Efficacy and safety of a novel oral contraceptive based on oestradiol (oestradiol valerate/dienogest): A Phase III trial

Objective: A novel oral contraceptive (OC) that contains oestradiol valerate (E2V; 1 mg of E2V is equivalent to 0.76 mg of 17beta-oestradiol) and dienogest (DNG) has been developed. The efficacy and safety of this formulation was assessed in the current study. Study design: This was a multicentre, open-label, non-comparative, 20-cycle study conducted in Germany, Austria and Spain in healthy women aged 18-50 years. E2V/DNG was administered using an oestrogen step-down and a progestin step-up approach over 26 days (E2V 3 mg on days I and 2. E2V 2 mg/DNG 2 mg on days 3-7, E2V 2 mg/DNG 3 mg on days 8-24, E2V I mg on days 25 and 26 and placebo on days 27 and 28). The primary outcome measure was the number of pregnancies during treatment in the whole study population and in the subgroup of women aged 18-35 years. Contraceptive efficacy was estimated by calculating the Pearl Index (number of pregnancies per 100 women - years of exposure). At a final examination, treatment satisfaction was assessed. Results: In total, 1377 women received Study treatment. During the Study, thirteen pregnancies occurred (unadjusted Pearl Index: 0.73). Six of these were due to method failure (adjusted Pearl Index: 0.34). In the subgroup of 998 women aged 18-35 years, 12 pregnancies occurred (unadjusted Pearl Index: 0.94), five of which were due to method failure (adjusted Pearl Index: 0.40). The majority of women (79.5%) were satisfied or very satisfied with treatment. Treatment-related adverse events (considered at least possibly treatment-related) occurred in 19.8% of women. Overall, during 20 cycles of treatment, only 10.2% of women prematurely discontinued treatment due to an adverse event. Conclusions: A novel OC based on oestradiol provides highly effective and reliable contraception. This is achieved through the combination of oestradiol valerate (E2V) and dienogest (DNG) administered using an oestrogen step-down and a progestin step-up approach over 26 days of active treatment followed by 2 days of placebo. The preparation is well tolerated and is associated with a high degree of user satisfaction and a low discontinuation rate. (C) 2009 Elsevier Ireland Ltd. All rights reserved.