Clinical Study Report Synopsis

Transcription

1 Clinical Study Report Synopsis Skin Irritation Test of LEO gel (calcipotriol hydrate plus betamethasone dipropionate) in healthy Japanese subjects Design of trial: A phase 1, national, single-centre, prospective, randomised, controlled, single application, investigator-blinded trial of LEO gel (calcipotriol hydrate 52.2 μg/g [equivalent to 50.0 μg/g calcipotriol] plus betamethasone dipropionate mg/g), vehicle of LEO gel and Liquid Paraffin The clinical trial, including the archival of essential documents, was conducted in compliance with the clinical trial protocol, GCP, and the applicable regulatory requirement(s). LEO Pharma A/S Trial ID: LP Date: 04-Apr-2016 Version: Final

2 Trial ID: LP Apr-2016 Page 2 of 5 Clinical Trial Report Synopsis Statement Approval Statement, LEO Pharma A/S The following persons have approved this clinical study report synopsis using electronic signatures as presented on the last page of this document:, MSc Stat, Global Clinical Operations, MD Medical Department Approval Statement, International Coordinating Investigator The international coordinating investigator approves the clinical study report synopsis by manually signing the International Coordinating Investigator Clinical Study Report Approval Form, which is a separate document adjoined to the clinical study report. The following person has approved this clinical study report synopsis:, MD, PhD International Coordinating Investigator

3 Trial ID: LP Apr-2016 Page 3 of 5 Trial Registration Number NCT EudraCT number N/A Title of Trial Skin Irritation Test of LEO gel (calcipotriol hydrate plus betamethasone dipropionate) in healthy Japanese subjects Investigators investigator MD., PhD, Trial Centres This trial was conducted at one centre in Japan. Publications None at the time of the final Clinical Study Report. Clinical Trial Period Date of first subject first visit: 02-Mar-2015 Date of last subject last visit: 11-Apr-2015, Japan, was appointed as signatory Development Phase Phase 1 Objectives The primary objective was to investigate skin irritation and photo-irritation of LEO gel, gel vehicle and Liquid Paraffin in healthy Japanese men. The secondary objective was to investigate the safety of LEO gel, gel vehicle and Liquid Paraffin in healthy Japanese men. Methodology A phase 1, national, single-centre, prospective, randomised, controlled, single application, investigator-blinded trial of LEO gel (calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate mg/g), vehicle of LEO gel and Liquid Paraffin. Closed Patch test On Days 3 and 4, 49 and 72 hours, respectively, after application of the Finn chambers, irritation was assessed on each test site on a 6-point scale: 0, 0.5, 1, 2, 3, 4. Photo Patch test On Day 2, 25 hours after application of the chambers, irritation was assessed on each test site using the same scale as above. Test sites were exposed to UVA light for 7.5 minutes, and the irritation assessment was repeated. On Days 3 and 4, 49 and 72 hours after the application of the chambers, respectively, irritation assessment was repeated on each test site. Number of Subjects Planned and Analysed Twenty subjects were planned to be randomised, and 20 subjects were randomised and analysed. Diagnosis and Main Criteria for Inclusion Healthy Japanese men aged 20 to 40 years inclusive, without signs of skin irritation/disease/disorders/symptoms or blemishes on test sites. Test Product, Dose and Mode of Administration, Batch Number LEO gel applied once to each subject s back on two sites. Each application was of 15 µl and under separate Finn chambers. Batch number Duration of Treatment Single application. Reference Product, Dose and Mode of Administration, Batch Number Vehicle of LEO gel applied once to each subject s back on two sites. Each application was of 15 µl and under separate Finn chambers. Batch number Liquid paraffin applied once to each subject s back on two sites. Each application was of 15 µl and under separate Finn chambers. Batch number E Empty Finn chamber applied once to each subject s back on two sites.

4 Trial ID: LP Apr-2016 Page 4 of 5 Trial Endpoints Multiple primary endpoints derived from the skin irritation assessment at the test sites were defined for this trial. Skin irritation endpoint From the assessments of skin irritation at the Closed Patch test sites, the skin irritation index was calculated as the sum of the scores from Days 3 and 4 divided by the total number of assessments and multiplied by 100. Photo irritation endpoints On Day 2, the irritation assessment for a Photo Patch test site after UV exposure was compared with the irritation assessment at the same site before UV exposure, and the irritation increase defined the following two photo-irritation endpoints: a)the event that the test site increased in irritation after UV exposure b)the event that the test site increased at least one rank in irritation after UV exposure In a similar manner, two events for each of Day 3 and Day 4 were defined, i.e. an increase in irritation after UV exposure and an increase of at least one rank in irritation after UV exposure. However, for these the comparison of the irritation assessment for the Photo Patch test site was towards the irritation assessment from the corresponding Closed Patch test site, i.e. comparisons were between test sites treated in the same way but with and without UV exposure Adverse events, laboratory tests, ECG, vital signs, physical findings and weight were also evaluated in this trial. Statistical Methods Skin irritation From the Closed Patch test sites, descriptive statistics of the skin irritation index and of the scores of irritation on Day 3 and Day 4 are presented by treatment. Photo-irritation From the photo-irritation scores the following two positive ratios are calculated and presented: Number of subjects with an increase in irritation after UV exposure divided by total number of subjects and multiplied by 100. Number of subjects with an increase of at least one rank in irritation after UV exposure divided by total number of subjects and multiplied by 100.

5 Trial ID: LP Apr-2016 Page 5 of 5 Summary of Results Trial Population A total of 20 healthy Japanese men aged 22±3 years (mean age ± SD) were randomised and completed the trial. All subjects received the three investigational products and an empty chamber for Closed Patch test and Photo Patch test. Efficacy Results Not applicable. Safety Results Of the 20 subjects in the Safety Analysis Set, one subject (5.0%) only experienced a treatment-emergent adverse event (TEAE), which was a mild erythema, occurring on/around an empty chamber site and considered related to treatment (this was assessed before the blind was broken). There were no other TEAEs. No skin irritation or photo-toxicity was observed for LEO gel or vehicle of LEO gel in the Closed Patch test and Photo Patch test. No safety issues related to LEO gel or vehicle of LEO gel were observed when applied to healthy Japanese men. Closed Patch test Skin irritation index* LEO gel Vehicle of LEO gel Liquid Paraffin Empty Chamber N=20 N=20 N=20 N=20 n (%) n (%) n (%) n (%) Mean (SD) 0 (0.00) 0 (0.00) 1.3 (5.59) 3.8 (12.23) Photo Patch test Increase in irritation after UV exposure Number of subjects Positive ratio (%)** Increase of at least one rank in irritation after UV exposure Number of subjects Positive ratio (%)*** *: Skin irritation index: 100 summation of clinical score / Total number of assessments. **: Positive ratio (%) = 100 (Number of subjects with any increase in irritation / Total number of subjects) ***: Positive ratio (%) = 100 (Number of subjects with increase in irritation of at least one rank / Total number of subjects) Conclusion No safety issues, including skin irritation and photo-toxicity, were observed for LEO gel or vehicle of LEO gel in this trial conducted in 20 healthy Japanese men.

6 LP Clinical Study Report Synopsis 04-Apr English ELECTRONIC SIGNATURES Electronic signahtre made within edoc LEO by LEO Pharma AIS employees or employees of any LEO Pharma AIS affiliate located anywhere in the world, are to be considered to be legally binding equivalent of traditional handwritten signahtres. Biostatistical 08-Apr :32 GMT+02 - Department, Medical Approval 09-Apr :13 GMT+02