 48, 60, and 72. The mycologic efficacy variables included the percentage of patients with negative mycologic cultures, with negative KOH wet mounts, and with mycologic cure (both negative culture and negative KOH). The evaluations at week 48 and week 72 are reported here. The primary clinical variable was clinical cure, defined as 0% involvement of the target toenail.
The efficacy analysis included all patient who were randomized to therapy, fulfilled the mycologic criteria at screening, took at least one dose of study drug, and had at least one post-baseline assessment. For each variable, the percentage in each treatment group showing efficacy was compared with the percentage in the corresponding placebo group.