Efficacy and tolerability of CDB-2914 treatment for symptomatic uterine fibroids: a randomized, double-blind, placebo-controlled, phase IIb study

Abstract

Objective: To evaluate the efficacy and tolerability of the P receptor modulator CDB-2914 (Ulipristal, CDB).

Design: Randomized, placebo-controlled double-blind clinical trial.

Setting: Clinical research center.

Patient(s): Premenopausal women with symptomatic uterine fibroids.

Intervention(s): Once-daily oral CDB (10 or 20 mg) or placebo (PLC) for 12 weeks (treatment 1). A second 3-month treatment with CDB (treatment 2) was offered. A computer-generated blocked randomization was used.

Main outcome measure(s): Magnetic resonance imaging (MRI)-determined total fibroid volume (TFV) change was the primary outcome; amenorrhea and quality of life (QOL) were secondary end points.

Result(s): Treatment 1 TFV increased 7% in the PLC group, but decreased 17% and 24% in the CDB10 and CDB20 groups. The TFV decreased further in treatment 2 (-11%). Amenorrhea occurred in 20/26 women taking CDB and none on PLC. Ovulation resumed after CDB. Hemoglobin improved only with CDB (11.9 ± 1.5 to 12.9 ± 1.0 g/dL) as did the Fibroid QOL Questionnaire symptom severity, energy/mood, and concern subscores, and overall QOL scores. The CDB was well tolerated, with no serious adverse events. Adverse events were unchanged during treatments.

Conclusion(s): Administration of CDB-2914 for 3-6 months controls bleeding, reduces fibroid size, and improves QOL.

Trial registration: ClinicalTrials.gov NCT00290251.

Figure 1

Patient flow through the protocol. Women were enrolled beginning on 3/16/2006. The final magnetic resonance imaging (MRI) of the extension study was obtained on 6/8/09. Ph 2 = treatment 2, Surg = surgery, Myo = myomectomy, Hyster = hysterectomy, Ext = extension study. Reasons for dropping out are provided by superscripts: ^adid not pick up medication; ^bdid not want to have second MRI; ^chad severe headache; ^dhad an out-of-body experience; ^estudy was inconvenient.

Figure 2

Vaginal bleeding during treatment 1. PLC = placebo; CDB = P receptor modulator CDB-2914.

Figure 3

Liver function abnormalities (LFT) in treatments 1 and 2. All abnormal aspartate aminotransferase (AST) (closed squares during treatment; open squares at baseline) and alanine aminotransferase (ALT) (closed circles) results are shown. All women with abnormal values received P receptor modulator CDB-2914. The solid line represents the upper limit of normal for aspartate aminotransferase and the dashed line shows the upper limit of normal for alanine aminotransferase. The number of normal results during the study for each patient is shown at the bottom of the graph. At the end of the study, patient 8 had normal values; patient 9 had values within 3 U/L of the upper limit of normal; all other patients had normal results except for the minor increase in alanine aminotransferase in patients 5 and 7.