Clinical Study Synopsis
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Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their treatment. Healthcare Professionals should always refer to the specific labelling information approved for the patient's country or region. Data in this document or on the related website should not be considered as prescribing advice. The study listed may include approved and non-approved formulations or treatment regimens. Data may differ from published or presented data and are a reflection of the limited information provided here. The results from a single trial need to be considered in the context of the totality of the available clinical research results for a drug. 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Clinical Trial Results Synopsis Study no. 16599 Page: 1 of 13 Date of study report: 18 DEC 2013 Study title: A 28-day, double-blind, randomized, reference-controlled open Psoriasis Plaque Test for within subject comparison of efficacy and safety of Mapracorat 0.1% ointment and 4 reference products in symptomatic volunteers with stable plaque-type psoriasis Sponsor’s study 16599 number: NCT number: NCT03399526 EudraCT number: 2012-004171-39 Sponsor: Bayer HealthCare Clinical phase: Phase I Study objectives: Evaluation of efficacy and safety of mapracorat 0.1% ointment and 4 comparator ointments in male and female subjects 18-65 years with stable plaque-type psoriasis treated once daily 6 days a week for a maximum of 4 weeks. Primary objective was to compare the efficacy of all test compounds by measurement of psoriatic infiltrate thickness (PIT) with 20 MHz B mode ultrasound. Secondary objectives were: To assess safety of all test compounds by measurement of the atrophogenic potential on non-lesional skin with 20 MHz B mode ultrasound. To assess the efficacy of all test compounds by measurement of intensity of erythema measured by chromametry. To assess the efficacy of all test compounds by visual assessment of the skin in the test fields using a 5-point score. To assess the safety of all test compounds by visual assessments of formation of telangiectasia using a 5-point score. To assess the safety of all test compounds by visual assessment of atrophy using a 5-point score. To assess the safety of all test compounds by visual assessment of local tolerability using a 5-point score. To visualize the therapeutic index given by PIT versus non-lesional skin thickness. Test drug: Mapracorat (ZK 245186, BAY 86-5319) Name of active Mapracorat ingredient(s): Clinical Trial Results Synopsis Study no. 16599 Page: 2 of 13 Dose: 10 µL on 6 days a week for 4 weeks (24 applications), open topical application on a psoriasis plaque 200 µL on 6 days a week for 4 weeks (24 applications), topical application under occlusion on uninvolved skin Route of Topical, non-occlusive, and occlusive application administration: Duration of treatment: Once daily 6 days a week for a maximum of 4 weeks Reference drug: Prednicarbate 0.25% ointment Clobetasol 0.05% ointment Calcipotriene 0.005% ointment Calcipotriene 0.005%/Betamethasone dipropionate 0.05% ointment Dose 10 µL on 6 days a week for 4 weeks (24 applications), open topical application on a psoriasis plaque 200 µL on 6 days a week for 4 weeks (24 applications), topical application under occlusion on uninvolved skin Route of administration Topical, non-occlusive, and occlusive application Duration of treatment Once daily 6 days a week for a maximum of 4 weeks Indication: Psoriasis Diagnosis and main Male or female Caucasian subjects 18-65 years of age with stable criteria for inclusion: plaque-type psoriasis, plaques of adequate size to allow for evaluation of 5 test fields, on comparable body area; thickness of the echo-lucent band under the entry echo as assessed by ultrasound of at least 200 μm Study design: The study was conducted in a double-blind, reference-controlled, randomized, single-center, within subject comparison design Methodology: The study comprised a screening, treatment, and follow-up period. During screening, the medical history was recorded and the severity of symptoms of the psoriatic target plaques was assessed in order to record potential changes to the baseline examination. During the 28-day treatment phase, the study preparations were applied on 6 days a week openly to the predetermined plaques, and in an occlusive fashion on non-lesional skin on the volar forearm. Assessments were made two times per week. The study ended on Day 60 with the last assessments after ultrasound measurements of skin thickness. Efficacy (estimated by Psoriasis Plaque Test): Psoriasis target plaque(s) were repeatedly treated on defined test fields. 10 µL of each ointment were applied on 6 days a week for up to 4 weeks onto the corresponding test fields (3 cm2) of the affected skin plaques (15 cm2 were treated in total [diameter 2 cm, distance to next test field at least 2 cm]). Evaluations were done by within subject comparison of treated areas using both objective (psoriatic Clinical Trial Results Synopsis Study no. 16599 Page: 3 of 13 infiltrate measured by high-frequency ultrasound, erythema measured by chromametry) and subjective measurements (visual assessment). Ultrasound for PIT assessment and erythema measurements were performed prior to drug administration from Day 1 and up to Day 29 (end of study medication [EOSM] visit). Visual assessment of efficacy was performed prior to drug application on Day 4 and up to Day 29 (EOSM visit). Safety: Non-lesional skin areas of 2.5 cm2 were repeatedly treated on defined test fields (12.5 cm2 were treated in total [diameter 1.8 cm, distance to next test field at least 1.5 cm]) occluded with Finn chambers. 200 µL of each ointment were applied on 6 days a week for up to 4 weeks onto the corresponding test fields. Finn chambers were fixed with hypoallergenic tape and left in place for 24 or 48 h, respectively. Evaluation was done by within subject comparison of treated areas using skin thickness measured by high-frequency ultrasound and visual assessment. Adverse events (AEs) were recorded. Laboratory tests at screening were performed. Clinical assessments of atrophy, local tolerability, and telangiectasia were performed prior to drug application from Day 1 and up to Day 29 (EOSM visit). Ultrasound measurement of skin thickness (occluded test fields) was performed prior to drug application from Day 1 and up to Day 60 (end of study [EOS] visit). The study period duration ranged between 64 and 84 days. Safety and tolerability of mapracorat were monitored throughout the study. Study center(s): The study was conducted at a single center in Germany. Publication(s) based on None at the time of report creation the study (references): Study period: Study Start Date: 11 FEB 2013 Study Completion Date: 31 MAY 2013 Early termination: Not applicable Number of subjects: Planned: 24 subjects Analyzed: 24 subjects Criteria for evaluation Efficacy: Efficacy measurements were made on the test fields on psoriatic plaques. Primary variable: Baseline-corrected area under the curve (AUC) of the PIT measured by 20 MHz B mode ultrasound Secondary variables: PIT measured by 20 MHz B mode ultrasound Measurement of erythema using chromametry (mean of triplicate Clinical Trial Results Synopsis Study no. 16599 Page: 4 of 13 measurement) Clinical efficacy assessment of the skin in the test fields using a 5-point score Safety: The incidences of treatment-emergent AEs (TEAEs) including cutaneous AEs were considered safety variables. Vital signs (including blood pressure [BP] and heart rate [HR]), screening laboratory examination (hematology, serum biochemistry, virology, urinalysis), pregnancy testing, extent of exposure Clinical pharmacology: Pharmacodynamics: Pharmacodynamic (PD) assessments were made on occluded test fields on non-lesional skin areas on the forearm: Skin thickness measurement of occluded test field on non-lesional skin (mean of triplicate measurement) Clinical assessment of atrophy using a 5-point score Clinical assessment of telangiectasia using a 5-point score Clinical assessment of local tolerability using a 5-point score Others: Visualization of the therapeutic index Statistical methods: The AEs were coded using the medical dictionary for regulatory activities (MedDRA) Version 15.1. The primary variable “baseline corrected-area under the curve (AUC) of the PIT,” measured with a 20 MHz B mode ultrasound was used to compare the efficacy of all test compounds. The primary objective was achieved using analysis of variance (ANOVA) techniques on the primary variable. The analysis of secondary variables (achievement of secondary objectives) followed after the analysis of the primary variables. The AUC per treatment field was calculated for PIT measured by 20 MHz ultrasound. For AUC calculation, the baseline value of each subject and test field was subtracted from the actual measurement in order to account for differences at baseline between test fields and subjects. The resulting variable was referred to as change from baseline in PIT (cPIT) determined as PITtn-PITt1. The AUC was subsequently calculated using the trapezoidal rule. Thus, for the variable cPIT, the AUC from time interval first visit (t1=1) to end of study medication visit (t9=29) was calculated using the following equation: The AUC per treatment was presented in µm x day using descriptive Clinical Trial Results Synopsis Study no.