Elsevier

Fertility and Sterility

Volume 87, Issue 6, June 2007, Pages 1399-1412
Fertility and Sterility

Reproductive endocrinology
A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata

Presented in part during the Annual Meetings of the Society for Gynecologic Investigation (SGI), Washington, DC, March 2003, and Houston, Texas, March 2004.
https://doi.org/10.1016/j.fertnstert.2006.11.094Get rights and content

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.

Section snippets

Study Design and Treatments

This study was prospective, randomized, multicenter, double-blind, and placebo-controlled. All screening evaluations were to be completed within 30 days before the initiation of dosing. Eligible patients were enrolled into the study and randomly assigned to one of three asoprisnil treatment groups (5, 10, and 25 mg) or placebo. A computer-generated central randomization schedule was used to assign each patient in a 1:1:1:1 ratio to the four treatment groups. Study drug was supplied as oral

Demographic Data

A total of 129 premenopausal patients were randomized into the study and received at least one dose of study drug (31 received placebo, 33 received asoprisnil [5 mg], 29 received asoprisnil [10 mg], and 36 received asoprisnil [25 mg]). Overall, there were no important differences in patient demographics across all treatment groups (Table 1). The study population was predominantly Caucasian (73%) and African American (19%). The mean age was 42.6 years (range, 28–50 y), the mean weight was 73.3

Discussion

The results of this double-blind placebo-controlled study demonstrate the clinical potential of asoprisnil for the management of uterine leiomyoma related complaints. A 3-month course of treatment with asoprisnil-controlled uterine bleeding and reduced total uterine volume, as well as that of the dominant leiomyoma. In addition, this treatment was associated with improvements in patient-reported outcomes, including bulk-related symptoms (bloating and pelvic pressure) and global satisfaction

Acknowledgments

The authors thank Gretchen Bodum, R.Ph., for editing the manuscripts and thank Irving Spitz, M.D., for expert comments.

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    Supported by TAP Pharmaceutical Products Inc., Lake Forest, Illinois (clinical trial identifier NCT00160459). Walter Elger, M.D., Ph.D., is a consultant for TAP; all other authors were employees of TAP during the writing of this manuscript.

    1

    Present address for Walter Elger, M.D., Ph.D.: Schorlemerallee, Berlin-Dahlem, Germany

    2

    Present address for Craig A. Winkel, M.D., M.B.A.: Georgetown University, Washington, DC

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