Ulipristal acetate for Japanese women with symptomatic uterine fibroids: A double‐blind, randomized, phase II dose‐finding study

Abstract

PurposeA multicenter, randomized, double‐blind, placebo‐controlled trial was conducted to evaluate the efficacy, safety, and appropriate dose of ulipristal acetate (UPA) in Japanese women with symptomatic uterine fibroids (UFs).MethodsA total of 121 premenopausal women with UFs were enrolled to receive either placebo, UPA‐2.5 mg, UPA‐5 mg, UPA‐10 mg, or leuprorelin acetate (LEU), a reference drug, for 12 weeks. The primary end point was the rate of patients having achieved amenorrhea for 35 days at Week 12.ResultsThe rates for amenorrhea were 4.5%, 60.0%, 72.7%, 88.0%, and 76.2% in the placebo, UPA‐2.5 mg, UPA‐5 mg, UPA‐10 mg, and LEU groups, respectively. The median times to amenorrhea were 20.0, 5.0, 5.0, and 23.0 days for treatment with UPA‐2.5 mg, UPA‐5 mg, UPA‐10 mg, and LEU, respectively. A significant dose‐response of UPA for the rate of amenorrhea was observed. The overall incidence rates of adverse events were 45.8% in the placebo group, 56.5%‐80.0% in the UPA groups, and 100.0% in the LEU group. There were no notable safety issues with UPA.ConclusionsUlipristal acetate was effective and well tolerated in Japanese women with UFs. The recommended dose of UPA is considered to be 10 mg.

Ulipristal acetate compared with leuprorelin acetate for Japanese women with symptomatic uterine fibroids: a phase III randomized controlled trial

“…In this study, the mean age of the UPA group was 43 years, similar to that of other studies in which 10 mg of UPA was administered (Japanese phase II study (24), 41.1 years; PEARL I study (18), 42 years; and VENUS I study (21), 41.3 years). The mean BMI of the UPA group was 22.3 kg/m 2 , similar to that of the Japanese phase II study (22.6 kg/m 2 ) (24) but lower than that of the PEARL I study (25.0 kg/m 2 ) (18) and VENUS I study (32.1 kg/m 2 ) (21).…”

“…The rate of amenorrhea in the UPA group (87.0%) was equivalent to that found for the UPA 10-mg group in the phase II study (24) in Japan (88.0%). The rate of uterine bleeding normalization (94.8%) in our study, using the same uterine bleeding criteria, was comparable to that of the PEARL I (92%) and PEARL II (98%) studies (17,18).…”

“…In the PEARL I and II studies, the uterine bleeding control rate, the primary endpoint, was not much different between the UPA dose of 5 mg and 10 mg (PEARL I, 91% for 5 mg, 92% for 10 mg; PEARL II, 90% for 5 mg, 98% for 10 mg) (17,18). On the other hand, in a phase II dose-finding study of UPA in Japan, 3 doses were evaluated, and dose dependency was observed for the rate of causing amenorrhea (60.0% for 2.5 mg, 72.7% for 5 mg, and 88.0% for 10 mg; P< .0001), the primary endpoint, and there were no differences in the safety data (24). Therefore, 10 mg was set as the recommended dose in this study.…”

“…Regarding the LEU group, the rate of change was À42.1% AE 19.0% for 1.88 mg and À49.0% AE 28.8% for 3.75 mg. The median time [95% CI] taken for menstrual recovery was significantly shorter in the UPA group (27 [23][24][25][26][27][28][29][30] days) than in the LEU group (56 [53-60] days) (log-rank test, P< .0001). The rate of change in the UF volume at 12 weeks was significantly higher in the LEU group (À43.2%) than in the UPA group (À23.7%) ( Table 2); however, during the follow-up period at week 24, there was no significant difference between the groups.…”

“…The rate of AEs was 56.5% for 2.5 mg, 73.9% for 5 mg, and 80.0% for 10 mg, showing no apparent difference in safety among the doses. Therefore, the recommended dose of UPA for Japanese patients was determined to be 10 mg (24). Based on these results, a phase III study was conducted to evaluate the efficacy and safety of the 10-mg dosage of UPA compared with leuprorelin acetate (LEU), a GnRH agonist, in Japanese patients with UFs.…”