Page: Pre-test screening for eligible subjects was performed during the 28 days before the anticipated study start (Day 1).

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1 This document has been downloaded from subject to the terms of use state on the website. It contains data and results regarding approved and non-approved uses, formulations or treatment regimens, and it is provided for transparency and informational purposes only. The content does not reflect the complete results from all studies related to a product. As a document of scientific nature it is not to be seen as a recommendation or advice regarding the use of any products and you must always consult the specific prescribing information approved for the product prior to any prescription or use. MCB JUN-2011 Page 1 of 5 SYNOPSIS Title of trial: Skin Irritation Test of LEO Calcipotriol 50 mcg/g and Betamethasone 0.5 mg/g (as Dipropionate) Trial centre: One centre in Japan Publication (reference): No publication planned Trial period: 13-Dec-2010 (Date of first signed informed consent) to 28-Dec-2010 (Date of last study observation) Phase of development: Phase 1 Objectives: The objective of this study was to investigate skin irritation, phototoxicity, and safety of LEO (calcipotriol 50 mcg/g and betamethasone 0.5 mg/g [as dipropionate]) and its components by patch tests (48-hour closed patch test and photo patch test) in healthy Japanese male subjects. Methodology: Single centre, randomised, controlled, investigator blinded study with intra-individual comparison of the active formulation versus its components. Pre-test screening for eligible subjects was performed during the 28 days before the anticipated study start (Day 1). 1) 48-hour closed patch test On Day 1, all investigational products were applied to the left side of the back according to randomisation. Each application site was covered with an occlusive patch known as a Finn Chamber on Scanpor tape. On Day 3 (48 hours after application), the Finn Chamber was removed, and any remaining investigational products were wiped away. The skin reaction was assessed and photographed (in case of skin reaction) on Days 3 and 4. 2) Photo patch test On Day 1, all investigational products were applied to the right side of the back according to randomisation. Each application site was covered with a Finn Chamber on Scanpor tape. On Day 2, the Finn Chamber was removed, and any remaining investigational product was wiped away. One hour after removal of the investigational products, ultraviolet radiation A (UVA) (6 J/cm²) was given to the test sites. The test sites were re-covered with the Finn Chamber until Day 3. The skin reaction was assessed and photographed (in case of skin reaction) on Days 2, 3, and 4. Follow-up was applied only to adverse events (AEs) (serious or non-serious) classified as possibly or probably related to the investigational product or not assessable in relation to the investigational product that were present at the subject s last visit. These AEs were followed up as long as possible until their final outcome was determined v1.0

2 MCB JUN-2011 Page 2 of 5 Number of subjects (planned and analysed): A total of 20 healthy Japanese male subjects were to be included in the study to ensure at least 14 completers. A total of 20 subjects were enrolled and analysed. Diagnosis and main criteria for inclusion: 1. Healthy Japanese male subjects 2. Aged 20 to 40 years 3. Subjects without signs of skin irritation (erythema, dryness, roughness, or scaling) on test sites 4. Subjects willing to follow the study procedures and complete the study 5. Subjects having understood and given a written informed consent 6. Subjects without abnormal findings in physiological test and clinical test during screening who were judged to be eligible to participate in the study by the investigator Investigational product, dose and mode of administration, and batch number: All investigational products were applied once topically to the intact skin on the back at a dose of 15 mcl on Day 1. Polypropylene glycol-15 (PPG-15) was applied at a concentration of 5% in a photo patch test and at concentrations of 5% and 100% in a closed patch test. White soft paraffin and patch alone were applied as negative controls. Investigational products and their batch numbers used in this study were as follows: Investigational product Active ingredient name and concentration Batch number LEO Calcipotriol 50 mcg/g plus betamethasone 0.5 mg/g (as dipropionate) Vehicle of LEO Not applicable DAIVONEX/DOVONEX Calcipotriol 50 mcg/g Rinderon DP Betamethasone dipropionate 0.64 mg/g PPG-15 stearyl ether * 100% and 5% White soft paraffin Not applicable * The 5 % PPG-15 was prepared by the site by mixing white soft paraffin and 100% PPG-15 according to a provided procedure. Duration of treatment: The study included a pre-test screening period (up to 28 days prior to Day 1) and a 4-day testing period (Days 1 to 4). Criteria for evaluation: Efficacy: Not applicable.

3 MCB JUN-2011 Page 3 of 5 Safety: Skin reaction (skin irritation and photo-irritation) was assessed in a 48-hour closed patch test and photo patch test by dermatologists using the criteria described below. Criteria for skin irritation Definition Judgement Score No reaction 0 Only slight erythema ± 0.5 Only erythema + 1 Erythema with papules or oedema ++ 2 Erythema, oedema with papules, or oedema with vesicles Blisters Criteria for photo-irritation Observation Judgement Score No reaction or simi ar to control 0 Slightly stronger than control ± rank stronger than control ranks stronger than control ranks stronger than control ranks stronger than control If a score was 4, no further testing was performed at this test site, and skin irritation to that particular investigational product was rated as score 4 for each remaining day of the 4-day testing period. AEs, clinical laboratory measurements, physiological test results, body weight, and electrocardiogram (ECG) were recorded.

4 MCB JUN-2011 Page 4 of 5 Statistical methods: Continuous variables and variables assessed on a discrete scale were summarised using descriptive statistics including the number of values, mean, median, standard deviation (SD), and minimum and maximum values. For categorical variables, summaries included the number and percentage in each category. 1) Skin irritation index In the 48-hour closed patch test, skin irritation was assessed at each observation time point according to the criteria for skin irritation, and skin irritation index was calculated. Skin irritation index = 100 sum of clinical scores (49 to 72 hours after application) total number of scores 2) Positive ratio In the photo patch test, skin irritation and photo-irritation were assessed at each observation time point (photo-irritation was assessed only after irradiation). Each of the following positive ratios was calculated. The highest score of photo-irritation for each subject was used for the calculation. Positive ratio 1 (%) = 100 number of subjects with score 0.5 (referred to as ± ) or higher total number of subjects Positive ratio 2 (%) = 100 number of subjects with score 1 (referred to as + ) or higher total number of subjects SUMMARY CONCLUSIONS A total of 20 healthy Japanese male subjects aged 21.5 ± 1.39 years (mean age ± SD) were enrolled and completed the study. All subjects received LEO (calcipotriol 50 mcg/g and betamethasone 0.5 mg/g [as dipropionate]) and other investigational products for evaluation of the skin irritation potential and safety of LEO by the 48-hour closed patch test and photo patch test. EFFICACY RESULTS: Not applicable.

5 MCB JUN-2011 Page 5 of 5 SAFETY RESULTS: The skin irritation index for LEO90105 was very low and similar to that for the patch alone. The highest skin irritation score was 0.5 (only slight erythema) for all of the investigational products in 1 to 3 subjects except for the 100% PPG-15 stearyl ether (none of the subjects showed any skin irritation). The positive ratio for LEO was 0% in all subjects. No AEs, SAEs, or significant laboratory findings were observed in this study. Investigational product N Skin irritation index in 48-hour closed patch test Mean (SD) Positive ratio in photo patch test Number of Positive ratio * subjects * (%) LEO (7.69) Vehicle of LEO (5.59) DAIVONEX/DOVONEX (9.16) Rinderon DP (5.59) % PPG-15 stearyl ether (5.59) % PPG-15 stearyl ether or (0.0) white soft paraffin ** White soft paraffin (5.59) Patch alone (7.69) * The highest score of photo-irritation for each subject is 0.5 (referred to ± ) or higher. ** 100% PPG-15 stearyl ether was applied for the 48-hour closed patch test, whereas white soft paraffin was applied to the symmetrical site for the photo patch test. Source: Table and Table CONCLUSION: No skin irritation or phototoxicity was observed in any healthy Japanese male subjects who received LEO in the patch tests conducted for this study. No safety issues arose during the 4-day testing period. Date of the Report: 02-Jun-2011