Clinical trial NCT01760954: Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Adults With Moderate to Severe Endometriosis-Associated Pain
Official title: Extension Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis-Associated Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometriosis
Keywords: Endometriosis associated pain
Elagolix
Gonadotropin-Releasing Hormone Antagonist
Dysmenorrhea (DYS)
Non-Menstrual Pelvic Pain (NMPP)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2013-01-04
Enrollment: 506
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized study evaluating the continued safety and efficacy of elagolix in the management of moderate to severe endometriosis-associated pain in pre-menopausal women.

Detailed description: This is a Phase 3 multicenter, double blind randomized study to assess the continued safety and efficacy of the 150 mg once daily (QD) and 200 mg twice daily (BID) doses of elagolix in premenopausal women with moderate to severe endometriosis-associated pain who completed the 6 month treatment period in the pivotal study M12-665 (NCT01620528). The study consists of 2 periods: a 6 month Treatment Period and a post treatment follow-up period of up to 12 months.

Participants who received elagolix in the pivotal study who met all entry criteria continued to receive the same dose, either elagolix 150 mg QD or elagolix 200 mg BID for up to an additional 6 months in this extension study; participants who received placebo in the pivotal study were randomized in a 1:1 ratio to receive either elagolix 150 mg QD or elagolix 200 mg BID for up to 6 months.

An electronic diary will be used to collect endometriosis-associated pain, uterine bleeding, and analgesic medication use for endometriosis associated pain on a daily basis.

All participants who prematurely discontinued treatment (unless pregnant or elected surgery for endometriosis) or completed the 6-month Treatment Period in this extension study were to enter the Post-treatment Follow-up (PTFU) Period within this study for up to 12 months.

Eligibility criteria: Inclusion Criteria:

* Completed the 6 month Treatment Period in pivotal study M12-665 (NCT01620528)
* Agrees to use required birth control methods during the study through Month 6 of the Post-treatment Follow-up period

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and Month 6
measure: Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and Month 6
Secondary outcomes:
measure: Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5
measure: Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5
measure: Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Percent Change From Baseline in Dyspareunia Based on Daily Assessment
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Change From Baseline in Any Rescue Analgesic Use
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Change From Baseline in NSAID Rescue Analgesic Use
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Change From Baseline in Opioid Rescue Analgesic Use
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS)
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6
measure: Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved
timeFrame: Months 1, 2, 3, 4, 5, and 6
measure: Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 3, and 6
measure: Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and months 1, 3, and 6
measure: Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household
timeFrame: Baseline (defined as baseline of Study M12-665 for participants who received elagolix in the pivotal study and baseline of the extension study M12-667 for participants who received placebo in the pivotal study) and month 6
measure: Number of Participants With Non-study Health Visits During the Treatment Period
timeFrame: 6 months
measure: Number of Days in Hospital During the Treatment Period
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Surrey ES, Soliman AM, Agarwal SK, Snabes MC, Diamond MP. Impact of elagolix treatment on fatigue experienced by women with moderate to severe pain associated with endometriosis. Fertil Steril. 2019 Aug;112(2):298-304.e3. doi: 10.1016/j.fertnstert.2019.02.031. Epub 2019 Apr 13.
citation: 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.