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. Reproduction of all or part of this report is strictly prohibited without prior written permission from Bayer HealthCare. 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 Study Sponsor: Bayer Healthcare Clinical Trial Results Synopsis Study Design Description Study Number: (YA0910KR, YAZ rpms) Study Phase: IV (Observational) Official Study Title: NCT Regulatory Post marketing Surveillance to assess efficacy and safety of using YAZ in the Korean population in clinical practice Therapeutic Area: Women s Healthcare Test Product Name of Test Product: Name of Active Ingredient: Dose and Mode of Administration: Reference Therapy/Placebo Reference Therapy: Not Applicable Dose and Mode of Administration: Duration of Treatment: EE20/DRSP (YAZ, BAY ) Drospirenone (DRSP) and ethinyl estradiol (EE) combination (BAY ) The treatment with Daily oral administration of one tablet YAZ for 28 days (YAZ 24/4 regimen, 3.0 mg DRSP + 20mcg EE for 24days / Placebo for 4days) should comply with recommendation written in the local product information. The decision on the duration and closure of treatment is solely at the discretion of the attending physician. Not Applicable The decision on the duration and closure of treatment is solely at the discretion of the attending physician. Early Termination: Not Applicable Studied period: Date of first subjects first visit: Date of last subjects last visit: 14-Jul Nov-2011 Study Center(s): This study was conducted in 68 sites in Korea Page 1 of 8

3 Methodology: This study is local prospective, company sponsored, non interventional study of patient who have been treated with YAZ for contraception, Premenstrual dysphoric disorder (PMDD), acne. YAZ 24/4 regimen (3.0 mg DRSP + 20mcg EE for 24days / Placebo for 4days) will be studied. There will be no control group. A total of 600 generally healthy women 18 to 50 years of age desiring contraception with or without PMDD or acne will be recruited. The duration of patient follow up will be the end of 6th cycle of treatment. The decision on the duration and closure of treatment is solely at the discretion of the attending physician. Contraceptive efficacy will be calculated as the efficacy variable in this study. Contraceptive efficacy will be evaluated by pregnancy test (positive/negative) and compliance will be evaluated by comparison of no. of taken pill and prescribed pills. The release of PMDD or acne also will be calculated as the efficacy variable if indication of YAZ prescription would be PMDD or acne. Adverse Events (AE) / Adverse Drug Reactions (ADR) will be evaluated as safety variables. Symptoms, Serious Adverse Event (SAE) or not, reason to be considered as SAE, Severity, Time of onset (yyyy/mm/dd), Time of vanishing symptom, outcome, treatment (action taken), and relationship with YAZ will be recorded. Adverse events will be recorded by physician and physician have to ask whether she experienced any AE on every visit. General safety will be assured prior to entry and monitored during the study. Page 2 of 8

4 Indication/ Main Inclusion Criteria: Inclusion Criteria: Healthy female subjects o requesting contraception o suggesting PMDD by Physician who are also requesting contraception o with acne who are also requesting contraception Age: years Women who is prescribed YAZ first, during study period Exclusion Criteria: Women who are contraindicated based on the label of YAZ o Presence or a history of venous or arterial thrombotic/ thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident o Presence or history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris) o History of migraine with focal neurological symptoms o Diabetes mellitus with vascular involvement o The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication o Pancreatitis or a history thereof if associated with severe hypertriglyceridemia o Presence or history of severe hepatic disease as long as liver function values have not returned to normal o Severe renal insufficiency or acute renal failure o Presence or history of liver tumours (benign or malignant) o Known or suspected sex-steroid influenced malignancies (e.g. of the genital organs or the breasts) o Undiagnosed vaginal bleeding o Known or suspected pregnancy o Hypersensitivity to the active substances or to any of the excipients Page 3 of 8

5 Study Objectives: Evaluation Criteria: Overall: The objective of this YAZ regulatory post marketing surveillance study are to assess efficacy and safety of using YAZ in the Korean population in clinical practice. To obtain safety data, these data below should be included. 1) SAE, ADR 2) Unexpected ADR 3) Known / proven ADR 4) AE 5) AE regarding overdose, misuse and drug interaction 6) other safety parameters And to obtain data of drug utilization on each indication, 1) indication just for contraception, 2) indication for PMDD with needs of contraception, 3) indication for treatment of acne with needs of contraception. Primary: Safety and Efficacy of YAZ in the Korean population in clinical practice Secondary: to obtain data of drug utilization(%) on each indication. 1) indication just for contraception, 2) indication for PMDD with needs of contraception, 3) indication for treatment of acne with needs of contraception. Efficacy: 1) Contraceptive efficacy - Compliance (%): Administrated tab No. / Prescribed tab No. X Pregnancy Test: Positive / Negative 2) Treatment efficacy on PMDD: Release of PMDD symptom - check box (much better/better/no change/worsen) 3) Treatment efficacy on acne: Release of Acne - check box (much better/better/no change/worsen) Safety: Presence of Adverse Events / Adverse Drug Reactions or not - Symptoms, Serious Adverse Event or not, reason to be considered as SAE, Severity, Time of onset (yyyy/mm/dd), Time of vanishing symptom, outcome, treatment (action taken), and relationship with YAZ will be recorded. - Severity evaluation: Severity of AE Symptoms will be assessed according to following criteria, and Serious Adverse Events / Adverse Drug Reactions should be assessed according to Management of Serious Adverse Events / Adverse Drug Reactions. Page 4 of 8

6 Statistical Methods: Efficacy (Primary) - if applicable: The data from participant who would have analyzed for safety profile and whose efficacy data is recorded in compliance with planned protocol will be analyzed for efficacy profile. Questions to overall evaluation of the YAZ therapy and other efficacy related data will be summarized and described by presenting frequency distributions and/or basic summary statistics. 1) Contraceptive efficacy - Compliance (%): Administrated tab No. / Prescribed tab No. X Pregnancy Test: Positive / Negative 2) Treatment efficacy on PMDD - check box (much better/better/no change/worsen) for each visit - Benefit of YAZ for final visit will be assessed as 1= Very Useful, 2= Useful, 3= Undesirable 3) Treatment efficacy on acne - check box (much better/better/no change/worsen) for each visit - Benefit of YAZ for final visit will be assessed as 1= Very Useful, 2= Useful, 3= Undesirable Safety: The data from any participant who have taken YAZ more than just one time will be analyzed for safety profile. Any abnormality during physical and Gynecologic exam will be recorded by physician. Adverse events will be summarized using the Medical Dictionary for Regulatory Activities (MedDRA) coding system version Special attention will be paid to serious adverse events. Number of Subjects: More than 600 women in total were planned. During study period, 770 subjects were enrolled. Of those, 6 subjects were excluded due to violation of inclusion criteria (age violation 5 subjects, indication of YAZ tablet missing 1 subject), the remaining 764 subjects were evaluated for safety. And 2 subjects were excluded due to 'pregnancy test result missing', a total of 762 subjects were evaluated for efficacy. Substantial Protocol Changes: The study was conducted according to final Study Protocol V1.3 from date 26May2009, and included no substantial amendments. Page 5 of 8

7 Results Summary Subject Disposition and Baseline Study Results During study period, a total 770 subjects were enrolled from 68 sites. 764 subjects were evaluated for safety and 762 subjects were evaluated for efficacy. Among the total of 764 subjects, all subjects were women. Mean age was 28.65±6.56 years old (ranging from 18 to 50 years old). The most dominant group was 20~29 years old group with 59.29%(453/764 subjects). There was no subject classified as '65 years and over' and 'below 12 years'. 57 subjects (7.46%) had past history and 87 subjects (11.39%) had concurrent disease. Concurrent disease was shown as 'Urinary and productive system disease' 52.87% (46/87 subjects), 'Neoplasm' 14.94% (13/87 subjects) and so on. The subjects who had ever experienced pregnancy were 300 subjects. Mean gravidity was 0.79±1.12 times (ranging from 0 to 9 times). The subjects who had ever experienced birth were 194 patients. Mean parity was 0.44±0.80 times (ranging from 0 to 4 times). Mean amenorrhea period (start date of study drug - last menstruation date) was 21.05±39.52 days. The subjects who had ever experienced contraception were 298 subjects. The indication of YAZ tablet were 'Contraception and PMDD treatment' 48.17%(368/764 subejcts), Only 'Contraception' 42.28% (323/764 subjects), 'Contraception and acne treatement' 15.05%(115/764 subjects) in order. During study period, 78 subjects had taken concomitant medications. The concomitant medicaiton was counted by KIMS (Korean Index of Medical Specialities) system with overlap count and classified by organ system. It was shown as 'Anti-infectives (systemic)' 65.38%(51/78 subjects), 'Central Nervous System' 26.92%(21/78 subjects), 'Gastrointestinal & Hepatobiliary System' 25.64%(20/78 subjects) and so on in order. The subjects who had used YAZ tablet over 180 days were classified as 'Long term user', 329 subjects were long term user. Page 6 of 8

8 Results Summary Efficacy As a result of efficacy evaluation, among all the subjects of safety evaluation, 762 subjects was evaluated for efficacy. Compliance of YAZ tablet for the patient for 'Contraception' mainly was shown as '90 ~ 99%' 53.25% (172/323 subjects), '100%' 33.75% (109/323 subjects), '80~89%' 5.26% (17/323 subjects) and so on in order. Compliance of YAZ tablet for 'Contraception and PMDD treatment' was shown as '90~99%' 48.90% (178/364 subjects), '100%' 25.82% (94/364 subjects), '80~89%' 13.46% (49/364 subjects) and so on in order. Compliance of YAZ tablet for 'Contraception and acne treatment' was shown as '90~99%' 55.65% (64/115 subjects), '100%' 20.87% (24/115 subjects), '80~89%' 11.30% (13/115 subjcets) and so on in order. During study period, there was no reported cases with pregnancy. Efficacy for PMDD treatment was conducted into 4 steps according to general efficacy evaluated by the physician in charge of PMS at the end of the PMS. As a result of efficacy evaluation for PMDD, it was shown as 'Better' 59.84% (219/366 subjects), 'Much better' 32.51% (119/366 subjects), 'No change' 7.10% (26/366 subjects), 'Worsen' 0.55% (2/366 subjects) in order. Efficacy for Acne treatment was conducted into 4 steps according to general efficacy evaluated by the physician in charge of Post-Marketing Surveillance (PMS) at the end of the PMS. As a result of efficacy evaluation for Acne, it was shown as 'Better' 56.03%(65/116 subjects), 'Much better' 26.72% (31/116 subjects), 'No change' 14.66% (17/116 subjects), 'Worsen' 2.59% (3/116 subjects) in order. Results Summary Safety During the PMS period, total 82 events of AEs were reported in 62 subjects (8.12%, 62/764 subjects) of all the subjects. Details of the reported AEs were as follows: Vaginal haemorrhage 1.70% (13/764 subjects), Vaginitis 1.18% (9/764 subjects), Uterine haemorrhage, Acne as each 0.79% (6/764 subjects), and so on. Out of them, 53 ADRs, in which causality with YAZ tablet cannot be excluded, were reported in 45 subjects (5.89%). Details of the reported ADRs were as follows: 'Vaginal haemorrhage' 1.57%(12/764 subjects), 'Uterine haemorrhage', 'Acne as each 0.79% (6/764 subjects), 'Breast pain', 'Headache', 'Haemorrhage nos' as each 0.39% (3/764 subjects), and so on. Among AEs reported during the PMS period, the total number of unexpected AEs irrespective of their relation to the study medication was 36 cases in 32 subjects (4.19%, 32/764 subjects). Details of the reported unexpected AEs were as follows: Vaginal haemorrhage 1.70% (13/764 subjects), Dysmenorrhoea', 'Haemorrhage nos as each 0.39% (3/764 subjects), Herpes genital', 'Rash' as each 0.26% (2/764 subjects), and so on. Among unexpected AEs, 26 ADRs, in which causality with YAZ tablet cannot be excluded, were reported in 24 subjects (3.14%, 24/764 subjects). Details of the unexpected ADRs were as follows: Vaginal haemorrhage 1.57% (12/764 subjects), Haemorrhage nos 0.39% (3/764 subjects), Dysmenorrhoea', 'Rash as each 0.26% (2/764 subjects). During the whole PMS period, there was no reported SAE. In the analysis of factors affecting safety and incidence of AEs by factor, experience of contraception(p<0.0001), concomittant medications(p<0.0001) were statistically significant. Page 7 of 8

9 Conclusion(s) In conclusion, overall incidence rate of AE was 8.12%, out of those, 36 unexpected adverse events were reported from 32 subjects (4.19%). Serious adverse events were not reported. The factors like experience of contraception and concomitant medications were statistically related to safety. As a result of medication compliance and pregnancy test to evaluate efficacy of YAZ tablet. The most dominant group in compliance was '90%~99%' in all indication, and all patients included in efficacy evaluation was negative in pregnancy test. As a result of general efficacy, in physicians and subjects, the most dominant group was 'Better'. As above, PMS during the period of review of YAZ tablet showed that no specific trend was present, compared to the reported onset of AEs, and no specificity likely to influence safety and efficacy was not found. In the future, YAZ tablet is to be continuously observed through spontaneous report or report of AEs from studies. Publication(s): None at the time of report creation Date Created or Date Last Updated: 10-Jul-2014 Date Created or Date Last Updated: 22-Jan-2014 Page 8 of 8

10 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 Other Company Code(s) Drug YAZ YAZ, Dschess, Dzhes, Dzhess, Eloine, Ethinylestradiol/Drospirenon 24+4, Ethinylestradiol/Drospirenone, Leah, Linatera, Rimendia, Yasmin 24/4, Yasminiq, Yaz 24+4, YAZZ 24+4, Yvette Drospirenone; Ethinylestradiol BAY SH T 186 DF Chemical Description Drospirenone: 6ß,7ß;15ß,16ß-Dimethylene-3-oxo-17alpha-pregn-4-ene- 21,17-carbolactone Ethinylestradiol: 17 alpha-ethynyl-1,3,5(10)-estratriene-3,17 ß-diol Other Product Aliases Yasmin 20 Date of last Update/Change: 09 Apr 2013