Dataset Information

Phase III long-term study to evaluate the efficacy and safety of ulipristal acetate in Japanese patients with uterine fibroids.

ABSTRACT:

Aim

To assess the efficacy and safety of long-term intermittent administration of 10-mg ulipristal acetate (UPA) for symptomatic uterine fibroids in Japanese women.

Methods

Open-label, noncomparative study (Japan Primary Registries Network identifier: JapicCTI-173737) conducted at 32 gynecological centers (November 2017-December 2019). Premenopausal women diagnosed with uterine fibroids associated with heavy menstrual bleeding received three 12-week courses of 10-mg UPA once daily. Amenorrhea, fibroid volume, endometrial histology, and safety were assessed.

Results

Of 155 patients enrolled, 140 received ≥1 dose of UPA and were analyzed. Across all courses, the rates of patients with amenorrhea for 35 days were >90%, and >99% of patients achieved uterine bleeding normalization. Median time to amenorrhea after each course started was 4-5 days; menstruation returned after treatment within a median of 25-27 days. Mean changes in fibroid volume from baseline were -21.5%, -31.4%, and -35.0% for Courses 1, 2, and 3, respectively. Patients experienced sustained improvements in anemia, pain, and quality of life during treatment. Most adverse events were mild/moderate in severity and decreased in frequency with each course. Seven serious adverse events (six patients) were reported; anemia, embolic cerebral infarction, and pituitary apoplexy (one patient each) were considered UPA-related. Nonphysiological changes in endometrial histology were transient and benign. No safety concerns were detected in hormone concentrations or liver function tests.

Conclusions

Long-term administration of 10-mg UPA is effective for reducing symptoms associated with uterine fibroids in Japanese women. UPA was well tolerated and few safety concerns were reported.

SUBMITTER: Osuga Y

PROVIDER: S-EPMC8453825 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo assess efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.MethodsThis phase 3, double-blind, placebo-controlled study enrolled premenopausal women (aged 18-50 years) with abnormal uterine bleeding, one or more discrete leiomyomas, and uterine size 20 weeks of gestation or less. Patients were randomized 1:1:1 to 5 mg ulipristal, 10 mg ulipristal, or placebo once daily for 12 weeks followed by 12-week drug-free follow-up. Coprimary endpoints were rate of and time to amenorrhea, defined as no bleeding for the last 35 consecutive days of treatment. Secondary endpoints included rates of amenorrhea from day 11 and change from baseline to endpoint in the Revised Activities subscale of the Uterine Fibroid Symptom and Quality of Life questionnaire, which includes questions pertaining to physical and social activities. Safety assessments included adverse event monitoring and endometrial biopsies. A sample size of 150 was planned to compare separately each dose of ulipristal with placebo.ResultsFrom March 2014 to March 2016, 157 patients were randomized. Demographics were similar across treatment groups. Amenorrhea was achieved by 25 of 53 (47.2% [97.5% CI 31.6-63.2]) and 28 of 48 (58.3% [97.5% CI 41.2-74.1]) patients treated with 5 mg and 10 mg ulipristal, respectively, compared with 1 of 56 (1.8% [97.5% CI 0.0-10.9]) placebo-treated patients (both P<.001). Time to amenorrhea was shorter for both ulipristal doses compared with placebo (P<.001), and both doses of ulipristal resulted in improved quality of life compared with placebo (P<.001). Common adverse events (5% or greater in either ulipristal group during treatment) were hypertension, elevated blood creatinine phosphokinase, and hot flushes. Serious adverse events occurred in four patients, but none was considered related to treatment. Endometrial biopsies were benign.ConclusionUlipristal at 5 mg and 10 mg were well tolerated and superior to placebo in rate of and time to amenorrhea in women with symptomatic uterine leiomyomas.Clinical trial registrationClinicaltrials.gov number, NCT02147197.

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