An open randomized parallel-comparison study of itraconazole oral solution versus itraconazole capsules in treatment of patients with oropharyngeal candidiasis

Itraconazole (ITCZ) has broad-spectrum antifungal activity and is difficult to dissolve into water. A new formulation of ITCZ, an oral solution, was recently developed. ITCZ is combined with hydroxypropyl-β-cyclodextrin (HP-β-CD), a vehicle that improves the solubility of ITCZ. This open randomized trial evaluated the clinical usefulness of ITCZ oral solution over capsules in the treatment of oropharyngeal candidiasis. ITCZ was administered orally at a dose of 200 mg a day for 7 days at 39 centers (41 clinical departments). If the subject was not cured after the 7 days of treatment and the total symptom score decreased from the baseline on Day 8, treatment was continued for an additional 7 days if necessary. ITCZ oral solution showed noninferiority to ITCZ capsules in global improvement at the primary end-point, i. e., 70.3% (52/74) for ITCZ oral solution and 49.4% (42/85) for ITCZ capsules. Global improvement at final assessments was 78.4% (58/74) for ITCZ oral solution and 68.2% (58/ 85) for ITCZ capsules. These results show that the clinical response for ITCZ oral solution is faster than that of ITCZ capsules and administering treatment for 7 days more improved the response in patients. The mycologic eradication of ITCZ oral solution versus ITCZ capsules was 71.6% (53/74) versus 32.9% (28/85) on day 8, 69.0% (20/29) versus 43.2% (19/44) on day 15. At both assessment times, the mycological efficacy of ITCZ oral solution was significantly higher (p<0.0001,p=0.006) than that of ITCZ capsules. Overall, most treatment-related adverse events were mild in both groups. All had symptoms disappear or relieved during treatment or follow-up. With ITCZ oral solution, mild gastrointestinal events are observed, but they are probably due to HP-β-CD. In conclusion, ITCZ oral solution 200 mg once daily under fasting was shown to have an early effect and good in patients with early-stage oropharyngeal candidiasi.