Efficacy, safety, and tolerability of a monophasic oral contraceptive containing nomegestrol acetate and 17β-estradiol: a randomized controlled trial.

Objective: To estimate the efficacy, cycle control, tolerability, and safety of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-estradiol (E2) in comparison with drospirenone and ethinyl E2.

Methods: In a randomized, open-label, comparative multicenter trial, healthy women (n=2,281; age 18-50 years) at risk for pregnancy and in need of contraception were allocated in a 3:1 ratio to receive nomegestrol acetate (2.5 mg) and 17β-E2 (1.5 mg) in a 24-4-day regimen (investigational drug) or drospirenone (3.0 mg) and ethinyl E2 (30 micrograms) in a 21-7-day regimen (comparator) for 13 consecutive, 28-day cycles. The primary end point was the Pearl Index.

Results: The Pearl Indices for 18- to 35-year-old women in the investigational (n=1,375) and comparator (n=463) groups were 1.27 (95% confidence interval [CI] 0.66-2.22) and 1.89 (95% CI 0.69-4.11), respectively. Respective 1-year cumulative pregnancy rates were 1.22 (95% CI 0.69-2.16) and 1.82 (95% CI 0.81-4.05). By the end of the trial, shorter, lighter scheduled bleeding or an absence of scheduled bleeding occurred with greater frequency (32.9%) in the investigational group, whereas unscheduled bleeding or spotting episodes were low (16.2% and 15.0% in the investigational and comparator groups, respectively). Acne prevalence decreased from approximately 33% at baseline to 22% and 14% at cycle 13 in the respective groups. In the investigational group, the most frequently reported adverse events were acne (16.4%), weight gain (9.5%), and irregular withdrawal bleeding (9.1%).

Conclusion: Nomegestrol acetate and 17β-E2 were well tolerated and provided excellent contraceptive efficacy and acceptable cycle control.

Clinical Trial Registration: Clinicaltrials.gov, www.clinicaltrials.gov, NCT00413062.

Level Of Evidence: I.