Abstract
Background
To investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women.
Methods
In this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study.
Results
A total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG.
Conclusion
EV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population.
Clinical trials registry
ClinicalTrials.gov identifier: NCT01638910.
Supplementary materials
List of institutional review boards
China
The Second Hospital of Tianjin Medical University No 23, Ping Jiang Road, He Xi District, 300211 Tianjin
Peking Union Medical College Hospital Clinical Trial Office, No 41 Damucang Hutong, Xicheng District, 100730 Beijing
1st Affiliate Hosp., Dalian Med Univ. EC office No 222 Zhongshan Road, 116011 Dalian
The First Affiliated Hospital of Third Military Medical University, PLA 30, Gaotanyan Street, Shapingba District, 400038 Chongqing
Peking University People’s Hospital, No 11 South Avenue, Xizhimen, Xicheng District, 100044 Beijing
Renji Hospital, Shanghai Jiao Tong University, School of Medicine, No 1630 Dongfang Road, 200127 Shanghai
1st Affiliated Hospital, Guangzhou University, TCM No 16, Ji Chang Road, San Yuan Li, 510405 Guangzhou
Obstetrics & Gynecology Hospital of Fudan University, No 419 Fangxie Road, 200011 Shanghai
The Third Xiangya Hospital of Central South University Ethics Committee, No 138, Tongzipo Road, 410013 Changsha
Affiliated Ruijin Hospital Shanghai Jiao Tong University Med School Ethics Committee, No 197 Ruijin Er Road, 200025 Shanghai
People’s Hospital of Hebei Province Ethics Committee, No 348, West Peace Street, 050051 Shijiazhuang
The Third Affiliated Hospital of Third Military Medical University, No 10, Daping Changjiang Branch Road, Yuzhong District, 400042 Chongqing
The First Affiliated Hospital of Nanhua University, No 69, Chuanshan Road, 421001 Hengyang
The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical Hospital, No 306, Hualongqiao Road, Lucheng District, 325027 Wenzhou, Zhejiang Province. The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 325027 Wenzhou
International Peace Maternity and Child Health Hospital, No 910, Hengshan Road, 200030 Shanghai
West China Second University Hospital, No 17, 3rd Section of Renmin South Road, 610041 Chengdu
Family Planning Research Institute, Tongji Medical College, Huazhong University, Hangkong Road 13#, 430030 Wuhan
Qilu Hospital, Shandong University, No 107, Wenhua West Road, 250012 Jinan
Union Hospital of Tongji Medical College, Huazhong University, No 13, Hangkong Road, Wuhan 430030, Hubei
The Affiliated Zhongda Hospital of Southeast University, No 87, Dingjiaqiao Road, 210009 Nanjing
Hong Kong
Queen Mary Hospital HKU/HA HKW Institutional Review Board Room 901, Administration Block, Queen Mary Hospital, 102, Pokfulam Road, Hong Kong
India
Ruby Hall Clinic Poona Medical Research Foundation Medical Director, 40 Sasson Road, 411001 Pune
Bharti Research Institute of Diabetes and Endocrinology CLINICOM, “Sushruta”, #1/1, lst Temple Road, 15th Cross, Malleashwaram, 560003 Banglore
Sunshine Hospital Institutional Ethics Committee, Sunshine Hospitals, PG Road, Paradise, Secunderabad 500003
Thailand
King Chulalongkorn Memorial Hospital Institutional Review Board, Faculty of Medicine, Chulalongkorn University, 3rd Floor, Anuntamahidol Building, 1873 Rama IV Road, Pathumwan, 10330 Bangkok
Maharaj Nakorn Chiang Mai Hospital Research Ethics Committee, Faculty of Medicine, Chiang Mai University, 110 Intravaroros Road, Amphoe Muang, 50200 Chiang Mai
Siriraj Hospital, Mahidol Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkoknoi, 10700 Bangkok
Taiwan
Chang Gung Memorial Hospital at Linkou Institutional Review Board, Chang Gung Memorial Hospital (IRB/CGMH), No 123, Dinghu Road, Gueishan Township, 333 Taoyuan
Taichung Veterans General Hospital, The Institutional Review Board 160, Section 3, Tai-Chung-Kang Road, 40705 Tai-Chung
Kaohsiung Medical University Chung-Ho Memorial Hospital Clinical Pharmacy, No 100, Tzyou 1st Road, Kaohsiung
National Taiwan University Hospital, No 7, Chung-Shan South Road, 10016 Taipei
Taipei Veterans General Hospital, No 201, Section 2, Shih Pai Road, 11217 Taipei
Taipei Municipal Wanfang Hospital, Taipei Medical University–Joint Institutional Review Board, No 1, Aly. 59, Ln. 220, Wuxing Street, Xinyi District, 110 Taipei
Table S1 Study drug-related TEAEs leading to treatment discontinuation in the safety analysis set (n=954)
Acknowledgments
The authors would like to thank Nishad Parkar of inScience Communications, Springer Healthcare, for writing the outline and the first draft of this manuscript, and Sarah Greig of inScience Communications, Springer Healthcare, for post-submission revisions. This medical writing assistance was funded by Bayer Healthcare Pharmaceuticals. The authors would also like to thank all the study site investigators and patients who participated in the study. This study was funded by Bayer Healthcare Pharmaceuticals.
Disclosure
ZZ is an employee of Bayer Healthcare. SP is an employee of Bayer Pharmaceuticals. The authors report no other conflicts of interest in this work.