PMID- 28579415
OWN - NLM
STAT- MEDLINE
DCOM- 20170818
LR  - 20180208
IS  - 1556-5653 (Electronic)
IS  - 0015-0282 (Linking)
VI  - 108
IP  - 1
DP  - 2017 Jul
TI  - Elagolix for the management of heavy menstrual bleeding associated with uterine 
      fibroids: results from a phase 2a proof-of-concept study.
PG  - 152-160.e4
LID - S0015-0282(17)30362-X [pii]
LID - 10.1016/j.fertnstert.2017.05.006 [doi]
AB  - OBJECTIVE: To evaluate the safety and efficacy of elagolix vs. placebo and 
      elagolix with low-dose E(2)/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 E(2) 0.5 mg/norethindrone acetate 0.1 mg or elagolix 300 mg BID plus 
      E(2) 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.
CI  - Copyright (c) 2017 American Society for Reproductive Medicine. Published by 
      Elsevier Inc. All rights reserved.
FAU - Archer, David F
AU  - Archer DF
AD  - Eastern Virginia Medical School, Norfolk, Virginia. Electronic address: 
      archerdf@evms.edu.
FAU - Stewart, Elizabeth A
AU  - Stewart EA
AD  - Mayo Clinic and Mayo Medical School, Rochester, Minnesota.
FAU - Jain, Rita I
AU  - Jain RI
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Feldman, Robert A
AU  - Feldman RA
AD  - Miami Research Associates, Miami, Florida.
FAU - Lukes, Andrea S
AU  - Lukes AS
AD  - Carolina Women's Research and Wellness Center, Durham, North Carolina.
FAU - North, Janine D
AU  - North JD
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Soliman, Ahmed M
AU  - Soliman AM
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Gao, Jingjing
AU  - Gao J
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Ng, Juki W
AU  - Ng JW
AD  - AbbVie Inc, North Chicago, Illinois.
FAU - Chwalisz, Kristof
AU  - Chwalisz K
AD  - AbbVie Inc, North Chicago, Illinois.
LA  - eng
SI  - ClinicalTrials.gov/NCT01441635
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170601
PL  - United States
TA  - Fertil Steril
JT  - Fertility and sterility
JID - 0372772
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Pyrimidines)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 5B2546MB5Z (elagolix)
SB  - IM
MH  - Adult
MH  - Combined Modality Therapy/methods
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gonadotropin-Releasing Hormone/antagonists & inhibitors
MH  - Hormone Replacement Therapy/*methods
MH  - Humans
MH  - Hydrocarbons, Fluorinated/*administration & dosage/adverse effects
MH  - Leiomyoma/*complications/diagnosis/drug therapy
MH  - Menorrhagia/diagnosis/*drug therapy/*etiology
MH  - Pilot Projects
MH  - Pyrimidines/*administration & dosage/adverse effects
MH  - Treatment Outcome
MH  - Uterine Neoplasms/*complications/diagnosis/drug therapy
OTO - NOTNLM
OT  - Gonadotropin-releasing hormone antagonist
OT  - heavy menstrual bleeding
OT  - leiomyoma
OT  - nonpeptide
OT  - oral
EDAT- 2017/06/06 06:00
MHDA- 2017/08/19 06:00
CRDT- 2017/06/06 06:00
PHST- 2016/12/27 00:00 [received]
PHST- 2017/04/27 00:00 [revised]
PHST- 2017/05/03 00:00 [accepted]
PHST- 2017/06/06 06:00 [pubmed]
PHST- 2017/08/19 06:00 [medline]
PHST- 2017/06/06 06:00 [entrez]
AID - S0015-0282(17)30362-X [pii]
AID - 10.1016/j.fertnstert.2017.05.006 [doi]
PST - ppublish
SO  - Fertil Steril. 2017 Jul;108(1):152-160.e4. doi: 10.1016/j.fertnstert.2017.05.006. 
      Epub 2017 Jun 1.