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

NCT00290251 | Completed Phase 2 Results DMC

• 3 other identifiers: 0600901ZIAHD000637-1706-CH-0090
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Leiomyoma

Keywords

Endometrium; Progesterone; Estrogen; Fibroid; Hysterectomy; Leiomyoma; Uterine Fibroids; Fibroids

Outcome Measures

Primary Outcomes (1)

• Shrinkage of Fibroids - Size of Fibroids

  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.

  3 months (baseline to end of treatment)

Secondary Outcomes (1)

• Short Form-36 and Uterine Fibroid Symptom Quality of Life

  3 months (Baseline to end of treatment 1)

Study Arms (6)

ulipristal acetate -20 mg

ACTIVE COMPARATOR

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

Drug: ulipristal acetate 20 mg

ulipristal acetate - 10 mg

ACTIVE COMPARATOR

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

Drug: ulipristal acetate 10 mg

Placebo

PLACEBO COMPARATOR

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

Drug: placebo

Pre-ulipristal acetate 10 mg

NO INTERVENTION

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

Pre-ulipristal acetate 20 mg

NO INTERVENTION

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

Pre-placebo

NO INTERVENTION

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

Interventions

ulipristal acetate 20 mg DRUG

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

Also known as: VA2914; CDB-2914

ulipristal acetate -20 mg

ulipristal acetate 10 mg DRUG

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

Also known as: VA2914; CDB2914

ulipristal acetate - 10 mg

placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female gender-to evaluate effects in the target population for clinical trials.
• History of uterine leiomyoma causing symptoms of bleeding, pressure, or pain, as defined by the American College of Obstetrics and Gynecology (ACOG) practice bulletin:
• 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;
• 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.
• 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 (for those wishing surgery); iron may be administered to improve red blood cell counts.
• Willing and able to comply with study requirements.
• Age 25 to 50.
• Using mechanical (condoms, diaphragms) sterilization or abstinence methods of contraception for the duration of the study.
• Negative urine pregnancy test.
• Body mass index (BMI) less than or equal to 33, if a surgical candidate or less than or equal to 35, if not a surgical candidate.
• Creatinine less than 1.3 mg/dL.
• Liver function tests within 130% of upper limit.

You may not qualify if:

• Significant abnormalities in the history, physical or laboratory examination.
• Pregnancy.
• Lactation.
• Use of oral, injectable or inhaled glucocorticoids or megestrol 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 induce hepatic P450 enzymes; use of imidazoles.
• Current use of Gonadotropin-releasing hormone (GnRH) analogs or other compounds that affect menstrual cyclicity.
• Follicle stimulating hormone (FSH) greater than 20 IU/mL.
• Untreated cervical dysplasia.
• Need for interval use of narcotics.
• Abnormal adnexal/ovarian mass.
• Use of herbal medication having estrogenic or antiestrogenic effects within the past 3 months.
• Contradiction to anesthesia, for women planning surgery.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• HRA Pharma: collaborator

Study Sites (2)

NIH Clinical Center

Bethesda, Maryland, 20891, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• Batista MC, Cartledge TP, Zellmer AW, Merino MJ, Axiotis C, Loriaux DL, Nieman LK. Delayed endometrial maturation induced by daily administration of the antiprogestin RU 486: a potential new contraceptive strategy. Am J Obstet Gynecol. 1992 Jul;167(1):60-5. doi: 10.1016/s0002-9378(11)91627-5.

  PMID: 1442957 BACKGROUND

• Burroughs KD, Howe SR, Okubo Y, Fuchs-Young R, LeRoith D, Walker CL. Dysregulation of IGF-I signaling in uterine leiomyoma. J Endocrinol. 2002 Jan;172(1):83-93. doi: 10.1677/joe.0.1720083.

  PMID: 11786376 BACKGROUND

• Cadepond F, Ulmann A, Baulieu EE. RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med. 1997;48:129-56. doi: 10.1146/annurev.med.48.1.129.

  PMID: 9046951 BACKGROUND

• Levens ED, Wesley R, Premkumar A, Blocker W, Nieman LK. Magnetic resonance imaging and transvaginal ultrasound for determining fibroid burden: implications for research and clinical care. Am J Obstet Gynecol. 2009 May;200(5):537.e1-7. doi: 10.1016/j.ajog.2008.12.037. Epub 2009 Mar 9.

  PMID: 19268886 BACKGROUND

• Nieman LK, Blocker W, Nansel T, Mahoney S, Reynolds J, Blithe D, Wesley R, Armstrong A. Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study. Fertil Steril. 2011 Feb;95(2):767-72.e1-2. doi: 10.1016/j.fertnstert.2010.09.059. Epub 2010 Nov 5.

  PMID: 21055739 BACKGROUND

• Parikh TP, Malik M, Britten J, Aly JM, Pilgrim J, Catherino WH. Steroid hormones and hormone antagonists regulate the neural marker neurotrimin in uterine leiomyoma. Fertil Steril. 2020 Jan;113(1):176-186. doi: 10.1016/j.fertnstert.2019.08.090.

  PMID: 32033718 DERIVED

• Lewis TD, Malik M, Britten J, Parikh T, Cox J, Catherino WH. Ulipristal acetate decreases active TGF-beta3 and its canonical signaling in uterine leiomyoma via two novel mechanisms. Fertil Steril. 2019 Apr;111(4):806-815.e1. doi: 10.1016/j.fertnstert.2018.12.026. Epub 2019 Mar 11.

  PMID: 30871768 DERIVED

• Ng SSM, Jorge S, Malik M, Britten J, Su SC, Armstrong CR, Brennan JT, Chang S, Baig KM, Driggers PH, Segars JH. A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine Fibroid Cells. J Clin Endocrinol Metab. 2019 Mar 1;104(3):970-980. doi: 10.1210/jc.2018-01216.

  PMID: 30239831 DERIVED

• Levens ED, Potlog-Nahari C, Armstrong AY, Wesley R, Premkumar A, Blithe DL, Blocker W, Nieman LK. CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial. Obstet Gynecol. 2008 May;111(5):1129-36. doi: 10.1097/AOG.0b013e3181705d0e.

  PMID: 18448745 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leiomyoma

Interventions

ulipristal acetate; ulipristal

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Lynnette Nieman MD
• Organization: NICHD, NIH

NiemanL@nih.gov

301-496-8935

Study Officials

• Lynnette K Nieman, MD

  NICHD, NIH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: study agents were formulated in identical looking capsules
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: February 10, 2006
• First Posted: February 10, 2006
• Study Start: February 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: August 1, 2010
• Last Updated: July 15, 2024
• Results First Posted: December 18, 2012

Record last verified: 2024-07

Locations

US (2)