This study will evaluate the selective progesterone receptor modulator CDB-2914 for treating uterine fibroids in pre-menopausal women. It will compare fibroid size, hormone levels and symptoms in women who take CDB-2914 with that of women who take a placebo (an inactive substance). The study will also evaluate the endocrine effects of chronic daily administration of CDB-2914, including possible effects on the menstrual cycle and on adrenal gland function.

Pre-menopausal women between 33 and 50 years of age who have predictable menstrual cycles of normal length and uterine fibroids of at least 2 cm in size may be eligible for this study. Only women who need and want hysterectomy for treatment of fibroids will be enrolled. Candidates will be screened with a medical history and physical examination, including a breast and pelvic examination, blood and urine tests, and completion of a questionnaire about quality of life. They will be taught to use a kit to test their urine for LH, a hormone produced in large amounts just before ovulation, and will be given a calendar to record the LH surge, as well as any spotting, bleeding, or other symptoms. The study will take place over four menstrual cycles, after which hysterectomy will be performed. Participants will undergo the following procedures:

- First (pre-treatment) cycle: Participants will undergo magnetic resonance imaging (MRI) and a special ultrasound test called saline hysterosonogram. MRI uses radio waves and a magnetic field to image body tissues. The subject lies in a narrow metal cylinder (the scanner) for about an hour during the imaging. A contrast material is injected into a vein to brighten the images. The saline hysterosonogram involves placing a speculum in the vagina, as if for a Pap test, and then putting a very small amount of liquid inside the uterus, using a small plastic tube. An ultrasound examination is then done by inserting a probe into the vagina. The probe emits and receives sound waves that are used to form a picture of the internal structures.

- Second through fourth menstrual cycles - Participants will have a pregnancy test on the first or second day of each cycle. Those who are not pregnant will take CDB-2914 once a day for three menstrual cycles, or up to 102 days if the cycles are irregular. At specific times during the cycles, subject will have blood tests to measure the effect of CDB-2914 on hormones, blood count, blood chemistries, and liver function, and ultrasound tests to check the number and size of follicles in the ovaries. They will test their urine to detect the LH surge and will have additional hormone blood tests. At three times during the study-during the first, second and third menstrual cycles-subjects will bring a 24-hour urine collection to the clinic for measurements of cortisol and adrenal gland function. A transvaginal ultrasound study will be repeated after 4 to 6 weeks of treatment to check fibroid growth. A repeat saline hysterosonogram and MRI will be done within 2 weeks of surgery to count the number of fibroids and measure their size.

Women who have completed the study to the end of the four menstrual cycles and still require hysterectomy will stop taking CDB-2914. They will complete another quality of life questionnaire. Their blood levels of CDB-2914 will be measured, and they will have a hysterectomy, in which the uterus, and possibly the ovaries, will be removed. Subjects will be discharged from the hospital 2 to 4 days after surgery and will return to the clinic for post-operative evaluation after 4 to 6 weeks.

Condition	Treatment or Intervention	Phase
Leiomyoma	Drug: CDB-2914	Phase II

Further Study Details: 

Expected Total Enrollment:  90

Uterine leiomyomata (fibroids) are a common benign tumor of the uterine muscle in premenopausal 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.

The study evaluates a new medical treatment for fibroids using the progesterone receptor modulator CDB-2914. A similar compound, mifepristone (Registered Trademark), 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.

This study will be the first to evaluate the endocrine effects of chronic administration of CDB-2914 in pre-menopausal women. CDB-2914 has been given daily for 42 days to post-menopausal women without adverse side effects. While the amount of CDB-2914 proposed in this study did not affect the menstrual cycle when given as a single dose, it is possible that daily doses will have an effect on development of the follicle (egg). To evaluate this possibility, we will measure blood hormone levels and obtain ultrasound examinations of the ovaries in healthy women.

Genders Eligible for Study:  Female

Criteria

GENERAL INCLUSION CRITERIA:
Women receiving insulin or thyroid hormone replacement may participate if well-controlled; use of vitamins and calcium under RDA is allowed.
Female gender-to evaluate effects in the target population for clinical trials.
In good health. Chronic medication use is acceptable except for glucocorticoid use. Other chronic medication use may be acceptable at the discretion of the research team. Interval use of over-the counter drugs is acceptable but must be recorded.
Menstrual cycles of 24 - 35 days.
Hemoglobin greater than 10 g/dL.
Willing and able to comply with study requirements.
Age 33 to 50.
Using mechanical (condoms, diaphragms), sterilization or abstinence methods of contraception for the duration of the study.
Negative urine pregnancy test.
BMI less than or equal to 33.
Able to read and speak English fluently to allow accurate self-administration of medication, recording of symptoms and unassisted completion of questionnaire.
Normal glomerular filtration rate.
Liver function tests within 130% of upper limit.
INCLUSION CRITERIA FOR WOMEN WITH LEIOMYOMA:
History of uterine leiomyoma causing symptoms of bleeding, pressure, or pain, as defined by the ACOG practice bulletin (ACOG Practice Bulletin 1994):
Excessive uterine bleeding will be evidenced by either of the following-profuse bleeding with flooding or clots or repetitive periods lasting for more than 8 days; or anemia due to acute or chronic blood loss; OR
Pelvic discomfort caused by leiomyomata, either acute and severe or chronic lower abdominal or low back pressure or bladder pressure with urinary frequency not due to urinary tract infection.
Uterine leiomyoma(ta) of at least 2 cm size.
No desire for fertility; willing to undergo hysterectomy.
GENERAL EXCLUSION CRITERIA:
Significant abnormalities in the history, physical or laboratory examination.
Pregnancy.
Lactation.
Use of oral, injectable or inhaled glucocorticoids or megesterol within the last year.
Unexplained vaginal bleeding.
History of malignancy within the past 5 years.
Use of estrogen or progesterone-containing compounds, such as oral contraceptives and hormone replacement therapy, within 8 weeks of study entry, including transdermal, injectable, vaginal and oral preparations.
Use of agents known to induct hepatic P450 enzymes; use of imidazoles.
Current use of GnRH analogs or other compounds that affect menstrual cyclicity.
FSH greater than 20 IU/mL.
Significant medical disorders.
Cervical dysplasia.
Need for interval use of narcotics.
Abnormal adnexal/ovarian mass.
Intrauterine device.
EXCLUSION CRITERIA FOR WOMEN WITH FIBROIDS:
Use of herbal medication having estrogenic or antiestrogenic effects within the past 3 months.
Contradiction to anesthesia
Genetic causes of leiomyomata.
Previous participation in the study.
Known recent rapid growth of fibroids, defined as a doubling in size in six months.

Maryland
      National Institute of Child Health and Human Development (NICHD), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020287; 02-CH-0287
Record last reviewed:  August 11, 2004
Last Updated:  December 1, 2004
Record first received:  September 5, 2002
ClinicalTrials.gov Identifier:  NCT00044876
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08