SHORT-TERM ITRACONAZOLE VERSUS TERBINAFINE IN THE TREATMENT OF TINEA-PEDIS OR MANUS

A total of 304 patients with a clinical diagnosis of palmar-type tinea pedis or manus and a positive mycologic examination were recruited in to this double-blind, randomized, multicenter, phase III study. Patien ts were randomized to receive either oral itraconazole 200 mg twice da ily (in the morning and evening) for 7 days, followed by placebo for 7 days (n = 153), or placebo in the morning and oral terbinafine 250 mg in the evening for 14 days (n = 151). At the first visit and 1, 2, an d 6 weeks after the start of the study, signs and symptoms were assess ed clinically, and scales were taken for mycologic assessments (micros copy and culture). At weeks 1, 2, and 6, the effectiveness of therapy was evaluated globally and given a rating of healed (absence of signs and symptoms), marked improvement (greater than or equal to 50% clinic al improvement), considerable residual lesions (< 50% clinical improve ment), no change, or worsened. The primary efficacy parameter was the mycologic cure rate at the follow-up end-point (week 6). The tolerabil ity of the study medications was assessed at weeks 1 and 2, Adverse ev ents were recorded at weeks 1, 2, and 6. Routine hematologic and bioch emical tests were performed at the start of the study and after 1 week of treatment. No significant differences were seen in the baseline pa tient characteristics between the two groups. The rate of mycologic cu re (negative microscopy and culture test result) was 79% in the itraco nazole group and 80% in the terbinafine group at the follow-up end-poi nt, The analysis of the 90% confidence interval for the difference bet ween the treatment groups (-7.1, 5.4) and the outcome of the Blackweld er test (for two one-sided tests, P = 0.013 and P = 0.029) showed the two treatments to be equivalent. The results of the global evaluations of the efficacy in the two treatment groups are shown in Table 1. The rate of clinical response (healed or markedly improved) was 93% in th e itraconazole group and 91% in the terbinafine group at the follow-up end-point. The analysis of the 90% confidence interval for the differ ence between the two groups (-2.5, 5.7) and the outcome of the Blackwe lder test (for two one-sided tests, P = 0.004 and P < 0.001) showed th e two treatments to be equivalent. The severity of the clinical signs and symptoms decreased from the baseline to the treatment end-point an d from the treatment end-point to the follow-up end-point in both grou ps. At the double-blind treatment period end-point (week 2), the toler ability of the study medication was rated as very good or good in more than 97% of patients. During treatment, 21 of 153 patients (14%) in t he itraconazole group and 28 of 151 patients (19%) in the terbinafine group reported adverse events. During follow-up, one patient in the it raconazole group and two in the terbinafine group reported adverse eve nts. The most frequent events were headache, abdominal pain, nausea, v omiting, and hypertriglyceridemia. Two patients in the itraconazole gr oup and four in the terbinafine group withdrew because of adverse even ts. Severe adverse events were reported by one patient in the itracona zole group and five in the terbinafine group. Serious adverse events w ere reported by two patients in the terbinafine group, although these were probably not drug related. No clinically relevant changes in labo ratory variables were observed.