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

NCT01931670 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: M12-6712011-004295-11
• Study Type: interventional
• Target: 815
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Endometriosis

Keywords

Non-Menstrual Pelvic Pain (NMPP); Dysmenorrhea (DYS); Elagolix; Endometriosis Associated Pain; Gonadotropin-Releasing Hormone Antagonist

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  At Month 3 of Treatment Period

Secondary Outcomes (29)

• Change From Baseline to Month 3 in Numeric Rating Scale (NRS) Scores

  Baseline, Month 3 of the Treatment Period

• Change From Baseline to Month 6 in DYS

  Baseline, Month 6 of Treatment Period

• Change From Baseline to Month 6 in NMPP

  Baseline, Month 6 of Treatment Period

• Change From Baseline to Month 3 in Analgesic Use Across Both Classes of Rescue Analgesics

  Baseline, Month 3 of Treatment Period

• Change From Baseline to Month 6 in Analgesic Use Across Both Classes of Rescue Analgesics

  Baseline, Month 6 of Treatment Period

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo twice daily (BID) for the 6-month Treatment Period

Other: placebo

Elagolix 150 mg QD

EXPERIMENTAL

Elagolix 150 mg once daily (QD) for the 6-month Treatment Period

Drug: Elagolix

Elagolix 200 mg BID

EXPERIMENTAL

Elagolix 200 mg BID for the 6-month Treatment Period

Drug: Elagolix

Interventions

placebo OTHER

Placebo

Elagolix DRUG

Also known as: ABT-620, elagolix sodium

Elagolix 150 mg QD; Elagolix 200 mg BID

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Related Publications (15)

• 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.

  PMID: 28525302 RESULT

• 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.

  PMID: 34878624 DERIVED

• 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.

  PMID: 34134684 DERIVED

• 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.

  PMID: 33963686 DERIVED

• 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.

  PMID: 33650259 DERIVED

• 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.

  PMID: 33564263 DERIVED

• 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.

  PMID: 33066973 DERIVED

• 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.

  PMID: 32945631 DERIVED

• 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.

  PMID: 32769633 DERIVED

• 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.

  PMID: 32621325 DERIVED

• 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.

  PMID: 31654294 DERIVED

• 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.

  PMID: 31227284 DERIVED

• 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.

  PMID: 31069056 DERIVED

• 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.

  PMID: 30724096 DERIVED

• 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.

  PMID: 29476499 DERIVED

MeSH Terms

Conditions

Endometriosis; Dysmenorrhea

Interventions

elagolix

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pelvic Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: August 29, 2013
• Study Start: September 9, 2013
• Primary Completion: January 6, 2016
• Study Completion: December 19, 2016
• Last Updated: September 7, 2018
• Results First Posted: September 7, 2018

Record last verified: 2018-03