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

David F. Archer, Elizabeth A Stewart, Rita I. Jain, Robert A. Feldman, Andrea S. Lukes, Janine D. North, Ahmed M. Soliman, Jingjing Gao, Juki W. Ng, Kristof Chwalisz

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)152-160.e4
JournalFertility and Sterility
Volume108
Issue number1
DOIs
StatePublished - Jul 1 2017

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Leiomyoma
Hemorrhage
Placebos
elagolix
Therapeutics
Progestins
Least-Squares Analysis
Cohort Studies
Outcome Assessment (Health Care)
Clinical Trials
Safety

Keywords

  • Gonadotropin-releasing hormone antagonist
  • heavy menstrual bleeding
  • leiomyoma
  • nonpeptide
  • oral

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids : results from a phase 2a proof-of-concept study. / Archer, David F.; Stewart, Elizabeth A; Jain, Rita I.; Feldman, Robert A.; Lukes, Andrea S.; North, Janine D.; Soliman, Ahmed M.; Gao, Jingjing; Ng, Juki W.; Chwalisz, Kristof.

In: Fertility and Sterility, Vol. 108, No. 1, 01.07.2017, p. 152-160.e4.

Research output: Contribution to journalArticle

Archer, David F. ; Stewart, Elizabeth A ; Jain, Rita I. ; Feldman, Robert A. ; Lukes, Andrea S. ; North, Janine D. ; Soliman, Ahmed M. ; Gao, Jingjing ; Ng, Juki W. ; Chwalisz, Kristof. / Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids : results from a phase 2a proof-of-concept study. In: Fertility and Sterility. 2017 ; Vol. 108, No. 1. pp. 152-160.e4.
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abstract = "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.",
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T2 - results from a phase 2a proof-of-concept study

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AU - Stewart, Elizabeth A

AU - Jain, Rita I.

AU - Feldman, Robert A.

AU - Lukes, Andrea S.

AU - North, Janine D.

AU - Soliman, Ahmed M.

AU - Gao, Jingjing

AU - Ng, Juki W.

AU - Chwalisz, Kristof

PY - 2017/7/1

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N2 - 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.

AB - 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.

KW - Gonadotropin-releasing hormone antagonist

KW - heavy menstrual bleeding

KW - leiomyoma

KW - nonpeptide

KW - oral

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