Efficacy and safety of desogestrel/ethinylestradiol 150/20 flexible extended regimen (FREEDOM 150/20) in dysmenorrhea: phase 3 study in Japan

Abstract

Objective

To evaluate the efficacy and long-term safety of a user-driven flexible extended regimen of desogestrel 150 μg/ethinylestradiol 20 μg (DSG/EE 150/20) for the treatment of primary or secondary dysmenorrhea in women from Japan.

Design

Phase 3, randomized, placebo-controlled, parallel-group, double-blind study with an open-label extension period.

Subjects

Two hundred and eleven women with regular menstrual cycles and primary or secondary dysmenorrhea in 21 centres across Japan.

Intervention

Participants were randomly assigned (3:1) to receive DSG/EE 150/20 μg or placebo once daily for 24–80 consecutive days, with each treatment period followed by a 4-day tablet-free interval. After the double-blind phase (three 28-day cycles), participants entered an open-label phase (≤10 cycles); participants initially receiving placebo were switched to DSG/EE.

Main Outcome Measures

Primary endpoint was change from baseline through day 84 in total dysmenorrhea score (TDS). Secondary endpoints included number of days with dysmenorrheic pain, patient global impression of change (PGI-C), treatment satisfaction questionnaire for medication (TSQM-9), quality of life (QoL) measured by the 36-item short form health survey version 2.0 (SF-36v2), and safety outcomes.

Results

In the 211 participants randomized to DSG/EE (n = 159) and placebo (n = 52), the mean (SD) age was 32.3 (7.56) years, and body mass index was 21.94 (3.18). A significant reduction in TDS from baseline through day 84 was observed in the DSG/EE group vs. placebo (least squares mean: −2.50 vs. −0.84; treatment difference [95% confidence interval: −1.67 [−2.08, −1.26]). The number of days with mild, moderate, and severe pain were 12.9 vs. 12.1, 4.8 vs. 6.5, and 0.8 vs. 1.1 days in the DSG/EE vs. placebo group. Over 80% of DSG/EE-treated participants reported improvement in PGI-C scores compared with <30% on placebo. TSQM-9 global satisfaction and effectiveness least squares mean scores were higher with DSG/EE (63.69 vs. 36.62 and 62.86 vs. 35.5) compared with placebo. DSG/EE improved SF-36v2 scores, particularly in the physical component summary, bodily pain, and role-physical domains. Overall, the most frequent treatment-emergent adverse events were intermenstrual bleeding, nasopharyngitis, and nausea. No deaths were reported during the entire study period.

Conclusion

DSG/EE 150/20 effectively reduced dysmenorrhea severity, improved SF-36v2 scores and treatment satisfaction, offered dosing flexibility, and was well-tolerated with a safety profile consistent with combined oral contraceptives.

Trial Registration

jRCT2031230276 (https://jrct.mhlw.go.jp/en-latest-detail/jRCT2031230276)