What This Study Involves

Uterine leiomyomata (fibroids) are a common benign tumor of the uterine muscle in pre-menopausal women. These tumors may cause bleeding, pelvic pain and pressure. Because fibroids grow in the presence of estrogen, medical therapies that decrease estrogen levels (like GnRH analog) cause fibroids to shrink and so may relieve symptoms. However, such medication can only be given short-term and has inconvenient side effects such as hot-flushes. Thus, many women with symptomatic fibroids choose to have them removed surgically, either individually or by removing the uterus via hysterectomy.

This study evaluates a new medical treatment for fibroids using the progesterone receptor modulator CDB-2914. A similar compound, mifepristone®, reduced fibroid size when given for twelve weeks. This study will compare fibroid size, hormone levels and symptoms before and during daily administration of CDB-2914 (10 or 25 mg) or placebo for 10 – 14 weeks. To do this, women will undergo MRI and a saline hysterosonogram (ultrasound with fluid) of the uterus before and at the end of the treatment; they will have blood drawn every 7 – 14 days, and will fill out a symptom calendar at home. Hysterectomy will be performed at the end of the treatment to evaluate the effects of the medication on the uterine and fibroid tissues, and to provide treatment for the study participant. Women will be randomly assigned to the treatment groups; during the treatment period neither the participants nor the investigators will know the type of treatment that a woman receives.

The study takes about 5-months, from baseline screening to the end of an average recovery time following the hysterectomy. The first month is a baseline cycle during which we establish that the patient is healthy and fulfills the study requirements. She then begins taking the study drug for about 3 months, after which receives a complete abdominal hysterectomy.

• Screening visit at the NIH. The patient comes in for a physical examination and laboratory results so we can be sure she is healthy. If she meets the requirements, she enrolls in the protocol.
  
• Baseline cycle. As the woman’s next menses (period) she begins filling out a symptom calendar and monitoring her LH surge using a home kit that we provide. She fills out the calendar and does the LH surge kit again every month until she has completed the study.
  • Imaging studies: MRI (Magnetic Resonance Imaging), a vaginal ultrasound, and a sonohysterogram are done at the NIH.
  • This month, and each month following, the woman provides a blood sample 6 to 8 days after her LH.
    
• First treatment cycle begins the next time the woman’s menses comes.
  • On the first or second day of her period she comes in for a urine pregnancy test and to pick up the study drug. Contingent upon a negative pregnancy result she begins taking the study drug once every day up to and including the day of the hysterectomy.
  • Six to eight days before and then again after her LH surge the woman provides a blood sample for safety and study-related bloods. She will also provide a 24-hour urine specimen.
    
• Second treatment cycle begins with the next menses.
  • We repeat the pregnancy test, blood work before and after the LH surge, urine collection, and home monitoring.
    
• Third treatment cycle begins with the next menses.
  • For this final cycle the procedures are the same as the first and second cycles, except the woman also receives an MRI, vaginal ultrasound and hysterosonogram and a pre-operative appointment.
  • The hysterectomy occurs 90 to 102 days after the woman begins taking the study drug. The average time of the hospital stay after the operation is 5 days and complete recovery from usually takes six to eight weeks. During this time the woman comes to a post-operative visit to the NIH and, if she did not have her ovaries removed during the operation (an optional procedure), she is asked to monitor her LH surge so that we can make sure she is cycling normally.