OBJECTIVE: To determine efficacy and safety of asoprisnil in patients with leiomyomata.
DESIGN: Phase 2, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study.
SETTING: Twenty-eight sites in the United States and 1 in Canada.
PATIENT(S): One hundred twenty-nine women with leiomyomata.
INTERVENTION(S): Asoprisnil (5, 10, or 25 mg) or placebo orally daily for 12 weeks.
MAIN OUTCOME MEASURE(S): Uterine bleeding changes by using daily bleeding diaries, hemoglobin concentrations, dominant leiomyoma and uterus volume measured sonographically, patient-reported symptoms related to bloating and pelvic pressure, endometrial thickness and morphology, hormonal parameters, and standard safety measures.
RESULT(S): Asoprisnil suppressed uterine bleeding in 28%, 64%, and 83% of subjects at 5, 10, and 25 mg, respectively, and reduced leiomyoma and uterine volumes. Median percentage decrease from baseline in leiomyoma volume was statistically significant at 25 mg compared with placebo after 4 and 8 weeks of treatment; by week 12, leiomyoma volume was reduced by 36%. There was a significant reduction in bloating with the two highest doses and in pelvic pressure with 25 mg by week 12. Asoprisnil was associated with follicular-phase estrogen concentration and minimal hypoestrogenic symptoms.
CONCLUSION(S): After 12-week treatment, asoprisnil controlled uterine bleeding while reducing leiomyoma volume and the associated pressure symptoms. Asoprisnil was well tolerated.
OBJECTIVE: The menstrual pictogram (MP), a semiquantitative, easy-to-use tool to assess blood loss, was validated against the reference standard of alkaline hematin (AH) quantitation using data pooled from 3 clinical trials.
METHODS: Premenopausal women aged ≥18 years with heavy menstrual bleeding (HMB) associated with uterine leiomyomata were randomized to asoprisnil (10 or 25 mg) or placebo. Patients completed the MP and collected feminine hygiene products for assessment of blood loss by the AH method. Agreement between the MP and the AH method was calculated.
RESULTS: The positive predictive value of the MP total to distinguish women with HMB against the AH total was 91%. The agreement (κ-statistic) between AH and MP totals for classifying patients with ≥50% or <50% decreases in HMB was 0.88 (95% confidence interval [CI], 0.78-0.98), and the MP was 96% sensitive and 92% specific. The methods showed good association for percentage change in blood (intraclass correlation coefficient [ICC] of 0.86, 95% CI, 0.80-0.91) but not for actual blood loss per cycle (ICC of 0.64, [95% CI, 0.55-0.71]); the greatest underestimation occurred for severely stained napkins.
CONCLUSION: In this study, the MP distinguished women with HMB and adequately assessed improvements with therapy.
