The aim of this open, noncontrolled phase III study was the assessment of the contraceptive efficacy and the evaluation of the safety of long-term use of Belara (30 micrograms ethinyl estradiol plus 2 mg chlormadinone acetate). Furthermore, cycle stability during administration of Belara and the influence of Belara on acne and seborrhea as clinical signs of androgenization were observed. Belara was taken by 1655 women for a total of 22,337 cycles. For the theoretical Pearl index, a value of 0.269 (95% CI [0.109, 0.600]) was calculated. In 1655 of 22,337 cycles (7.4%), no withdrawal bleeding was documented, whereas in 2565 of 22,308 cycles (11.5%), spottings and, in 786 of 22,308 cycles (3.5%), breakthrough bleeding occurred. After the intake of Belara for 12 cycles, acne on the face/neck improved in 64.1% of the women (209 of 326). In 53.4% of the women (175 of 326), acne disappeared completely. Seborrhea improved after 12 cycles in 89 of 131 women (67.9%), of whom 76 women (58.0%) were completely cured. Sixty-two serious adverse events (SAE) occurred in 59 of 1655 women. Accidents and injuries of the musculoskeletal system were the SAE with the highest incidence (0.66%). Two cases of deep venous thrombosis, one pulmonary embolism, and two cases of visual disturbances were observed. Only for the two cases of deep venous thrombosis could a relation to Belara be assumed. Of the adverse events commonly reported for oral contraceptives, headache was observed for the first time under study medication in 37.4%, nausea in 23.1%, breast tenderness in 21.7%, and vaginal discharge in 19.4% of the women. The frequency of adverse events decreased with longer duration of a drug consisting of intake of Belara. In conclusion, Belara can be described as an effective and safe oral contraceptive with marked antiandrogenic properties.
PIP: The contraceptive safety and efficacy of long-term use of the oral contraceptive Belara (30 mcg ethinyl estradiol and 2 mg chlormadinone acetate) were assessed in an open, noncontrolled phase III study. Of particular interest was the effect of the anti-androgenic activity of this formulation on clinical signs of androgenization. Belara was taken by 1655 German women (mean age, 25.9 years), for a total of 22,337 cycles. A total of 12 pregnancies occurred, yielding a theoretical Pearl index of 0.269 (95% confidence interval, 0.109-0.600). No withdrawal bleeding occurred in 1655 cycles (7.4%), while spotting was documented in 2565 (11.5%) and breakthrough bleeding in 786 (3.5%). After 12 cycles of use, acne on the face/neck improved in 64.1% of affected women and completely disappeared in 53.4%. Seborrhea improved after 12 cycles in 67.9% of affected women and was cured in 58.0%. Side effects included headache (37.4%), nausea (23.1%), breast tenderness (21.7%), and vaginal discharge (19.4%). Of the 62 serious adverse events reported by 59 women, only the 2 cases of deep venous thrombosis could be linked to Belara use. Overall, these findings suggest that Belara is a well-tolerated oral contraceptive with minor side effects comparable to those associated with use of other low-dose pills.