Neoplasms

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Skin and Connective Tissue Diseases

Leiomyoma

Myofibroma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

All Drugs and Chemicals

Reproductive Control Agents

Estrogens

Progesterone

Ulipristal acetate

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

20 mg daily dose ulipristal acetate for three menstrual cycles or up to 102 days

10 mg daily dose ulipristal acetate for three menstrual cycles or up to 102 days

Placebo taken daily for three menstrual cycles or up to 102 days

Subjects were studied during one baseline cycle without any intervention before entering ulipristal acetate 10 mg arm

Subjects were studied during one baseline cycle without any intervention before entering ulipristal acetate 20 mg arm

Subjects were studied during one baseline cycle without any intervention before entering placebo arm

ulipristal acetate at a daily dose of 20 mg, given once daily for three menstrual cycles or 90 - 102 days if amenorrheic

ulipristal acetate 20 mg

10 mg given daily for three menstrual cycles or 90 - 102 days

ulipristal acetate 10 mg

placebo given once daily for 3 menstrual cycles or 90 - 102 days

placebo

Lynnette K Nieman, MD

This study will evaluate whether the experimental drug ulipristal acetate can shrink uterine fibroids in pre-menopausal women.

Uterine leiomyomata (fibroids) are a common benign tumor of the uterine muscle in pre-menopausal women that may cause bleeding, pelvic pain and pressure. Because fibroids grow in the presence of estrogen, medical therapies that decrease estrogen levels (like Gonadotropin releasing hormone,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-flashes. Thus, many women with symptomatic fibroids choose to have them removed surgically, either individually or by removing the uterus via hysterectomy.

Women between 25 and 50 years of age who have regular menstrual cycles and a history of uterine fibroids that cause heavy bleeding, pressure, or pain may be eligible for this study. Candidates are screened with a medical history and physical examination, including breast and pelvic examination, blood and urine tests, a quality-of-life questionnaire, and a home urine test for leuteinizing hormone (LH) surge. They are given a diary to record the LH surge, days of vaginal spotting or bleeding, and symptoms. Participation includes the following:

Baseline Studies (First Menstrual Cycle)

* Magnetic resonance imaging (MRI): The subject lies in the MRI scanner, a narrow cylinder with a strong magnetic field, for imaging the uterus.
* Saline hysterosonogram: This is an ultrasound examination of the uterus. A speculum is placed in the vagina and a small amount of liquid is inserted into the uterus. A probe is then inserted into the vagina. The probe emits and receives sound waves that are used to visualize the fibroids and surrounding structures.

Study Drug Phase (Second through Fourth Menstrual Cycles)

* Subjects are randomly assigned to take ulipristal acetate or placebo (inactive compound) once a day by mouth on an empty stomach for three menstrual cycles or up to 102 days if menstrual cycles are irregular or stop.
* Pregnancy test on first or second day of every menstrual cycle.
* Blood tests every 2 weeks to measure effects of study medication on hormones, blood count, blood chemistries and liver function.
* 24-hour urine collections three times during the study, about once a month, to measure cortisol and check adrenal gland function.
* Repeat transvaginal ultrasound after 4-6 weeks of study drug to check fibroid growth.
* Repeat hysterosonogram and MRI within 2 weeks of surgery to count and measure the fibroids. or placebo (inactive compound) once a day by mouth on an empty stomach for three menstrual cycles or up to 102 days if menstrual cycles are irregular or stop.
* Pregnancy test on first or second day of every menstrual cycle.
* Blood tests every 2 weeks to measure effects of study medication on hormones, blood count, blood chemistries and liver function.
* 24-hour urine collections three times during the study, about once a month, to measure cortisol and check adrenal gland function.
* Repeat transvaginal ultrasound after 4-6 weeks of study drug to check fibroid growth.
* Repeat hysterosonogram and MRI within 2 weeks of surgery to count and measure the fibroids. or placebo (inactive compound) once a day by mouth on an empty stomach for three menstrual cycles or up to 102 days if menstrual cycles are irregular or stop.
* Pregnancy test on first or second day of every menstrual cycle.
* Blood tests every 2 weeks to measure effects of study medication on hormones, blood count, blood chemistries and liver function.
* 24-hour urine collections three times during the study, about once a month, to measure cortisol and check adrenal gland function.
* Repeat transvaginal ultrasound after 4-6 weeks of study drug to check fibroid growth.
* Repeat hysterosonogram and MRI within 2 weeks of surgery to count and measure the fibroids.

Subjects were studied during a single baseline menstrual cycle followed by a cross-over into three arms (active treatment at one of two doses, or placebo) given for three menstrual cycles

study agents were formulated in identical looking capsules

Treatment of Uterine Fibroids With the Selective Progesterone Receptor Modulator CDB-2914

Evaluation of Whether the Selective Progesterone Receptor Modulator CDB-2914 Can Shrink Leiomyomata

The primary outcome, fibroid volume, was calculated by an ellipsoid formula (π/6xd1xd2xd3) using orthogonal three-dimensional measurements taken from pelvic MRI scan. Individual volumes were summed to assess total fibroid volume for each woman, which were log-transformed before analysis. Women with paired MRI results were included in this intent to treat analysis, even if they did not take all study medication. Fibroids were included if they were seen on both studies.The absolute change in cm3 between baseline and end of treatment was calculated and its log was used for statistics and reporting the results in the data table below.

The short form-36 (SF-36)and Uterine Fibroid Symptom Quality of Life (UFS-QOL) questionnaires were given before and at treatment end with scales of 0 - 100. SF-36 scales = mental and physical well-being. The UFS subscales are symptom severity, concern, activities, energy and mood, control, self-consciousness, sexual functioning compiled into an overall QOL score. Higher results indicate better QOL on all but symptom severity (higher = worse). The change in scores from baseline to end of treatment was calculated.

HRA Pharma

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Women recorded specific adverse events on a calendar; there was also a write-in field. The number of women with at least one day of each symptom is reported.

Women received ulipristal acetate at a daily dose of 20 mg for 90 - 102 days or three menstrual cycles.

Ulipristal Acetate -20mg

Women received ulipristal acetate at a daily dose of 10 mg for 90 - 102 days or three menstrual cycles.

Ulipristal Acetate- 10 mg

Women received placebo capsules for 90 - 102 days or three menstrual cycles.

Placebo

Women charted symptoms for one menstrual cycle before entering ulipristal acetate 20 mg group

Pre-Ulipristal Acetate 20 mg

Women charted symptoms for one menstrual cycle before entering ulipristal acetate 10 mg group

Pre-Ulipristal Acetate- 10 mg

Women charted symptoms for one menstrual cycle before entering placebo group

Pre-Placebo

All women who received Ulipristal Acetate - 20 mg

Ulipristal Acetate 10 mg

Ulipristal Acetate 20 mg

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Lynnette Nieman MD

Ulipristal acetate groups one and two were first compared and found to be similar (see statistical analysis 1), so they were combined into a single treatment group for comparison to placebo group

Women received ulipristal acetate at 20 mg/day for 90 - 102 days or three menstrual cycles.

Women received ulipristal acetate at 10 mg/day for 90 - 102 days or three menstrual cycles.

Ulipristal Acetate - 10 mg

Per protocol, including women with two MRIs regardless of whether they took all study medication. The two ulipristal acetate arms, 10 mg and 20 mg, were not different from each other (see statistical analysis 1) so they were combined for analysis of outcomes (in statistical analysis 2).

Shrinkage of Fibroids - Size of Fibroids

SF-36 Physical Component

SF-36 Mental Component

UFS Symptom Severity Score

UFS Overall health related quality of life

UFS Concern subscore

UFS Energy/mood subscore

UFS Control subscore

UFS self-conscious subscore

UFS sexual function subscore

UFS activities subscore

UFS composite bleeding subscore

Women received ulipristal acetate at a daily dose of 10 or 20 mg for 90 - 102 days or three menstrual cycles.

Ulipristal Acetate -10 and 20mg

All completers received a questionnaire at the end of the three-month study. One woman in the placebo group did not complete the questionnaire. All women receiving ulipristal acetate were combined for analysis of QOL, to parallel the combined analysis done for the primary outcome measure.

Short Form-36 and Uterine Fibroid Symptom Quality of Life

Women received no intervention for one menstrual cycle before entering ulipristal acetate 20 mg group

Pre-ulipristal Acetate - 20 mg

Pre-ulipristal Acetate 10 mg

Women received no intervention for one menstrual cycle before entering placebo group

Spots Global Cancer Trial Database for ulipristal acetate 20 mg