Clinical Trial Result Information

Protocol number
ML18349

Title of Study
Open label, multicenter, study evaluating the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis in pediatric patients.

Sponsor
Produtos Roche Químicos e Farmacêuticos S.A.

Company division
Pharmaceutical

Product name
Protopic

Generic name
tacrolimus ointment

Therapeutic area
Atopic Dermatitis

Clinical study summary
This was an open label, non-randomized, single group study to evaluate the efficacy and safety of tacrolimus ointment in children, aged 2 to 10, with atopic dermatitis.

Study center(s)
9 centers in Brazil.

Phase of development
III

Objectives
Evaluate the efficacy and safety of tacrolimus ointment 0.03% in treating the signs and symptoms of atopic dermatitis in pediatric subjects.

Methodology
Pediatric patients with mild to severe atopic dermatitis were treated twice daily for 6 weeks with tacrolimus ointment, administered topically. Two weeks post-treatment, the affected area was assessed in terms of clinical response, percentage of body surface area affected, and the area and severity of eczema.

Number of patients (planned/analyzed)
174 enrolled.

Diagnosis and main criteria for inclusion
Pediatric patients aged 2-10 years, with a clinical diagnosis of mild, moderate or severe atopic dermatitis.

Test product, dose and mode of administration or test procedure
Protopic (tacrolimus) ointment, 0.03%, applied as a thin layer over areas affected with atopic dermatitis, twice daily.

Duration of treatment
6 weeks.

Reference therapy, dose and mode of administration or reference procedure
N/A

Criteria for evaluation (efficacy, safety)
Efficacy: Primary: Incidence of success based on the physician's global evaluation of clinical response. Success was defined as a rating of cleared or excellent improvement (i.e. at least 90% improvement in the areas defined for treatment at baseline) at the end of treatment.
Secondary: The percent of body surface area affected (% BSA); the eczema area and severity index (EASI); the patient's assessment of pruritus.

Safety: Adverse events and serious adverse events, as reported by the patient and the Investigator.

Statistical methods
A success rate of 37.8% was assumed for tacrolimus ointment 0.03% in the pediatric population, giving a calculated sample size of 155 patients, with an estimated success rate ranging from 30.3% to 45.3%. Considering a possible 10% 'dropout' a sample size of 170 patients was chosen.
All patients who used the study medication and who had at least one efficacy or safety evaluation after baseline were included in the ITT (intention to treat) population.

Summary (efficacy, safety, other results)
Global Assessment: Week 1 to Week 6 – ITT population

The primary parameter (excellent improvement or cleared by end of treatment) was achieved. There was a 37% success rate at 3 weeks, and by the end of treatment 56% of patients had a rating of ‘cleared’ or ‘excellent improvement.’
Secondary parameters: In the Eczema Area and Severity Index (EASI) a statistically significant variation was found between the average scores for weeks 0, 1, 3 and 6 (p<0.001), and between each week’s score compared to baseline (p<0.001). Average reductions in EASI score at weeks 1, 3 and 6 compared to baseline were 45.5%, 58.3% and 61.8% respectively.
In the Body Surface Area (BSA) evaluation a statistically significant variation was found between the average scores for weeks 0, 1, 3 and 6 (p<0.001) and between each week’s score compared to baseline (p<0.001). Average reductions in BSA score at weeks 1, 3 and 6 compared to baseline were 30.4%, 47.5% and 55.5% respectively.
The patients’ evaluation of a burning sensation was measured on a visual analogue scale.
In this evaluation, a statistically significant variation was seen between the average scores for weeks 0, 1, 3 and 6 (p<0.001) and between each week’s score compared to baseline (p<0.001). Average reductions in burning evaluation marks at weeks 1, 3 and 6 compared to baseline were 2.2, 2.6 and 2.7 respectively.

Safety: The majority of adverse events recorded in this study were considered unrelated to treatment; the most common adverse events were fever (37.6%), burning (25.3%), pyodermitis (18.2%) and pruritus (12.9%). Of the 98/349 adverse events considered related to treatment, the most common were burning (17.0%), pruritus (9.4%) and pyodermitis (6.5%).
Five patients experienced serious adverse events; four of these SAEs (asthma x 2, bronchopneumonia and pyodermitis) were considered unrelated to treatment, but resulted in premature discontinuation from the study. The fifth, periocular abscess, was considered related to treatment; it was treated successfully with antibiotics, and did not result in premature discontinuation from the study.

Conclusions
The results of this study indicate that tacrolimus ointment 0.03% is a rapid onset, safe and effective non-steroidal topical therapy for the treatment of mild to severe atopic dermatitis in pediatric patients.

Date of report
2/1/2007

Click here for the protocol registry listing of this trial.