Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis.

BACKGROUND: There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. OBJECTIVE: Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. METHODS: Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. RESULTS: All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. LIMITATIONS: Local skin responses may have suggested active treatment to investigators. CONCLUSIONS: Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

Efficacy and safety of a new once-daily topical ketoconazole 2% gel in the treatment of seborrheic dermatitis: a phase III trial.

BACKGROUND: The first gel formulation of ketoconazole has been tested in 2-week treatment courses. OBJECTIVE: To evaluate the efficacy and safety of a new, once-daily, 2-week ketoconazole 2% gel treatment in moderate to severe seborrheic dermatitis. METHODS: Four hundred fifty-nine subjects with moderate to severe seborrheic dermatitis were randomized to receive ketoconazole 2% gel or vehicle gel once daily for 14 days. The primary efficacy was the proportion of successfully treated subjects at day 28 (cleared and almost cleared). RESULTS: A significantly greater percentage of subjects were successfully treated with ketoconazole 2% gel compared with vehicle (25.3% vs. 13.9%, P = .0014). Ketoconazole 2% gel improved erythema, scaling (P = .0022 vs. vehicle), and pruritus. Mean overall symptom severity was reduced by 53% and 39% with ketoconazole gel and vehicle, respectively. Adverse events were few, generally mild or moderate, and similar between treatment groups. CONCLUSION: Once-daily ketoconazole 2% gel is an effective,well-tolerated, convenient, and cosmetically acceptable treatment for moderate to severe seborrheic dermatitis.

Randomized, double-blind, placebo-controlled study evaluating the lidocaine/tetracaine patch for induction of local anesthesia prior to minor dermatologic procedures in geriatric patients.

BACKGROUND: Topical anesthetics offer a noninvasive method of anesthesia. OBJECTIVE: To evaluate the efficacy and safety of the lidocaine/tetracaine patch, a 1:1 (wt:wt) eutectic mixture of lidocaine and tetracaine, for local anesthesia before minor dermatologic procedures in geriatric patients. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study, 79 patients over the age of 65 years received a 30-minute application of either the lidocaine/tetracaine patch or placebo immediately before a shave biopsy or superficial excision. The primary measure of efficacy was patient assessment of procedural pain using the visual analog scale (VAS). Secondary efficacy end points included patient, investigator, and independent observer assessments. RESULTS: There was a statistically significant difference (p = .041) in patient ratings of pain by VAS score in the active group (9.5 mm) compared with the placebo group (22.5 mm). None of the secondary end points showed a statistically significant difference between groups. No adverse events were reported. CONCLUSION: The lidocaine/tetracaine patch is a safe and effective method for noninvasive induction of local anesthesia for minor dermatologic procedures in patients over the age of 65 years.

Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials.

OBJECTIVE: To determine the safety and efficacy of photodynamic therapy (PDT) using 20% wt/vol aminolevulinic acid hydrochloride (hereinafter "ALA") and visible blue light for the treatment of multiple actinic keratoses of the face and scalp. DESIGN: Randomized, placebo-controlled, uneven parallel-group study. INTERVENTIONS: Patients (N = 243) were randomized to receive vehicle or ALA followed within 14 to 18 hours by PDT. Follow-up visits occurred 24 hours and 1, 4, 8, and 12 weeks following PDT. Target lesions remaining at week 8 were re-treated. MAIN OUTCOME MEASURE: Clinical response based on lesion clearing by week 8. RESULTS: Most patients in both groups had 4 to 7 lesions. Complete response rates for patients with 75% or more of the treated lesions clearing at weeks 8 and 12 were 77% (128/166) and 89% (133/149), respectively, for the drug group and 18% (10/55) and 13% (7/52), respectively, for the vehicle group (P<.001, Cochran-Mantel-Haenszel general association test). The 95% confidence interval for the difference in response rates at week 8 was 46.9% to 71.0% and at week 12, 65.3% to 86.3%. The week 12 response rate includes 30% of patients who received a second treatment. Most patients experienced erythema and edema at the treated sites, which resolved or improved within 1 to 4 weeks after therapy, and stinging or burning during light treatment, which decreased or resolved by 24 hours after light treatment. CONCLUSION: Findings indicate that topical ALA PDT is an effective and safe treatment for multiple actinic keratoses of the face and scalp.