Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain

NCT02143713 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: M12-8212013-001047-31
• Study Type: interventional
• Target: 496
• Locations: 0 countries
• Sites: N/A

Brief Summary

A randomized study evaluating the continued safety and efficacy of elagolix in the management of moderate to severe endometriosis associated pain in adult pre-menopausal women who completed 6 months treatment in pivotal Study M12-671 (NCT01931670).

Conditions

Endometriosis

Keywords

Endometriosis-associated pain; Elagolix; Gonadotropin-releasing Hormone Antagonist; Dysmenorrhea (DYS); Non-menstrual Pelvic Pain (NMPP); Dyspareunia

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment

  Response was defined as a reduction of -0.85 or more from baseline in dysmenorrhea (pain during menstruation) as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a \< 15% increase in average rescue analgesic pill count and no additional analgesic). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic use for endometriosis-associated pain daily and dysmenorrhea and its impact on daily activities each day of their period in an electronic diary (e-Diary). Dysmenorrhea was assessed according to the following: * 0: No discomfort * 1: Mild discomfort but I was easily able to do the things I usually do * 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3: Severe pain that made it difficult to do the things I usually do. Analgesic use and pain scores were averaged over the 35 days prior to each visit.

  Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6

• Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment

  Response was defined as a reduction of -0.43 or greater from baseline for non-menstrual pelvic pain as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a \< 15% increase in average pill count of rescue analgesics and no additional analgesics). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options: * 0: No discomfort * 1: Mild discomfort but I was easily able to do the things I usually do * 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do * 3: Severe pain that made it difficult to do the things I usually do. Pain scores and analgesic use were averaged over the 35 days prior to each visit.

  Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6

Secondary Outcomes (16)

• Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment

  Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5

• Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment

  Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5

• Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment

  Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

• Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment

  Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

• Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment

  Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6

Study Arms (2)

Elagolix 150 mg QD

EXPERIMENTAL

Participants received elagolix 150 mg tablets once a day (QD) for 6 months.

Drug: Elagolix

Elagolix 200 mg BID

EXPERIMENTAL

Participants received elagolix 200 mg tablets twice a day (BID) for 6 months.

Drug: Elagolix

Interventions

Elagolix DRUG

Elagolix tablets administered orally

Also known as: Orilissa™

Elagolix 150 mg QD; Elagolix 200 mg BID

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has completed the 6-Month Treatment Period in pivotal study M12-671.
• Agrees to use required birth control methods during the study through Month 6 of the Post-treatment Follow-up period

You may not qualify if:

• Clinically significant gynecological condition
• Bone mineral density (BMD) loss greater than or equal to 8 percent in the spine, femoral neck or total hip
• Plans to become pregnant in the next 18 months

Sponsors & Collaborators

• AbbVie: lead

Related Publications (6)

• Surrey E, Taylor HS, Giudice L, Lessey BA, Abrao MS, Archer DF, Diamond MP, Johnson NP, Watts NB, Gallagher JC, Simon JA, Carr BR, Dmowski WP, Leyland N, Singh SS, Rechberger T, Agarwal SK, Duan WR, Schwefel B, Thomas JW, Peloso PM, Ng J, Soliman AM, Chwalisz K. Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies. Obstet Gynecol. 2018 Jul;132(1):147-160. doi: 10.1097/AOG.0000000000002675.

  PMID: 29889764 BACKGROUND

• 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

• 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

• 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

• 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

• 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; Dyspareunia

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; Genital Diseases, Male; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

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: May 19, 2014
• First Posted: May 21, 2014
• Study Start: May 27, 2014
• Primary Completion: June 22, 2016
• Study Completion: May 23, 2017
• Last Updated: July 13, 2021
• Results First Posted: September 7, 2018

Record last verified: 2021-07