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NCT02691494

Efficacy and Safety of Elagolix in Combination With Estradiol/Norethindrone Acetate for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women (Replicate Study)

Completed Phase 3 Results posted Last updated 13 July 2021
What this trial tests

Phase 3 trial testing Elagolix in Uterine Fibroids in 378 participants. Completed in 23 January 2019.

Timeline
3 February 2016
Primary endpoint
14 February 2018
23 January 2019

Quick facts

Lead sponsorAbbVie
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment378
Start date3 February 2016
Primary completion14 February 2018
Estimated completion23 January 2019
Sites105 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 51, female only, with Uterine Fibroids or Heavy Menstrual Bleeding. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Meeting the Criteria for Responder Primary · Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Percentage of responders, defined as participants who met the following conditions: * Menstrual blood loss (MBL) volume \< 80 mL during the Final Month (the last 28 days prior to and including the Reference Day, which is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date), and * ≥ 50% reduction in MBL volume from Baseline to the Final Month. Participants who prematurely discontinued study drug due to "lack of efficacy

GroupValue95% CI
Placebo10.5
Elagolix76.9
Elagolix + E2/NETA76.5
Change From Baseline in MBL Volume to the Final Month Secondary · Baseline and Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.

GroupValue95% CI
Placebo-4.3± 15.44
Elagolix-198.8± 15.44
Elagolix + E2/NETA-168.8± 10.72
Percentage of Participants With Suppression of Bleeding at the Final Month Secondary · Final Month (the last 28 days prior to and including the Reference Day), up to Month 6

Suppression of bleeding is defined as having 0 days of bleeding (spotting is allowed) during the Final Month with the interval starting from Study Day 11. The Reference Day is defined as the last visit date during the Treatment Period (last treatment visit date) or the last dose date if there are evaluable alkaline hematin data after the last treatment visit date and prior to or on the last dose date.

GroupValue95% CI
Placebo4.7
Elagolix88.9
Elagolix + E2/NETA61.0
Change From Baseline in MBL Volume to Month 6 Secondary · Month 0 (Baseline), Month 6

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

GroupValue95% CI
Placebo28.5± 16.68
Elagolix-223.7± 17.98
Elagolix + E2/NETA-198.1± 11.89
Change From Baseline in MBL Volume to Month 3 Secondary · Month 0 (Baseline), Month 3

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

GroupValue95% CI
Placebo-14.2± 11.57
Elagolix-211.1± 11.96
Elagolix + E2/NETA-200.3± 8.17
Percentage of Participants With Baseline Hemoglobin <= 10.5 g/dL Who Have an Increase in Hemoglobin > 2 g/dL at Month 6 Secondary · Month 0 (Baseline), Month 6
GroupValue95% CI
Placebo20.8
Elagolix40.0
Elagolix + E2/NETA50.0
Change From Baseline in MBL Volume to Month 1 Secondary · Month 0 (Baseline), Month 1

Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period, in which the total MBL volume is from all validated and non-validated sanitary products and the MBL volume of validated sanitary products only (excluding non-validated sanitary products) was greater than 80 mL.

GroupValue95% CI
Placebo-2.1± 14.31
Elagolix-196.6± 14.74
Elagolix + E2/NETA-127.0± 10.14

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug through 6 months of treatment with a 30-day follow-up period for participants who did not enroll in the extension study (Study M12-816). Mean (SD) treatment exposure was 160.3 (51.75), 155.2 (65.19), and 158.7 (54.68) days for the Placebo, Elagolix, and Elagolix and E2-NETA arms, respectively. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 1/94 (1%)
Deaths: 0/94
Elagolix
Serious: 4/95 (4%)
Deaths: 0/95
Elagolix + E2-NETA
Serious: 7/189 (4%)
Deaths: 0/189

Serious adverse events (13 terms)

ReactionSystemPlaceboElagolixElagolix + E2-NETA
ANAEMIABlood and lymphatic system disorders
HYPERTHYROIDISMEndocrine disorders
SMALL INTESTINAL OBSTRUCTIONGastrointestinal disorders
CHOLELITHIASISHepatobiliary disorders
APPENDICITISInfections and infestations
CELLULITISInfections and infestations
OBESITYMetabolism and nutrition disorders
ABORTION COMPLETEPregnancy, puerperium and perinatal conditions
ANXIETYPsychiatric disorders
DYSFUNCTIONAL UTERINE BLEEDINGReproductive system and breast disorders
DYSMENORRHOEAReproductive system and breast disorders
MENORRHAGIAReproductive system and breast disorders
PELVIC PAINReproductive system and breast disorders
Other adverse events (11 terms — click to expand)

ReactionSystemPlaceboElagolixElagolix + E2-NETA
HOT FLUSHVascular disorders
NIGHT SWEATSSkin and subcutaneous tissue disorders
HEADACHENervous system disorders
NAUSEAGastrointestinal disorders
URINARY TRACT INFECTIONInfections and infestations
FATIGUEGeneral disorders
NASOPHARYNGITISInfections and infestations
LIBIDO DECREASEDPsychiatric disorders
ARTHRALGIAMusculoskeletal and connective tissue disorders
MOOD SWINGSPsychiatric disorders
DYSMENORRHOEAReproductive system and breast disorders

Most-reported serious reactions: ANAEMIA, HYPERTHYROIDISM, SMALL INTESTINAL OBSTRUCTION, CHOLELITHIASIS, APPENDICITIS, CELLULITIS, OBESITY, ABORTION COMPLETE.

Data from ClinicalTrials.gov NCT02691494 adverse events section.

Sponsor's own description

This study seeks to evaluate the efficacy, safety and tolerability of elagolix alone and in combination with estradiol/norethindrone acetate for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids.
    Schlaff WD, Ackerman RT, Al-Hendy A, Archer DF, et al · · 2020 · cited 125× · PMID 31971678 · DOI 10.1056/nejmoa1904351
  2. Elagolix: First Global Approval.
    Lamb YN. · · 2018 · cited 53× · PMID 30194661 · DOI 10.1007/s40265-018-0977-4
  3. Moving Toward Individualized Medicine for Uterine Leiomyomas.
    Laughlin-Tommaso SK, Stewart EA. · · 2018 · cited 25× · PMID 30130343 · DOI 10.1097/aog.0000000000002785
  4. Predictors of response for elagolix with add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids.
    Al-Hendy A, Bradley L, Owens CD, Wang H, et al · · 2021 · cited 24× · PMID 32702363 · DOI 10.1016/j.ajog.2020.07.032
  5. Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.
    Ali M, A R S, Al Hendy A. · · 2021 · cited 20× · PMID 33682578 · DOI 10.1080/17512433.2021.1900726
  6. Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis.
    Muneyyirci-Delale O, Archer DF, Owens CD, Barnhart KT, et al · · 2021 · cited 17× · PMID 34553161 · DOI 10.1016/j.xfre.2021.05.004
  7. Clinical Utility Of Elagolix As An Oral Treatment For Women With Uterine Fibroids: A Short Report On The Emerging Efficacy Data.
    Neri M, Melis GB, Giancane E, Vallerino V, et al · · 2019 · cited 9× · PMID 31695514 · DOI 10.2147/ijwh.s185023
  8. Interdisciplinary model-informed drug development for extending duration of elagolix treatment in patients with uterine fibroids.
    Beck D, Winzenborg I, Gao W, Mostafa NM, et al · · 2022 · cited 7× · PMID 35695781 · DOI 10.1111/bcp.15440

Verify or expand the search:

Other trials of Elagolix

Trials testing the same drug.

Other recruiting trials for Uterine Fibroids

Currently open trials in the same condition.

Other AbbVie trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing