Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study.

OBJECTIVE: To evaluate the safety and efficacy of elagolix vs. placebo and elagolix with low-dose E2/progestogen add-back therapy. DESIGN: Proof-of-concept, dose-ranging, multiple-cohort study. SETTING: Clinics. PATIENT(S): Premenopausal women with fibroids and heavy menstrual bleeding (menstrual blood loss [MBL] >80 mL per cycle). INTERVENTION(S): Three months' treatment with elagolix alone: 100 mg twice daily (BID), 200 mg BID, 300 mg BID, 400 mg once daily (QD), or 600 mg QD (all but the 600 mg QD arm were placebo controlled); or elagolix plus add-back therapy: 200 mg BID plus continuous low-dose E2 0.5 mg/norethindrone acetate 0.1 mg or elagolix 300 mg BID plus E2 1 mg continuously and cyclical P 200 mg. MAIN OUTCOME MEASURE(S): Least-squares mean percentage change in MBL; adverse events (AEs). RESULT(S): Mean age was 41.8 years; 73.8% were black; mean baseline MBL was 267 mL. Of randomized women (elagolix alone, n = 160; placebo, n = 50; elagolix with add-back therapy, n = 61), 228 of 271 completed the 3-month treatment period. The MBL percentage change from baseline to last 28 days was significantly greater with elagolix alone (range, -72% to -98%; dose-dependent reduction was highest with 300 mg BID) vs. placebo (range, -8% to -41%); mean percentage changes with add-back regimens were -80% to -85%. Overall AEs were dose independent (elagolix alone, 70.0%-81.3%) but lower with placebo (56.0%) and add-back regimens (55.6%-70.6%). Hot flush was the most common AE (elagolix alone, 45.5%-62.5%; placebo, 12.0%; add-back regimens, 18.5%-26.5%). CONCLUSION(S): Elagolix significantly reduced heavy menstrual bleeding in women with fibroids. Low-dose add-back regimens substantially reduced flushing. CLINICAL TRIAL REGISTRATION NUMBER: NCT01441635.

Taste comparisons for lansoprazole strawberry-flavoured delayed-release orally disintegrating tablet and ranitidine peppermint-flavoured syrup in children.

OBJECTIVE: To compare the flavour and taste preferences of two acid-inhibitory therapies in children. SUBJECTS AND SETTING: 104 (52 male and 52 female) healthy children aged 6-11 years participated in this phase IV single-centre, taste-test study after parental consent was obtained. METHODS: Children were divided into two groups based upon age: group 1 included children aged 6-8 years and group 2 included children aged 9-11 years. Within each group an equal number of male and female subjects were recruited. Within each of the four strata defined by group and sex, an equal number of subjects were randomised to taste the strawberry-flavoured lansoprazole 15mg orally disintegrating tablet or the ranitidine 75mg/5mL peppermint-flavoured syrup samples in position 1. In group 1, the lansoprazole 15mg delayed-release orally disintegrating tablet was dispersed in 5mL of water, while in group 2, children gently rolled the tablet on the tongue until dissolution, before swallowing the particles. Children given the dose of lansoprazole dispersed in water (group 1) and the ranitidine dose (groups 1 and 2) were to taste it, swish it in their mouth for up to 10 seconds, and then swallow it. Children were given ambient temperature water and unsalted crackers to cleanse the palate during a 10-minute break between tastings. MAIN OUTCOME MEASURES: After each tasting, children rated their degree of liking on a five-point facial hedonic scale (5 = like very much, 1 = dislike very much). Product preference was recorded after the tasting of both samples. RESULTS: Among group 1 and group 2 participants, 86.5% (45/52) and 90.4% (47/52) of children, respectively, 'liked' ('like a little' or 'like very much') the strawberry-flavoured lansoprazole orally disintegrating tablet. The proportion of children who 'liked' the peppermint-flavoured ranitidine syrup was lower than the proportion who liked lansoprazole, and the proportions were similar between the groups: 13.5% (7/52) in group 1 and 9.6% (5/52) in group 2. Children in both groups preferred the strawberry-flavoured lansoprazole delayed-release orally disintegrating tablet: 92% (95% CI 81.1, 97.8; p < 0.001) of those in group 1 and 98% (95% CI 89.7, 100.0; p < 0.001) of those in group 2. CONCLUSION: After tasting both products, >92% of children aged from 6-11 years preferred the strawberry-flavoured lansoprazole delayed-release orally disintegrating tablet, either dissolved in a small amount of water or allowed to dissolve on the tongue, over the peppermint-flavoured ranitidine syrup.