Multicenter, phase III trials on the contraceptive efficacy, tolerability and safety of a new drospirenone‐only pill

Abstract

Introduction Approximately 100 million women currently use combined oral contraceptives. Combined oral contraceptives use is associated with increased risk of venous thromboembolic events and cardiovascular disease. Progestin‐only pills do not increase the risk of venous thromboembolic events, stroke and myocardial infarction but are associated with a poor cycle control. A novel estrogen‐free pill containing only drospirenone (DRSP) was developed to improve bleeding pattern, tolerability and acceptance without increasing venous thromboembolic events risks in contraception. Material and methods Two prospective, multicenter Phase III studies in healthy women aged 18‐45 years were performed to demonstrate the efficacy and safety of a drospirenone‐only pill in a regimen of 24 days of 4 mg of drospirenone tablets followed by 4 days of placebo. A total of 1571 women (14 329 exposure cycles) were analyzed: 713 patients in the 13‐cycle study 1 with 7638 exposure cycles and 858 patients in the 9‐cycle study 2 with 6691 exposure cycles. The primary endpoint was the overall Pearl index, calculated for each study separately, and for both pooled. As main secondary efficacy endpoint, the “method failure Pearl index” including all pregnancies during “perfect medication cycles” was evaluated. EudraCT registration numbers: 2010‐021787‐15 & 2011‐002396‐42. Results Calculations on pooled studies 1 and 2 with 1571 patients gave an overall Pearl index (based on 14 329 cycles) of 0.7258 (95% CI 0.3133 to 1.4301). No single case of deep vein thrombosis or pulmonary embolism and only one case of hyperkalemia were reported. Additional information such as laboratory parameters, body mass index, bodyweight, heart rate and blood pressure showed no statistically significant changes due to the treatment. Conclusions This is the first report of a new drospirenone‐only oral contraceptive providing clinical efficacy similar to combined oral contraceptives, with a good safety profile, and favorable cycle control.

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature

“…In the US study among 915 non-breastfeeding women aged 35 years the Pearl Index was 2.9 (95% CI 1.5, 5.1) [20]. A possible bias for the primary endpoint and the safety aspect including adverse events for all data obtained from the three clinical trials is the discontinuation rate, which was 27.8% and 19.8%, respectively, in the two European studies [18,19] and 65% in the US study [20].…”

“…Efficacy The contraceptive efficacy of 4 mg drospirenone is supported by clinical phase III trials, which included two pivotal European studies [18,19] and one US study [20]. A pooled analysis of the two European studies showed an overall Pearl Index of 0.73 (95% confidence interval [CI] 0.3133, 1.4301) (14,329 cycles of 4 mg drospirenone) and an adjusted Pearl Index of 0.79 (95% CI 0.3410, 1.5562) [19].…”

“…Efficacy The contraceptive efficacy of 4 mg drospirenone is supported by clinical phase III trials, which included two pivotal European studies [18,19] and one US study [20]. A pooled analysis of the two European studies showed an overall Pearl Index of 0.73 (95% confidence interval [CI] 0.3133, 1.4301) (14,329 cycles of 4 mg drospirenone) and an adjusted Pearl Index of 0.79 (95% CI 0.3410, 1.5562) [19]. A pooled analysis of a subgroup of 1251 women aged 35 years showed similar results: an overall Pearl Index (based on 11,145 cycles) of 0.9332 (95% CI 0.4029, 1.8387) and an adjusted Pearl Index (based on 10,173 cycles) of 1.0223 (95% CI 0.4414, 2.0144) [19].…”

“…A pooled analysis of the two European studies showed an overall Pearl Index of 0.73 (95% confidence interval [CI] 0.3133, 1.4301) (14,329 cycles of 4 mg drospirenone) and an adjusted Pearl Index of 0.79 (95% CI 0.3410, 1.5562) [19]. A pooled analysis of a subgroup of 1251 women aged 35 years showed similar results: an overall Pearl Index (based on 11,145 cycles) of 0.9332 (95% CI 0.4029, 1.8387) and an adjusted Pearl Index (based on 10,173 cycles) of 1.0223 (95% CI 0.4414, 2.0144) [19]. The results of both studies reveal that the contraceptive effectiveness of 4 mg drospirenone is similar to that of currently available COCs ( Table 2).…”

“…There were also no reports of arterial thromboembolism, myocardial infarction, stroke or pulmonary embolism (Table 3). It is important to point out that the phase III clinical trials included a significant number of participants with risk factors for VTE [18][19][20]. The recorded risk factors were family history of thromboembolic illness, evidence of predisposing conditions for a vascular or metabolic disease, current smoker >35 years or non-smoker >40 years, and body mass index (BMI) !30 kg/m 2 .…”