HPE HPE 85 – Spring 2017 - Page 56

Practical therapeutics drug among those desiring a long-term medical therapeutic option for fibroids. CDB-4124 (telapristone) A clinical trial (Phase I/II) evaluated the efficacy of telapristone in symptomatic fibroids. This small three-month study, comprising 30 women, compared oral doses of 12.5, 25 and 50mg telapristone with the GnRH analogue leuprolide and a placebo. 37 There was a significant reduction in tumour size and reduced bleeding with telapristone treatment. J-867 (asoprisnil) Studies compared the efficacy and safety of three doses (5, 10 and 25mg and placebo) of asoprisnil in 129 women over 12 weeks. 38,39 Asoprisnil reduced the uterine and fibroid volumes in a dose- dependent manner. There was a dose- dependent decrease in menorrhagia scores in women with menorrhagia at baseline, while amenorrhea rates increased as the dose increased (28.1% with 5mg, 64.3% with 10mg and 83.3% with 25mg), but with no increase in the rates of unscheduled bleeding in all three asoprisnil groups. Results suggested endometrial thickening to be one of the important side effects of the drug. Overall safety data available so far, however, have been reassuring and its impact on bone mineral density, fertility, recurrence rates of fibroids and endometrial hyperplasia are still under evaluation. 2 CDB-2914 (ulipristal acetate) Ulipristal acetate (UA) is the most studied and popular progesterone receptor modulator for treatment of uterine fibroids. 54 Evidence In a trial in which UA was given at 10mg or 20mg against placebo for three cycles, UA showed a 92% reduction in bleeding versus 19% with placebo. 40 Myoma volume was significantly reduced with UA (29% versus 6%; p=0.01). UA eliminated menstrual bleeding and inhibited ovulation (% ovulatory cycles 20% on UA versus 83% with placebo; p=0.001). UA also improved the quality of life subscale. One woman on UA developed endometrial cystic hyperplasia without evidence of atypia. No serious adverse events were reported. 40 A double blind, placebo-controlled trial of efficacy and tolerability has also demonstrated positive results when UA was administered for three to six months, hospitalpharmacyeurope.com showing good control of bleeding, reduction in fibroid size, and improvement in quality of life in the treatment group. 41 Two Phase III clinical trials (PEARL I and II) in Europe demonstrated the efficacy and safety of UA for the treatment of symptomatic uterine fibroids in patients eligible for surgery. 42,43 The PEARL I study, a double blind, placebo- controlled trial, demonstrated reductions in menstrual loss in 91% and greater than 20% reductions in fibroid volume in those taking either 5mg or 10mg of ulipristal acetate for 13 weeks, making it useful in reducing fibroid volume prior to surgery. 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