Kristina Gemzell-Danielsson1, Dan Apter2, Sylvia Dermout3, Thomas Faustmann4, Kimberly Rosen5, Thomas Schmelter4, Martin Merz6, Anita Nelson7. 1. Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 2. VL-Medi Clinical Research Center, Helsinki, Finland. 3. Gynaecological Centre Dermout & Albicher, Alkmaar, The Netherlands. 4. Bayer Pharma AG, Berlin, Germany. 5. Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA. 6. Bayer Pharma AG, Berlin, Germany. Electronic address: martin.merz@bayer.com. 7. Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, CA, USA.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use. STUDY DESIGN: In this Phase III study, 2885 nulliparous and parous women aged 18-35 years were randomized to LNG-IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction. RESULTS:From August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months. CONCLUSION: In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG-IUS 12 offers women a low-dose contraceptive option for up to 5 years.
RCT Entities:
OBJECTIVE: To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use. STUDY DESIGN: In this Phase III study, 2885 nulliparous and parous women aged 18-35 years were randomized to LNG-IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction. RESULTS: From August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months. CONCLUSION: In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG-IUS 12 offers women a low-dose contraceptive option for up to 5 years.