A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata.
OBJECTIVE
To determine efficacy and safety of asoprisnil in patients with leiomyomata.


METHODS
Phase 2, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study.


METHODS
Twenty-eight sites in the United States and 1 in Canada.


METHODS
One hundred twenty-nine women with leiomyomata.


METHODS
Asoprisnil (5, 10, or 25 mg) or placebo orally daily for 12 weeks.


METHODS
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.


RESULTS
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.


CONCLUSIONS
After 12-week treatment, asoprisnil controlled uterine bleeding while reducing leiomyoma volume and the associated pressure symptoms. Asoprisnil was well tolerated.
Chwalisz
Kristof
K
TAP Pharmaceutical Products Inc., Lake Forest, Illinois 60045, USA. kristof.chwalisz@tap.com
Larsen
Lois
L
Mattia-Goldberg
Cynthia
C
Edmonds
Anthony
A
Elger
Walter
W
Winkel
Craig A
CA
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D004963:Estrenes / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy*; D008875:Middle Aged; D010091:Oximes / Q000627:therapeutic use* / Q000633:toxicity; D010120:Oxytocics / Q000627:therapeutic use*; D018579:Patient Selection; D010919:Placebos; D011980:Receptors, Progesterone / Q000187:drug effects / Q000502:physiology*; D014592:Uterine Hemorrhage / Q000453:epidemiology; D014594:Uterine Neoplasms / Q000188:drug therapy*
D004963:Estrenes; D010091:Oximes; D010120:Oxytocics; D010919:Placebos; D011980:Receptors, Progesterone; C488516:asoprisnil