Randomized, placebo-controlled, phase 3 study of itraconazole for the treatment of onychomycosis.

BACKGROUND: Itraconazole, approved for treatment of toenail fungal infection onychomycosis, provides antifungal activity at a dosage requiring once-daily (QD) administration of 2 100-mg capsules for 12 weeks. Utilizing the Meltrex® technology delivery system, a novel 200-mg formulation of itraconazole was developed delivering the same dosage as 2 capsules in a single tablet. METHODS: This phase 3, randomized, placebo-controlled trial investigated the noninferiority of 1 itraconazole 200-mg tablet to 2 itraconazole 100-mg capsules dosed QD for 12 weeks, with a 40-week follow-up period. Clinical Cure (Investigator's Global Assessment plus mycological examination) was the primary outcome measure and Clinical Improvement was a secondary endpoint. Safety and efficacy of itraconazole 200-mg tablets were also compared with placebo. RESULTS: Significantly more patients in the intent-to-treat per-protocol populations on itraconazole (200-mg tablet or 2 100-mg capsules) achieved Complete Cure and Clinical Improvement compared with placebo. For both endpoints, itraconazole 200-mg tablet QD was noninferior to itraconazole 100-mg capsules and superior to placebo. All treatment groups demonstrated a similar safety profile with no new safety signals identified. LIMITATIONS: Absolute patient blinding was not possible; the number of tablets versus capsules differed, and the appearance of the active drugs could not be masked. However, efficacy was based on objective assessments from blinded investigators. CONCLUSIONS: Once-daily itraconazole 200-mg was well-tolerated, and may be an effective alternative to 2 itraconazole 100-mg capsules for the treatment of toenail onychomycosis. The convenience of a simpler dosing regimen may improve patient compliance

Adapalene gel 0.3% for the treatment of acne vulgaris: a multicenter, randomized, double-blind, controlled, phase III trial.

BACKGROUND: A new 0.3% gel formulation of adapalene has been developed. OBJECTIVE: We sought to provide evidence of the superiority of adapalene gel 0.3% over adapalene gel 0.1% and gel vehicle in the treatment of acne. METHODS: A total of 653 patients were randomized to receive adapalene gel 0.3%, adapalene gel 0.1%, or vehicle once daily for 12 weeks (2:2:1 randomization). Analysis for efficacy was conducted on correlated repeated measurements at weeks 8 and 12 using Generalized Estimating Equation methodology. RESULTS: Adapalene gel 0.3% was significantly superior to adapalene gel 0.1% and vehicle in success rate, total lesion count, and inflammatory lesion count. A consistent, dose-dependent effect was demonstrated for all efficacy measures. Signs and symptoms were mostly mild to moderate and transient in nature. LIMITATIONS: Adjunctive topical or oral agents and their impact on acne were not studied in this trial. CONCLUSIONS: Adapalene gel 0.3% was effective and well tolerated in the treatment of acne.