EndometriosisPhase 3ELARIS EM-IINCT01931670

A Global Phase 3 Study to Evaluate the Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis-Associated Pain

A Phase 3 study testing Elagolix in people with Endometriosis, run by AbbVie.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

A randomized study evaluating the safety and efficacy of elagolix in the management of moderate to severe endometriosis-associated pain in adult premenopausal female subjects. Read more about this study

Who is it for?: Ages 18 to 49 years, women only
Conditions the study is for: Endometriosis
What is being tested?: Elagolix
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 815 participants
Where: No sites listed yet
Study dates: 9 Sep 2013to 19 Dec 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 49 years
Women only
No healthy volunteers
Adult

Who may be able to join

Premenopausal female, between 18 and 49 years of age, inclusive, at the time of signing consent.
Clinical diagnosis of endometriosis (laparoscopy or laparotomy) performed within 10 years of entry into the Washout Period.
Agrees to use required birth control methods during the entire length of participation in the study.
Subject has a Composite Pelvic Signs and Symptoms Score total score of 6 or greater at Screening with a score of at least 2 for dysmenorrhea AND at least 2 for non-menstrual pelvic pain.
Subjects must have at least two regular menstrual cycles with an interval of 24-38 days within the Screening Period, prior to Day 1.

Who cannot join

Subject is pregnant or breast feeding or is planning a pregnancy within the next 24 months or is less than 6 months postpartum, post-abortion, or post-pregnancy at the time of entry into the Screening Period.
Subject has a history of previous non-response to gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, Depot medroxyprogesterone acetate, or aromatase inhibitors as assessed by subject report of no improvement in dysmenorrhea or non-menstrual pelvic pain.
Subject has chronic pelvic pain that is not caused by endometriosis that requires chronic analgesic or other chronic therapy, or that would interfere with the assessment of endometriosis related pain.
Clinically significant gynecologic condition identified on Screening transvaginal ultrasound or endometrial biopsy.
Subject has a history of osteoporosis or other metabolic bone disease.
Subject has a current history of undiagnosed abnormal uterine bleeding.

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis-Associated Pain

A randomized study evaluating the safety and efficacy of elagolix in the management of moderate to severe endometriosis-associated pain in adult premenopausal female subjects.

Read the detailed description

The study consists of 4 periods: 1) Washout Period (if applicable); 2) a Screening Period of up to 100 days prior to first dose; 3) a 6 month Treatment Period; and 4) a Post treatment Follow-up Period of up to 12 months (if applicable). An electronic diary will be dispensed and training provided to record endometriosis-associated pain, uterine bleeding, and analgesic medication use for endometriosis-associated pain on a daily basis. Pregnancy testing will be performed monthly throughout the study. Subjects will be required to use nonhormonal dual contraception during the study, and will be counseled on appropriate and effective forms of birth control to promote pregnancy prevention.

Conditions: Endometriosis
Being tested: placebo, Elagolix
Keywords: Non-Menstrual Pelvic Pain (NMPP), Dysmenorrhea (DYS), Elagolix, Endometriosis Associated Pain, Gonadotropin-Releasing Hormone Antagonist
Medical subject headings: Endometriosis, Dysmenorrhea

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

placeboOther
ElagolixDrug
Also called ABT-620, elagolix sodium

Study groups in NCT01931670
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo twice daily (BID) for the 6-month Treatment Period Receives: Other: placebo
Elagolix 150 mg QD	Experimental	Elagolix 150 mg once daily (QD) for the 6-month Treatment Period Receives: Drug: Elagolix
Elagolix 200 mg BID	Experimental	Elagolix 200 mg BID for the 6-month Treatment Period Receives: Drug: Elagolix

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS)
The DYS pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.85 or greater from Baseline in DYS pain as well as no increased rescue analgesic use for endometriosis-associated pain.
Measured: At Month 3 of the Treatment Period
Percentage of Responders at Month 3 Based on Daily Assessment of Non-Menstrual Pelvic Pain (NMPP)
The NMPP pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.43 or greater from Baseline in NMPP as well as no increased rescue analgesic use for endometriosis-associated pain.
Measured: At Month 3 of Treatment Period

Secondary outcomes (29)

Change From Baseline to Month 3 in Numeric Rating Scale (NRS) Scores
The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever).
Measured: Baseline, Month 3 of the Treatment Period
Change From Baseline to Month 6 in DYS
The DYS pain scale ranges from 0 (none) to 3 (severe).
Measured: Baseline, Month 6 of Treatment Period
Change From Baseline to Month 6 in NMPP
The NMPP pain scale ranges from 0 (none) to 3 (severe).
Measured: Baseline, Month 6 of Treatment Period
Change From Baseline to Month 3 in Analgesic Use Across Both Classes of Rescue Analgesics
Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts.
Measured: Baseline, Month 3 of Treatment Period
Change From Baseline to Month 6 in Analgesic Use Across Both Classes of Rescue Analgesics
Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts.
Measured: Baseline, Month 6 of Treatment Period
Change From Baseline to Month 3 in Dyspareunia (DYSP)
The DYSP pain scale ranges from 0 (absent) to 3 (severe).
Measured: Baseline, Month 3 of Treatment Period
Change From Baseline to Month 3 in Use of Narcotic Class of Medication (Opioids)
Permitted country-specific rescue narcotic analgesics included 5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen. Assessment was based on average pill counts.
Measured: Baseline, Month 3 of Treatment Period
Percentage of Responders for Each Month, Except Month 3, in DYS
The DYS pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.85 or greater from Baseline in DYS pain as well as no increased rescue analgesic use for endometriosis-associated pain.
Measured: Months 1, 2, 4, 5, 6 of the Treatment Period
Percentage of Responders for Each Month, Except Month 3, in NMPP
The NMPP pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.43 or greater from Baseline in NMPP as well as no increased rescue analgesic use for endometriosis-associated pain.
Measured: Months 1, 2, 4, 5, 6 of the Treatment Period
Percentage of Responders at Each Month for DYSP
The DYSP pain scale ranged from 0 (absent) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.29 or greater from Baseline in DYSP as well as no increased rescue analgesic use for endometriosis-associated pain.
Measured: Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for DYS
The DYS pain scale ranges from 0 (none) to 3 (severe).
Measured: Baseline (Prior to administering study drug), Months 1, 2, 3, 4, 5 of Treatment Period
Percent Change From Baseline to Each Month in Mean Pain Score for DYS
The DYS pain scale ranges from 0 (none) to 3 (severe).
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for NMPP
The NMPP pain scale ranges from 0 (none) to 3 (severe).
Measured: Baseline, Months 1, 2, 3, 4, 5 of Treatment Period
Percent Change From Baseline to Each Month in the Mean Pain Score for NMPP
The NMPP pain scale ranges from 0 (none) to 3 (severe).
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 3, in the Mean Pain Score of DYSP
The DYSP pain scale ranged from 0 (absent) to 3 (severe).
Measured: Baseline, Months 1, 2, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Months 3 and 6, in Analgesic Use Across Both Classes of Rescue Analgesics
Permitted rescue medications included the nonsteroidal anti-inflammatory drug naproxen (500 or 550 mg), and one country-specific narcotic analgesic (5 mg hydrocodone + 300 or 325 mg acetaminophen, or 30 mg codeine + 500 mg acetaminophen, or 30 mg codeine, or 37.5 mg tramadol + 325 mg acetaminophen). Assessment was based on average pill counts.
Measured: Baseline, Months 1, 2, 4, 5
Patient Global Impression of Change (PGIC) Questionnaire
The PGIC questionnaire is a self-reported 7-point scale rating a participant's overall impression of change from 1 = very much improved to 7 = very much worse. Participants evaluated the change in their endometriosis-associated pain since initiation of study drug.
Measured: Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 3, in NRS Scores
The NRS for overall endometriosis-associated pain ranges 0 (none) to 10 (worst pain ever).
Measured: Baseline, Months 1, 2, 4, 5, 6 of Treatment Period
Change From Baseline to Each Scheduled Assessment in the Pain Domain of Endometriosis Health Profile-30 (EHP-30) Questionnaire Scores
The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.
Measured: Baseline, Months 1, 3, 6 of Treatment Period
Change From Baseline to Each Scheduled Assessment in the Sexual Intercourse Domain of EHP-30 Questionnaire Scores
The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.
Measured: Baseline, Months 1, 3, 6 of Treatment Period
Change From Baseline to Each Month in Health Related Productivity Questionnaire (HRPQ): Number of Hours of Work Lost From Workplace Due to Absenteeism
The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism) in the 7 days prior to survey administration.
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism
The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism) in the 7 days prior to survey administration.
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism
The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to presenteeism [working while sick]) in the 7 days prior to survey administration.
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism
The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to presenteeism [working while sick]) in the 7 days prior to survey administration.
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace
The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the workplace due to absenteeism and presenteeism) in the 7 days prior to survey administration.
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household
The HRPQ consists of questions measuring the impact of endometriosis-associated pain and its treatment on work productivity (number of work hours lost from the household due to absenteeism and presenteeism) in the 7 days prior to survey administration.
Measured: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Number of Participants With Endometriosis-Related Non-Study Health Visits During the Treatment Period
This is assessed using Health Resource Utilization Questionnaire (HRUQ).
Measured: Months 1, 2, 3, 4, 5, 6 of Treatment Period
Number of Days of Hospitalization
This is assessed using HRUQ.
Measured: Up to Month 6 of Treatment Period
Number of Participants With Emergency Room/Outpatient Procedures During the Treatment Period, by Type
This is assessed using HRUQ.
Measured: Up to Month 6 of Treatment Period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Sep 201319 Dec 2016

First posted29 Aug 2013 (estimated)
Study start9 Sep 2013
Primary completion6 Jan 2016
Study completion19 Dec 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (15)Papers the sponsor has linked to this study.
Other trials for EndometriosisStudies of the same condition, open and under way.
More trials run by AbbVieThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 815 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01931670
Sponsor's protocol ID: M12-671
Other IDs: 2011-004295-11
Acronym: ELARIS EM-II
Status last verified: Mar 2018
First submitted: 27 Aug 2013
Last updated: 7 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med. 2017 Jul 6;377(1):28-40. doi: 10.1056/NEJMoa1700089. Epub 2017 May 19.
PubMed 28525302
Beck D, Winzenborg I, Liu M, Degner J, Mostafa NM, Noertersheuser P, Shebley M. Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. Clin Pharmacokinet. 2022 Apr;61(4):577-587. doi: 10.1007/s40262-021-01096-w. Epub 2021 Dec 8.
PubMed 34878624
Abrao MS, Surrey E, Gordon K, Snabes MC, Wang H, Ijacu H, Taylor HS. Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients. BMC Womens Health. 2021 Jun 16;21(1):246. doi: 10.1186/s12905-021-01385-3.
PubMed 34134684
Stodtmann S, Nader A, Polepally AR, Suleiman AA, Winzenborg I, Noertersheuser P, Ng J, Mostafa NM, Shebley M. Validation of a quantitative systems pharmacology model of calcium homeostasis using elagolix Phase 3 clinical trial data in women with endometriosis. Clin Transl Sci. 2021 Jul;14(4):1611-1619. doi: 10.1111/cts.13040. Epub 2021 May 7.
PubMed 33963686
Beck D, Winzenborg I, Gao W, Mostafa NM, Noertersheuser P, Chiuve SE, Owens C, Shebley M. Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women. Clin Transl Sci. 2021 Jul;14(4):1452-1463. doi: 10.1111/cts.13006. Epub 2021 Apr 8.
PubMed 33650259
Agarwal SK, Singh SS, Archer DF, Mai Y, Chwalisz K, Gordon K, Surrey E. Endometriosis-Related Pain Reduction During Bleeding and Nonbleeding Days in Women Treated with Elagolix. J Pain Res. 2021 Feb 2;14:263-271. doi: 10.2147/JPR.S284703. eCollection 2021.
PubMed 33564263
Pokrzywinski RM, Soliman AM, Snabes MC, Chen J, Taylor HS, Coyne KS. Responsiveness and thresholds for clinically meaningful changes in worst pain numerical rating scale for dysmenorrhea and nonmenstrual pelvic pain in women with moderate to severe endometriosis. Fertil Steril. 2021 Feb;115(2):423-430. doi: 10.1016/j.fertnstert.2020.07.013. Epub 2020 Oct 14.
PubMed 33066973
Abbas Suleiman A, Nader A, Winzenborg I, Beck D, Polepally AR, Ng J, Noertersheuser P, Mostafa NM. Exposure-Safety Analyses Identify Predictors of Change in Bone Mineral Density and Support Elagolix Labeling for Endometriosis-Associated Pain. CPT Pharmacometrics Syst Pharmacol. 2020 Nov;9(11):639-648. doi: 10.1002/psp4.12560. Epub 2020 Oct 8.
PubMed 32945631
Taylor HS, Soliman AM, Johns B, Pokrzywinski RM, Snabes M, Coyne KS. Health-Related Quality of Life Improvements in Patients With Endometriosis Treated With Elagolix. Obstet Gynecol. 2020 Sep;136(3):501-509. doi: 10.1097/AOG.0000000000003917.
PubMed 32769633
Winzenborg I, Polepally AR, Nader A, Mostafa NM, Noertersheuser P, Ng J. Effect of Elagolix Exposure on Clinical Efficacy End Points in Phase III Trials in Women With Endometriosis-Associated Pain: An Application of Markov Model. CPT Pharmacometrics Syst Pharmacol. 2020 Aug;9(8):466-475. doi: 10.1002/psp4.12545. Epub 2020 Jul 31.
PubMed 32621325
Surrey ES, Soliman AM, Palac HL, Agarwal SK. Impact of Elagolix on Workplace and Household Productivity Among Women with Moderate to Severe Pain Associated with Endometriosis: A Pooled Analysis of Two Phase III Trials. Patient. 2019 Dec;12(6):651-660. doi: 10.1007/s40271-019-00394-7.
PubMed 31654294
Pokrzywinski RM, Soliman AM, Chen J, Snabes M, Diamond MP, Surrey E, Coyne KS. Impact of elagolix on work loss due to endometriosis-associated pain: estimates based on the results of two phase III clinical trials. Fertil Steril. 2019 Sep;112(3):545-551. doi: 10.1016/j.fertnstert.2019.04.031. Epub 2019 Jun 18.
PubMed 31227284
Rolla E. Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment. F1000Res. 2019 Apr 23;8:F1000 Faculty Rev-529. doi: 10.12688/f1000research.14817.1. eCollection 2019.
PubMed 31069056
Wang ST, Johnson SJ, Mitchell D, Soliman AM, Vora JB, Agarwal SK. Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA. J Comp Eff Res. 2019 Apr;8(5):337-355. doi: 10.2217/cer-2018-0124. Epub 2019 Feb 6.
PubMed 30724096
Winzenborg I, Nader A, Polepally AR, Liu M, Degner J, Klein CE, Mostafa NM, Noertersheuser P, Ng J. Population Pharmacokinetics of Elagolix in Healthy Women and Women with Endometriosis. Clin Pharmacokinet. 2018 Oct;57(10):1295-1306. doi: 10.1007/s40262-018-0629-6.
PubMed 29476499

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Endometriosis, Quality of Life
RecruitingPhase 1
Phase Ia Trial of HHK001 Compared With Enantone in Patients With Endometriosis
Endometriosis
Active, not recruiting
Feasibility of a Mindfulness Intervention for Endometriosis Surgery
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All Endometriosis trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis-Associated Pain
ClinicalTrials.gov ID: NCT01931670
Acronym / sponsor ID: ELARIS EM-II / M12-671
Conditions: Endometriosis
Keywords: Non-Menstrual Pelvic Pain (NMPP), Dysmenorrhea (DYS), Elagolix, Endometriosis Associated Pain, Gonadotropin-Releasing Hormone Antagonist
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 815 participants (actual)
Lead sponsor: AbbVieIndustry (pharma, biotech, devices)
Study start: 9 Sep 2013 (actual)
Primary completion: 6 Jan 2016 (actual)
Study completion: 19 Dec 2016 (actual)
First posted: 29 Aug 2013 (estimated)
Results: Posted 7 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

A randomized study evaluating the safety and efficacy of elagolix in the management of moderate to severe endometriosis-associated pain in adult premenopausal female subjects.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Placebo	Placebo comparator	Other: placeboPlacebo twice daily (BID) for the 6-month Treatment Period
Elagolix 150 mg QD	Experimental	Drug: ElagolixElagolix 150 mg once daily (QD) for the 6-month Treatment Period
Elagolix 200 mg BID	Experimental	Drug: ElagolixElagolix 200 mg BID for the 6-month Treatment Period

Who may qualify

Ages: 18 to 49 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (5 listed)

Premenopausal female, between 18 and 49 years of age, inclusive, at the time of signing consent.
Clinical diagnosis of endometriosis (laparoscopy or laparotomy) performed within 10 years of entry into the Washout Period.
Agrees to use required birth control methods during the entire length of participation in the study.
Subject has a Composite Pelvic Signs and Symptoms Score total score of 6 or greater at Screening with a score of at least 2 for dysmenorrhea AND at least 2 for non-menstrual pelvic pain.
Subjects must have at least two regular menstrual cycles with an interval of 24-38 days within the Screening Period, prior to Day 1.

Key exclusion criteria (6 listed)

Subject is pregnant or breast feeding or is planning a pregnancy within the next 24 months or is less than 6 months postpartum, post-abortion, or post-pregnancy at the time of entry into the Screening Period.
Subject has a history of previous non-response to gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, Depot medroxyprogesterone acetate, or aromatase inhibitors as assessed by subject report of no improvement in dysmenorrhea or non-menstrual pelvic pain.
Subject has chronic pelvic pain that is not caused by endometriosis that requires chronic analgesic or other chronic therapy, or that would interfere with the assessment of endometriosis related pain.
Clinically significant gynecologic condition identified on Screening transvaginal ultrasound or endometrial biopsy.
Subject has a history of osteoporosis or other metabolic bone disease.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
placebo	Other	Placebo
ElagolixAlso: ABT-620, elagolix sodium	Drug	Elagolix 150 mg QD, Elagolix 200 mg BID

Primary outcome

Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS)
Time frame: At Month 3 of the Treatment Period
The DYS pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.85 or greater from Baseline in DYS pain as well as no increased rescue analgesic use for endometriosis-associated pain.
Percentage of Responders at Month 3 Based on Daily Assessment of Non-Menstrual Pelvic Pain (NMPP)
Time frame: At Month 3 of Treatment Period
The NMPP pain scale ranges from 0 (none) to 3 (severe) as recorded in a daily electronic diary. The criteria for defining a participant as a responder included a reduction of -0.43 or greater from Baseline in NMPP as well as no increased rescue analgesic use for endometriosis-associated pain.

29 secondary outcomes

Change From Baseline to Month 3 in Numeric Rating Scale (NRS) Scores
Time frame: Baseline, Month 3 of the Treatment Period
Change From Baseline to Month 6 in DYS
Time frame: Baseline, Month 6 of Treatment Period
Change From Baseline to Month 6 in NMPP
Time frame: Baseline, Month 6 of Treatment Period
Change From Baseline to Month 3 in Analgesic Use Across Both Classes of Rescue Analgesics
Time frame: Baseline, Month 3 of Treatment Period
Change From Baseline to Month 6 in Analgesic Use Across Both Classes of Rescue Analgesics
Time frame: Baseline, Month 6 of Treatment Period
Change From Baseline to Month 3 in Dyspareunia (DYSP)
Time frame: Baseline, Month 3 of Treatment Period
Change From Baseline to Month 3 in Use of Narcotic Class of Medication (Opioids)
Time frame: Baseline, Month 3 of Treatment Period
Percentage of Responders for Each Month, Except Month 3, in DYS
Time frame: Months 1, 2, 4, 5, 6 of the Treatment Period
Percentage of Responders for Each Month, Except Month 3, in NMPP
Time frame: Months 1, 2, 4, 5, 6 of the Treatment Period
Percentage of Responders at Each Month for DYSP
Time frame: Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for DYS
Time frame: Baseline (Prior to administering study drug), Months 1, 2, 3, 4, 5 of Treatment Period
Percent Change From Baseline to Each Month in Mean Pain Score for DYS
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 6, in Mean Pain Score for NMPP
Time frame: Baseline, Months 1, 2, 3, 4, 5 of Treatment Period
Percent Change From Baseline to Each Month in the Mean Pain Score for NMPP
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 3, in the Mean Pain Score of DYSP
Time frame: Baseline, Months 1, 2, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Months 3 and 6, in Analgesic Use Across Both Classes of Rescue Analgesics
Time frame: Baseline, Months 1, 2, 4, 5
Patient Global Impression of Change (PGIC) Questionnaire
Time frame: Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month, Except Month 3, in NRS Scores
Time frame: Baseline, Months 1, 2, 4, 5, 6 of Treatment Period
Change From Baseline to Each Scheduled Assessment in the Pain Domain of Endometriosis Health Profile-30 (EHP-30) Questionnaire Scores
Time frame: Baseline, Months 1, 3, 6 of Treatment Period
Change From Baseline to Each Scheduled Assessment in the Sexual Intercourse Domain of EHP-30 Questionnaire Scores
Time frame: Baseline, Months 1, 3, 6 of Treatment Period
Change From Baseline to Each Month in Health Related Productivity Questionnaire (HRPQ): Number of Hours of Work Lost From Workplace Due to Absenteeism
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Absenteeism
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Workplace Due to Presenteeism
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Number of Hours of Work Lost From Household Due to Presenteeism
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Workplace
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Change From Baseline to Each Month in HRPQ: Total (Absenteeism and Presenteeism) Number of Hours of Work Lost From Household
Time frame: Baseline, Months 1, 2, 3, 4, 5, 6 of Treatment Period
Number of Participants With Endometriosis-Related Non-Study Health Visits During the Treatment Period
Time frame: Months 1, 2, 3, 4, 5, 6 of Treatment Period
Number of Days of Hospitalization
Time frame: Up to Month 6 of Treatment Period
Number of Participants With Emergency Room/Outpatient Procedures During the Treatment Period, by Type
Time frame: Up to Month 6 of Treatment Period

Results and safety

Results posted to the registry on 7 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	360	270
Elagolix 150 mg QD	226	178
Elagolix 200 mg BID	229	184

Primary outcome: Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS)

Time frame: At Month 3 of the Treatment Period. Number. Unit: percentage of participants

Measure	Placebo n = 353	Elagolix 150 mg QD n = 221	Elagolix 200 mg BID n = 225
Value	22.7	43.4	72.4

Placebo vs Elagolix 150 mg QD: p < 0.001, Regression, Logistic
Placebo vs Elagolix 200 mg BID: p < 0.001, Regression, Logistic

Population analysed: The modified intent-to-treat (mITT) analysis set; all randomized participants who took at least 1 dose of randomized, double-blind study drug. Population included mITT participants who either had data during the Month 3 35-day window or who prematurely discontinued prior to or at Month 3 and met the rules for last observation carried forward.

Primary outcome: Percentage of Responders at Month 3 Based on Daily Assessment of Non-Menstrual Pelvic Pain (NMPP)

Time frame: At Month 3 of Treatment Period. Number. Unit: percentage of participants

Measure	Placebo n = 353	Elagolix 150 mg QD n = 221	Elagolix 200 mg BID n = 225
Value	36.5	49.8	57.8

Placebo vs Elagolix 150 mg QD: p = 0.003, Regression, Logistic
Placebo vs Elagolix 200 mg BID: p < 0.001, Regression, Logistic

Population analysed: The mITT analysis set; all randomized participants who took at least 1 dose of randomized, double-blind study drug. Population included mITT participants who either had data during the Month 3 35-day window or who prematurely discontinued prior to or at Month 3 and met the rules for last observation carried forward.

29 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study treatment through 6 months of treatment plus up to 12 months of follow-up.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	12 of 360 (3.3%)	158 of 360 (43.9%)	0 of 360
Elagolix 150 mg QD	12 of 226 (5.3%)	128 of 226 (56.6%)	1 of 226
Elagolix 200 mg BID	5 of 229 (2.2%)	162 of 229 (70.7%)	0 of 229

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28525302Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, Diamond MP, Surrey E, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Rowan JP, Duan WR, Ng J, Schwefel B, Thomas JW, Jain RI, Chwalisz K. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med. 2017 Jul 6;377(1):28-40. doi: 10.1056/NEJMoa1700089. Epub 2017 May 19.
Derived from this study: PubMed 34878624Beck D, Winzenborg I, Liu M, Degner J, Mostafa NM, Noertersheuser P, Shebley M. Population Pharmacokinetics of Elagolix in Combination with Low-Dose Estradiol/Norethindrone Acetate in Women with Uterine Fibroids. Clin Pharmacokinet. 2022 Apr;61(4):577-587. doi: 10.1007/s40262-021-01096-w. Epub 2021 Dec 8.
Derived from this study: PubMed 34134684Abrao MS, Surrey E, Gordon K, Snabes MC, Wang H, Ijacu H, Taylor HS. Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients. BMC Womens Health. 2021 Jun 16;21(1):246. doi: 10.1186/s12905-021-01385-3.
Derived from this study: PubMed 33963686Stodtmann S, Nader A, Polepally AR, Suleiman AA, Winzenborg I, Noertersheuser P, Ng J, Mostafa NM, Shebley M. Validation of a quantitative systems pharmacology model of calcium homeostasis using elagolix Phase 3 clinical trial data in women with endometriosis. Clin Transl Sci. 2021 Jul;14(4):1611-1619. doi: 10.1111/cts.13040. Epub 2021 May 7.
Derived from this study: PubMed 33650259Beck D, Winzenborg I, Gao W, Mostafa NM, Noertersheuser P, Chiuve SE, Owens C, Shebley M. Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women. Clin Transl Sci. 2021 Jul;14(4):1452-1463. doi: 10.1111/cts.13006. Epub 2021 Apr 8.
Derived from this study: PubMed 33564263Agarwal SK, Singh SS, Archer DF, Mai Y, Chwalisz K, Gordon K, Surrey E. Endometriosis-Related Pain Reduction During Bleeding and Nonbleeding Days in Women Treated with Elagolix. J Pain Res. 2021 Feb 2;14:263-271. doi: 10.2147/JPR.S284703. eCollection 2021.
Derived from this study: PubMed 33066973Pokrzywinski RM, Soliman AM, Snabes MC, Chen J, Taylor HS, Coyne KS. Responsiveness and thresholds for clinically meaningful changes in worst pain numerical rating scale for dysmenorrhea and nonmenstrual pelvic pain in women with moderate to severe endometriosis. Fertil Steril. 2021 Feb;115(2):423-430. doi: 10.1016/j.fertnstert.2020.07.013. Epub 2020 Oct 14.
Derived from this study: PubMed 32945631Abbas Suleiman A, Nader A, Winzenborg I, Beck D, Polepally AR, Ng J, Noertersheuser P, Mostafa NM. Exposure-Safety Analyses Identify Predictors of Change in Bone Mineral Density and Support Elagolix Labeling for Endometriosis-Associated Pain. CPT Pharmacometrics Syst Pharmacol. 2020 Nov;9(11):639-648. doi: 10.1002/psp4.12560. Epub 2020 Oct 8.
Derived from this study: PubMed 32769633Taylor HS, Soliman AM, Johns B, Pokrzywinski RM, Snabes M, Coyne KS. Health-Related Quality of Life Improvements in Patients With Endometriosis Treated With Elagolix. Obstet Gynecol. 2020 Sep;136(3):501-509. doi: 10.1097/AOG.0000000000003917.
Derived from this study: PubMed 32621325Winzenborg I, Polepally AR, Nader A, Mostafa NM, Noertersheuser P, Ng J. Effect of Elagolix Exposure on Clinical Efficacy End Points in Phase III Trials in Women With Endometriosis-Associated Pain: An Application of Markov Model. CPT Pharmacometrics Syst Pharmacol. 2020 Aug;9(8):466-475. doi: 10.1002/psp4.12545. Epub 2020 Jul 31.
Derived from this study: PubMed 31654294Surrey ES, Soliman AM, Palac HL, Agarwal SK. Impact of Elagolix on Workplace and Household Productivity Among Women with Moderate to Severe Pain Associated with Endometriosis: A Pooled Analysis of Two Phase III Trials. Patient. 2019 Dec;12(6):651-660. doi: 10.1007/s40271-019-00394-7.
Derived from this study: PubMed 31227284Pokrzywinski RM, Soliman AM, Chen J, Snabes M, Diamond MP, Surrey E, Coyne KS. Impact of elagolix on work loss due to endometriosis-associated pain: estimates based on the results of two phase III clinical trials. Fertil Steril. 2019 Sep;112(3):545-551. doi: 10.1016/j.fertnstert.2019.04.031. Epub 2019 Jun 18.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

AbbVie Inc. study director

AbbVie

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Elagolix in people with Endometriosis, run by AbbVie.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Responders at Month 3 Based on Daily Assessment of Dysmenorrhea (DYS) (time frame: At Month 3 of the Treatment Period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01931670, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2018.