Clinical Study Synopsis

Transcription

1 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. The results from a single study may not reflect the overall results for a drug. The following information is the property of Bayer HealthCare AG. Reproduction of all or part of this report is strictly prohibited without prior written permission from Bayer HealthCare AG. Commercial use of the information is only possible with the written permission of the proprietor and is subject to a license fee. Please note that the General Conditions of Use and the Privacy Statement of bayerhealthcare.com apply to the contents of this file.

2 Clinical Trial Results Synopsis Study Design Description Study Sponsor: Bayer Healthcare AG Study Number: (BF0814KR) Study Phase: IV (Observational) NCT Official Study Title: Betaferon regulatory Post Marketing Surveillance Therapeutic Area: Neurology Test Product Name of Test Product: Name of Active Ingredient: Dose and Mode of Administration: Interferon beta-1b (Betaseron, BAY ) Interferon beta-1b(bay ) 250 μg as reference dose via subcutaneous injection Reference Therapy/Placebo Reference Therapy: NA Dose and Mode of Administration: NA Duration of Treatment: Treatment duration was decided by attending physician. Studied period: Date of first subjects first visit: 08 APR 2008 Date of last subjects last visit: 30 JUL 2012 Study Center(s): This study was conducted at 39 centers in Korea Methodology: To ascertain the existence of unknown adverse events after the administration of Betaferon, the investigators collected all abnormal symptoms regardless of relevance to Betaferon. And the investigators collected concomitant medications and factors which can affect safety and efficacy. Indication/ Main Inclusion Criteria: Inclusion Criteria : 1) Patients with diagnosis of Multiple Sclerosis (MS) or Clinically Isolated Syndrome (CIS) and decision taken by the physician to prescribe Betaferon 2) Patients who have not participated in Betaferon regulatory Post Marketing Surveillance before. Page 1 of 5

3 Study Objectives: To identify problems/questions about following items in the clinical practice using Betaferon: Primary: Safety variables will be summarized using descriptive statistics based on adverse events(ae). Secondary: 1) The efficacy data regarding prevention of relapse due to MS will be estimated based on the number of relapse. 2) Progression or aggravation to Multiple sclerosis (MS) will be identified based on the change of Expanded Disability Status Scale(EDSS) and the Magnetic Resonance Imaging (MRI) outcome. Evaluation Criteria: Efficacy: 1) The efficacy data regarding prevention of relapse due to MS will be estimated based on the number of relapse. 2) Progression or aggravation to Multiple sclerosis (MS) will be identified based on the change of Expanded Disability Status Scale(EDSS) and the Magnetic Resonance Imaging (MRI) outcome Safety: Safety variables will be summarized using descriptive statistics based on adverse events. Page 2 of 5

4 Statistical Methods: Efficacy: Descriptive statistics (mean, standard deviation, minimum and maximum) were presented for EDSS(Expanded Disability Status Scale) scores and number of lesion in T2(MRI) changes between at the start of treatment and the end of treatment with paired t-test (or Wilcoxon signed-rank test). The number and percentage of patients who were assessed as effective/non-effective to betaferon treatment were summarized as frequency distribution by demographic/medical characteristics, concomitant therapy, extent of exposure to betaferon and special population group. Univariate (Chi-square test or Fisher s exact test) and multivariate (logistic regression) analyses were performed. Number of Subjects: Safety: The adverse events were coded using WHO Adverse Reactions Terminology (WHOART), Version 092 and summarized by system organ class and preferred term. The categorical variables were summarized with numbers and percentages, and the analysis for the variables was performed using Chi-square test or Fisher s exact test. The number and percentage of patients with adverse event were summarized as frequency distribution by demographic/medical characteristics, concomitant therapy, extent of exposure to betaferon and special population group. Univariate (Chi-square test or Fisher s exact test) and multivariate (logistic regression) analyses were performed. Multiple logistic regression was used to assess the association between adverse events and background factors. Presenting odds ratio (OR) and 95% Confidence interval (CI), multivariate analysis was performed by classifying demographic characteristics as independent variables and incidence of adverse event as dependent variables. 369 patients were enrolled and safety evaluation was performed for 355 patients and efficacy analysis were performed for 345 patients. Page 3 of 5

5 Results Summary Subject Disposition and Baseline Study Results This re-examination aims to check occurrence and rate of AE/SAE and to find the factors affecting safety and efficacy for patients who have MS or CIS. 369 patients were enrolled in 39centers. Except double recruited and contra-indicated patients, 355 patients were evaluated for safety. 345 patients (except 10 patients who were administered Betaferon below 3 months) were evaluated for efficacy. According to basic demographics of patients, average age was ± years. As a result of investigation in diagnosis (using the Betaferon reasons), patients with multiple sclerosis (MS) were 322 patients (90.70%), Clinically Isolated Syndrome (CIS) were 33 patients (9.30%). Average prevalence period was ± month, prevalence period was less than one month for the 196 people (56.00%), 154 people (44%) showed prevalence of period in excess of one-month. Patients with concomitant medication were investigated for 239 (67.32%), and the number of the administered drugs were 1,008. As a result of the investigation, 166 patients (69.46%) were administered nervous system-family drug which was most commonly used and the number of the administration was counted 348. In detail information was that 98 patients (41.00%) were administered antiepileptics that was counted 147, 50 patients (20.92%) were administered respectively psychoanaleptics (71) and analgesics (69). 26 patients (10.88%) were administered psycholeptics that was counted 41. Other nervous system drugs were treated to 14 patients (5.86%) and the used number were 14. Results Summary Efficacy Efficacy analysis was carried out of 345 people, except for 10 patients among the 355 safety population. Evaluation of the efficacy were performed with EDSS (Expanded Disability Status Scale) score changes, MRI bottle-check (Number of lesions in T2). Efficacy was assessed by usability and ' very useful ', 'useful ' and 'not useful' three grades were classified as. The overall efficacy assessment was investigated from the doctor whether the effective for ' valid ' or for ' null and void ' after Betaferon administration. Overall effectiveness was assessed as 'very useful' in 160 patients (46.38%), ' useful ' in 176 patients (51.01%) and ' not useful ' in 9 patients (2.61%). To evaluate factors affecting effectiveness, logistic regression analysis was used with factors such as age, hospitalization/outpatient classification, prevalence, disease, foot disease, since the force, whether valid independent variable antiretroviral, two dependent by logistic regression analysis. As a result, each of the factors did not impact analysis. Specifically, the efficacy was valuable regardless of high and low of age (OR: 1.00, 95% CI: 0.95 ~ 1.06). Patients who were outpatients (OR: 2.32, 95% CI: 0.46 ~ 11.56), had prevalence over one month (OR: 3.00, 95% CI: ), had concomitant disease (OR: 1.12, 95% CI: 0.21 ~ 6.04), had no medical history(or: % CI: 0.13 ~ 3.87) and who were greater than 1, 000 days for administration period (OR: 2.09, 95% CI: ) were more efficient than others. But there were no factors statistically significant. Page 4 of 5

6 Results Summary Safety During the re-examination period, 96 adverse events (AEs) were reported by 59 patients (16.62%) out of 355 patients included in safety evaluation and 35 adverse drug reactions (ADRs) were reported by 23 patients (6.48%). 34 unexpected AE were reported by 25 patients (7.04%), 16 serious adverse events (SAE) were reported by 9 patients (2.54%). 3 serious adverse drug reactions were reported by 2 patients (0.56%) 34 unexpected AEs occurred in 25 patients (7.04%) during this re-examination period which were nervous system disease, musculoskelata disorders, urologic disorders, visual impairment disorders, other gastrointestinal disorders, hearing impairment as quadratic terms. Reported as a serious adverse event were the nervous system disease 7 cases/6 patients (1.69 %), visually impaired disease 4 cases/3 patients (0.85%), musculoskeletal diseases 2 cases/2 patients (0.56%), application site disease 2 cases/1 patient (0.28%) and mental disorders disease 1 case/1 patient (0.28%). To evaluate factors affecting AE occurrence, logistic regression analysis was used with factors such as age, hospitalization/outpatient classification, diagnosis, prevalence, medical history, concomitant medications, dose of allergen and treatment period. As a result of multivariate analysis, presence or absence of concomitant medication was a statistically and significantly related to the occurrence of AEs. Specifically, patients with the concomitant medication had higher possibility of AE occurrence than patients without concomitant medication (OR: 8.58, 95% CI: 2.54 to 29.00, p = ). Conclusion(s) In conclusion, the incidence of AEs was 16.62% in patients who used Betaferon during this surveillance period. 16 SAEs and 34 unexpected AEs were reported. The univariate and multivariate analyses by factor affecting occurrence of AEs showed that concomitant medications were statistically and significantly related to the occurrence of AEs. The overall effectiveness of the Betaferon was assessed as 'very useful' 46.38%, 'useful' 51.01% and not 'useful' 2.61%. In the future clinical practice, information on adverse events will be continuously collected including voluntary reporting, and the results of this report and future collected information will be used according to scientific and ethical consideration. Publication(s): None Date Created or Date Last Updated: 11 Jul 2013 Page 5 of 5

7 Appendix to Clinical Study Synopsis Product Identification Information Product Type US Brand/Trade Name(s) Brand/Trade Name(s) ex-us Generic Name Main Product Company Code Biological product Betaseron Betaseron, Betaferon Interferon beta 1b BAY Other Company Code(s) ZK Chemical Description Recombinant protein Other Product Aliases Date of last Update/Change: 12 Sep 2012