An Extension Study to Evaluate the Efficacy and Safety of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02925494
• Collaborator: (none)
• Enrollment: 433
• Locations: 124
• Arms: 2
• Actual Duration (Months): 30.2
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an extension study for women who have already received six months of treatment in the phase III clinical trial M12-815 (NCT02654054) or M12-817 (NCT02691494), and will evaluate the long-term efficacy and safety of elagolix administered alone and in combination with estradiol/norethindrone acetate for an additional six months in the treatment of heavy menstrual bleeding associated with uterine fibroids.

Condition or Disease	Intervention/Treatment	Phase
Uterine Fibroids; Heavy Menstrual Bleeding	Drug: Estradiol/Norethindrone Acetate; Drug: Elagolix	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 433 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Extension Study to Evaluate the Efficacy and Safety of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
• Actual Study Start Date: Sep 14, 2016
• Actual Primary Completion Date: May 7, 2018
• Actual Study Completion Date: Mar 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elagolix plus Estradiol/Norethindrone Acetate (E2/NETA) Elagolix 300 mg twice daily (BID) and E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) once daily (QD)	Drug: Estradiol/Norethindrone Acetate; capsules; Drug: Elagolix; film-coated tablets; Other Names: ABT-620 elagolix sodium
Experimental: Elagolix Elagolix 300 mg BID and placebo for E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD	Drug: Elagolix; film-coated tablets; Other Names: ABT-620 elagolix sodium

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Meeting the Criteria for Responder [From Month 0 (Baseline in Pivotal Study) to Final Month of Treatment Period (up through Month 6 in Extension Study)]

   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 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," "requires surgery or invasive intervention for treatment of uterine fibroids," or "adverse events" were considered non-responders regardless of whether she meets the two aforementioned responder criteria or not.

Secondary Outcome Measures

1. Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period [Month 0 (Baseline in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6)]

   Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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.

2. Percent Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period [Month 0 (Baseline in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6)]

   Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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.

3. Percentage of Participants With Suppression of Bleeding at the Final Month [Final Month of Treatment Period (up through 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.

4. Percentage of Participants With Baseline Hemoglobin Concentration ≤ 10.5 g/dL and an Increase From Baseline > 2 g/dL at Month 6 During the Treatment Period [Month 6]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 51 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant has completed the 6-Month Treatment Period of their respective Pivotal Study (either Study M12-815 or Study M12-817).

• Participant did not meet removal criteria in bone mineral density (BMD) decrease in the spine, total hip and femoral neck at Month 6 of the Treatment Period of their respective Pivotal Study

• Participant has negative urine and/or serum pregnancy test(s) results were consistently negative during the Treatment Period of their respective Pivotal Study and prior to first dose in this study.

• Participant's endometrial biopsy from the Month 6 Visit of their respective Pivotal Study shows no clinically significant endometrial pathology.

Exclusion Criteria:

• Participant met criteria for removal from therapy in her respective Pivotal Study.

• Participant is planning a pregnancy within the next 18 months.

• Participant has current suicidal markers as noted at the Month 6 visit of her respective pivotal study.

• Participant has any new medical conditions that may be unsuitable for participation.

• Participant is using any systemic corticosteroids for over 14 days or is likely to require treatment with systemic corticosteroids during the course of the study. Over-the-counter and prescription topical, inhaled, intranasal or injectable (for occasional use) corticosteroids are allowed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Clinical Therapeutics, LLC /ID# 153217	Birmingham	Alabama	United States	35235-3430
2	Alabama Clinical Therapeutics, LLC /ID# 153336	Birmingham	Alabama	United States	35235-3430
3	Choice Research, LLC /ID# 153492	Dothan	Alabama	United States	36303
4	Brown, Pearson, Guepet Gynecology /ID# 153278	Fairhope	Alabama	United States	36532
5	University of South Alabama /ID# 153415	Mobile	Alabama	United States	36604-3302
6	Mobile, Ob-Gyn, P.C. /ID# 153442	Mobile	Alabama	United States	36608
7	Mesa Obstetricians and Gynecol /ID# 153269	Mesa	Arizona	United States	85209
8	Core Healthcare Group /ID# 153282	Cerritos	California	United States	90703
9	Diagnamics Inc. /ID# 153347	Encinitas	California	United States	92024
10	Grossmont Ctr Clin Research /ID# 153324	La Mesa	California	United States	91942
11	Futura Research, Inc. /ID# 153345	Norwalk	California	United States	90650
12	Farid Yasharpour MD Medical Co /ID# 153482	San Fernando	California	United States	91340
13	Advanced Women's Health Institution /ID# 153401	Greenwood Village	Colorado	United States	80111
14	Medstar Health Research Institute /ID# 153321	Washington	District of Columbia	United States	20010
15	Emerson Clinical Research Inst /ID# 162755	Washington	District of Columbia	United States	20011
16	James A. Simon, MD, PC /ID# 153323	Washington	District of Columbia	United States	20036
17	Helix Biomedics, LLC /ID# 153440	Boynton Beach	Florida	United States	33436-6634
18	Brandon Premier Health Care, PA /ID# 165791	Brandon	Florida	United States	33510-3107
19	Florida Fertility Institute /ID# 153308	Clearwater	Florida	United States	33759
20	Omega Research Consultants, LLC /ID# 153381	DeBary	Florida	United States	32713-2260
21	KO Clinical Research, LLC /ID# 153198	Fort Lauderdale	Florida	United States	33316
22	Clinical Physiology Assoc. /ID# 153444	Fort Myers	Florida	United States	33916
23	Solutions Through Adv Rch /ID# 153283	Jacksonville	Florida	United States	32256
24	Meridien Research /ID# 153310	Kenneth City	Florida	United States	33709-3113
25	Altus Research, Inc /ID# 153307	Lake Worth	Florida	United States	33461
26	South Florida Wellness & Clinic /ID# 153420	Margate	Florida	United States	33063
27	Precision Research Org, LLC /ID# 153276	Miami Lakes	Florida	United States	33016-1501
28	LCC Medical Research Institute /ID# 153296	Miami	Florida	United States	33126
29	Invictus Clinical Research Group,LLC /ID# 153196	Miami	Florida	United States	33144
30	Healthcare Clinical Data, Inc /ID# 153425	Miami	Florida	United States	33161
31	Ocean Blue Med Research Ctr /ID# 153225	Miami	Florida	United States	33166
32	Suncoast Clinical Research /ID# 153206	New Port Richey	Florida	United States	34652
33	Advanced Research Institute /ID# 153413	New Port Richey	Florida	United States	34653
34	Clinical Associates of Orlando /ID# 153427	Orlando	Florida	United States	32806
35	Unified Womens Clin Research /ID# 153229	Panama City	Florida	United States	32045
36	All Wmns HC of West Broward /ID# 153434	Plantation	Florida	United States	33324
37	Oncova Clinical Research, Inc. /ID# 153497	Saint Cloud	Florida	United States	34769
38	Physician Care Clin. Res., LLC /ID# 153210	Sarasota	Florida	United States	34239
39	Qps-Mra, Llc /Id# 153456	South Miami	Florida	United States	33143
40	University of South Florida /ID# 153271	Tampa	Florida	United States	33612
41	Axcess Medical Research /ID# 153500	Wellington	Florida	United States	33414
42	Virtus Research Consultant,LLC /ID# 153398	Wellington	Florida	United States	33414
43	Comprehensive Clinical Trials /ID# 153350	West Palm Beach	Florida	United States	33409
44	Atlanta Medical Research Insti /ID# 153298	Alpharetta	Georgia	United States	30005-4419
45	Paramount Research Solutions /ID# 153424	Alpharetta	Georgia	United States	30005
46	Paramount Research Solutions /ID# 160974	Alpharetta	Georgia	United States	30005
47	Mount Vernon Clinical Res, LLC /ID# 153403	Atlanta	Georgia	United States	30328
48	Atlanta Women's Research Inst /ID# 153212	Atlanta	Georgia	United States	30342
49	Masters of Clinical Research, Inc. /ID# 153295	Augusta	Georgia	United States	30909
50	Paramount Research Solutions /ID# 153351	College Park	Georgia	United States	30349
51	Fellows Research Alliance, Inc /ID# 153227	Savannah	Georgia	United States	31406
52	Clinical Research Consultants of Atlanta /ID# 153285	Suwanee	Georgia	United States	30024-6988
53	Atlanta Gynecology Research Institute /ID# 200074	Suwanee	Georgia	United States	30024-7159
54	Sonora Clinical Research /ID# 153231	Meridian	Idaho	United States	83646-1144
55	Affinity Clinical Research /ID# 153417	Oak Brook	Illinois	United States	60523
56	Bluegrass Clinical Research /ID# 153280	Louisville	Kentucky	United States	40291
57	Clinical Trials Management, LLC - Covington /ID# 153211	Covington	Louisiana	United States	70433
58	Clinical Trials Management, LLC - Covington /ID# 153439	Covington	Louisiana	United States	70433
59	Ochsner Baptist Medical Center /ID# 153459	New Orleans	Louisiana	United States	70115
60	Omni Fertility and Laser Insti /ID# 153228	Shreveport	Louisiana	United States	71118
61	Baltimore Suburban Health /ID# 168386	Baltimore	Maryland	United States	21208
62	NECCR Fall River LLC /ID# 153274	Fall River	Massachusetts	United States	02720-2972
63	Genesis Clinical Research /ID# 153379	Fall River	Massachusetts	United States	02720
64	Great Lakes Research Group,Inc /ID# 153302	Bay City	Michigan	United States	48706
65	Saginaw Valley Med Res Group /ID# 153498	Saginaw	Michigan	United States	48604
66	Wayne State University Physician Group - Southfield /ID# 153418	Southfield	Michigan	United States	48034
67	Accent Clinical Trials /ID# 153474	Las Vegas	Nevada	United States	89106-4017
68	Office of Edmond E. Pack, MD /ID# 153411	Las Vegas	Nevada	United States	89113
69	Mabey, Las Vegas, NV /ID# 153314	Las Vegas	Nevada	United States	89128
70	Lawrence OB/GYN /ID# 153218	Lawrenceville	New Jersey	United States	08648
71	Jersey Shore University Medical Center /ID# 153495	Neptune	New Jersey	United States	07753-4859
72	Bosque Women's Care /ID# 153223	Albuquerque	New Mexico	United States	87109
73	SUNY Downstate Medical Center /ID# 153344	Brooklyn	New York	United States	11203
74	Manhattan Medical Research /ID# 153386	New York	New York	United States	10016-6023
75	Weill Cornell Medicine /ID# 153275	New York	New York	United States	10032-3725
76	Cwrwc /Id# 153313	Durham	North Carolina	United States	27713
77	Unified Women's Clinical Research-Greensboro /ID# 153499	Greensboro	North Carolina	United States	27408
78	Pinewest Ob-Gyn, Inc. /ID# 153197	High Point	North Carolina	United States	27262
79	Eastern Carolina Women's Centr /ID# 153341	New Bern	North Carolina	United States	28562
80	Unified Women's Clinical Resea /ID# 153312	Raleigh	North Carolina	United States	27607
81	Wake Research Associates, LLC /ID# 153402	Raleigh	North Carolina	United States	27612
82	Unified Women's Clinical Resea /ID# 153297	Winston-Salem	North Carolina	United States	27103
83	Clinical Inquest Center Ltd /ID# 153436	Beavercreek	Ohio	United States	45432
84	CTI Clinical Research Center /ID# 153201	Cincinnati	Ohio	United States	45212
85	University Hospitals Cleveland /ID# 153450	Cleveland	Ohio	United States	44106
86	University of Toledo /ID# 153409	Toledo	Ohio	United States	43614
87	Comprehensive Womens Care /ID# 153396	Westerville	Ohio	United States	43081
88	Legacy Medical Group-Portland /ID# 168286	Portland	Oregon	United States	97210
89	Main Line Fertility Center /ID# 153410	Bryn Mawr	Pennsylvania	United States	19010
90	Penn State University and Milton S. Hershey Medical Center /ID# 153443	Hershey	Pennsylvania	United States	17033
91	University of Pennsylvania /ID# 153203	Philadelphia	Pennsylvania	United States	19104-5502
92	Thomas Jefferson University /ID# 153319	Philadelphia	Pennsylvania	United States	19107-4414
93	Clinical Research of Philadelphia, LLC /ID# 153279	Philadelphia	Pennsylvania	United States	19114
94	Reading Hosp Clncl Trials Ofc /ID# 153475	West Reading	Pennsylvania	United States	19611
95	Medical University of South Carolina /ID# 153325	Charleston	South Carolina	United States	29425
96	Vista Clinical Research /ID# 153399	Columbia	South Carolina	United States	29201
97	Chattanooga Medical Research /ID# 153405	Chattanooga	Tennessee	United States	37404
98	WR-ClinSearch /ID# 153404	Chattanooga	Tennessee	United States	37421-1605
99	Research Memphis Associates, LLC /ID# 153322	Memphis	Tennessee	United States	38119-3895
100	Women's Health Trials /ID# 153426	Menphis	Tennessee	United States	38104
101	Access Clinical Trials, Inc. /ID# 153441	Nashville	Tennessee	United States	37203
102	Lotus Gynecology /ID# 153476	Austin	Texas	United States	78703-1448
103	Texas Health Presbyterian Hosp /ID# 153339	Dallas	Texas	United States	75231
104	UT Southwestern Medical Center /ID# 153400	Dallas	Texas	United States	75390-7208
105	Baylor Scott & White /ID# 153273	Fort Worth	Texas	United States	76104-4110
106	Willowbend Health and Wellness /ID# 153458	Frisco	Texas	United States	75035
107	Advances in Health, Inc. /ID# 153414	Houston	Texas	United States	77030
108	The Woman's Hospital of Texas /ID# 153270	Houston	Texas	United States	77054
109	FMC Science /ID# 153289	Lampasas	Texas	United States	76550
110	Clinical Trials of Texas,Inc. /ID# 153209	San Antonio	Texas	United States	78229
111	Discovery Clinical Trials-San Antonio /ID# 153315	San Antonio	Texas	United States	78258
112	Houston Ctr for Clin Research /ID# 153221	Sugar Land	Texas	United States	77479
113	Center of Reproductive Medicin /ID# 153320	Webster	Texas	United States	77598
114	Tidewater Physicians for Women /ID# 153432	Norfolk	Virginia	United States	23502
115	Eastern Virginia Med School /ID# 153380	Norfolk	Virginia	United States	23507-1627
116	Clinical Research Partners, LL /ID# 153412	North Chesterfield	Virginia	United States	23235-4722
117	Clinical Research Partners, LLC /ID# 153343	Richmond	Virginia	United States	23220-4459
118	Clinical Trials Virginia, Inc. /ID# 153419	Richmond	Virginia	United States	23225
119	Emerson Clinical Research Inst /ID# 153416	Vienna	Virginia	United States	22182
120	Virginia Mason Medical Center /ID# 153342	Seattle	Washington	United States	98101
121	Seattle Women's Health, Research, Gynecology /ID# 153306	Seattle	Washington	United States	98105
122	Victory Reproductive Care /ID# 153299	Windsor	Ontario	Canada	N8W 5R7
123	Rodriguez-Ginorio, San Juan /ID# 153328	San Juan		Puerto Rico	00917
124	School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 153329	San Juan		Puerto Rico	00935

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Dec 18, 2017
• Statistical Analysis Plan - May 24, 2018

More Information

Publications

• Simon JA, Al-Hendy A, Archer DF, Barnhart KT, Bradley LD, Carr BR, Dayspring T, Feinberg EC, Gillispie V, Hurtado S, Kim J, Liu R, Owens CD, Muneyyirci-Delale O, Wang A, Watts NB, Schlaff WD. Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas. Obstet Gynecol. 2020 Jun;135(6):1313-1326. doi: 10.1097/AOG.0000000000003869.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02925494
• Other Study ID Numbers: M12-816
• First Posted: Oct 6, 2016
• Last Update Posted: Jul 13, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: Uterine Fibroids; Elagolix; Heavy Menstrual Bleeding; Elagolix Sodium; Elagolix plus Norethindrone Acetate
• Additional relevant MeSH terms: Leiomyoma; Myofibroma; Menorrhagia; Hemorrhage; Norethindrone; Norethindrone Acetate; Estradiol

Study Results

Participant Flow

Recruitment Details	A total of 433 participants who completed the 6-month Treatment Period in pivotal studies M12-815 (NCT02654054) or M12-817 (NCT02691494) were enrolled in this extension study at 114 sites in 2 countries (US [including Puerto Rico] and Canada).
Pre-assignment Detail	A total of 433 participants were treated in this extension study and were grouped according to the treatment assignments in pivotal studies M12-815 and M12-817 and this extension study.

Arm/Group Title	Placebo->Elagolix	Placebo->Elagolix + E2/NETA	Elagolix->Elagolix	Elagolix + E2/NETA->Elagolix + E2/NETA
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg twice daily (BID) in extension study.	Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) once daily (QD) in extension study.	Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.	Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.
Period Title: Treatment Period
STARTED	59	58	98	218
COMPLETED	50	43	79	182
NOT COMPLETED	9	15	19	36
Period Title: Treatment Period
STARTED	54	47	88	184
COMPLETED	40	37	64	134
NOT COMPLETED	14	10	24	50

Baseline Characteristics

Arm/Group Title	Placebo->Elagolix	Placebo->Elagolix + E2/NETA	Elagolix->Elagolix	Elagolix + E2/NETA->Elagolix + E2/NETA	Total
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg BID in extension study.	Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.	Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.	Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.	Total of all reporting groups
Overall Participants	59	58	98	218	433
Age, Customized (Count of Participants)
25 to < 30 years	0 0%	3 5.2%	1 1%	4 1.8%	8 1.8%
30 to < 35 years	4 6.8%	2 3.4%	7 7.1%	19 8.7%	32 7.4%
35 to < 40 years	12 20.3%	10 17.2%	18 18.4%	34 15.6%	74 17.1%
40 to < 45 years	20 33.9%	21 36.2%	36 36.7%	74 33.9%	151 34.9%
45 to < 50 years	16 27.1%	16 27.6%	30 30.6%	77 35.3%	139 32.1%
>= 50 years	7 11.9%	6 10.3%	6 6.1%	10 4.6%	29 6.7%
Sex: Female, Male (Count of Participants)
Female	59 100%	58 100%	98 100%	218 100%	433 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 11.9%	7 12.1%	9 9.2%	33 15.1%	56 12.9%
Not Hispanic or Latino	52 88.1%	51 87.9%	89 90.8%	185 84.9%	377 87.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	2 0.9%	2 0.5%
Asian	2 3.4%	0 0%	1 1%	1 0.5%	4 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	43 72.9%	39 67.2%	70 71.4%	146 67%	298 68.8%
White	13 22%	19 32.8%	25 25.5%	65 29.8%	122 28.2%
More than one race	1 1.7%	0 0%	1 1%	3 1.4%	5 1.2%
Unknown or Not Reported	0 0%	0 0%	1 1%	1 0.5%	2 0.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Meeting the Criteria for Responder
Description	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 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," "requires surgery or invasive intervention for treatment of uterine fibroids," or "adverse events" were considered non-responders regardless of whether she meets the two aforementioned responder criteria or not.
Time Frame	From Month 0 (Baseline in Pivotal Study) to Final Month of Treatment Period (up through Month 6 in Extension Study)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had an assessment.

Arm/Group Title	Placebo->Elagolix	Placebo->Elagolix + E2/NETA	Elagolix->Elagolix	Elagolix + E2/NETA->Elagolix + E2/NETA
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg BID in extension study.	Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.	Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.	Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.
Measure Participants	56	54	94	206
Number [percentage of participants]	85.7 145.3%	66.7 115%	89.4 91.2%	87.9 40.3%

2. Secondary Outcome

Title	Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period
Description	Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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.
Time Frame	Month 0 (Baseline in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had an assessment at given time point.

Arm/Group Title	Placebo->Elagolix	Placebo->Elagolix + E2/NETA	Elagolix->Elagolix	Elagolix + E2/NETA->Elagolix + E2/NETA
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg BID in extension study.	Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.	Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.	Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.
Measure Participants	56	54	94	206
Study Day 1 to 28	-151.7 (184.76)	-61.7 (212.01)	-253.4 (190.07)	-186.5 (164.38)
Study Day 29 to 56	-210.9 (234.01)	-203.1 (188.15)	-249.7 (189.81)	-191.9 (166.38)
Study Day 57 to 84	-236.9 (162.33)	-209.0 (184.90)	-255.9 (175.43)	-200.6 (159.77)
Study Day 85 to 112	-235.1 (184.87)	-204.5 (177.65)	-252.0 (175.23)	-200.5 (156.85)
Study Day 113 to 140	-237.3 (234.00)	-194.5 (213.69)	-253.9 (173.50)	-192.9 (165.42)
Study Day 141 to 168	-263.8 (199.83)	-175.4 (115.43)	-279.1 (191.44)	-211.4 (165.26)
Final Month	-256.6 (194.04)	-186.4 (138.16)	-250.3 (182.09)	-205.6 (151.55)

3. Secondary Outcome

Title	Percent Change From Baseline in MBL Volume For Each 28-Day Interval and Final Month of the Treatment Period
Description	Baseline MBL volume was defined as the mean of total MBL volume from all the qualified menstrual cycles during the Screening Period of the pivotal study, 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.
Time Frame	Month 0 (Baseline in Pivotal Study), Extension Study: Day 1 to 28, Day 29 to 56, Day 57 to 84, Day 85 to 112, Day 113 to 140, Day 141 to 168, Final Month of Treatment Period (up through Month 6)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had an assessment at given time point.

Arm/Group Title	Placebo->Elagolix	Placebo->Elagolix + E2/NETA	Elagolix->Elagolix	Elagolix + E2/NETA->Elagolix + E2/NETA
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg BID in extension study.	Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.	Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.	Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.
Measure Participants	56	54	94	206
Study Day 1 to 28	-46.5 (66.57)	-28.2 (72.69)	-94.0 (24.90)	-87.7 (36.24)
Study Day 29 to 56	-87.2 (46.33)	-79.4 (41.80)	-93.3 (28.77)	-87.8 (43.17)
Study Day 57 to 84	-89.9 (37.62)	-82.9 (34.79)	-96.9 (16.88)	-90.6 (32.60)
Study Day 85 to 112	-90.3 (30.26)	-82.7 (32.76)	-95.2 (19.38)	-91.2 (28.42)
Study Day 113 to 140	-90.0 (40.38)	-75.0 (65.97)	-97.7 (13.01)	-87.5 (40.67)
Study Day 141 to 168	-91.8 (30.77)	-79.3 (32.25)	-99.2 (4.31)	-89.7 (36.67)
Final Month	-91.0 (28.74)	-78.5 (36.76)	-96.6 (18.29)	-90.8 (33.01)

4. Secondary Outcome

Title	Percentage of Participants With Suppression of Bleeding at the Final Month
Description	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.
Time Frame	Final Month of Treatment Period (up through Month 6)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had an assessment.

Arm/Group Title	Placebo->Elagolix	Placebo->Elagolix + E2/NETA	Elagolix->Elagolix	Elagolix->Elagolix + E2/NETA
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg BID in extension study.	Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.	Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.	Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.
Measure Participants	53	50	93	206
Number [percentage of participants]	88.7 150.3%	56.0 96.6%	89.2 91%	74.8 34.3%

5. Secondary Outcome

Title	Percentage of Participants With Baseline Hemoglobin Concentration ≤ 10.5 g/dL and an Increase From Baseline > 2 g/dL at Month 6 During the Treatment Period
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug, had a baseline hemoglobin concentration of <= 10.5 g/dL and had an assessment.

Arm/Group Title	Placebo->Elagolix	Placebo->Elagolix + E2/NETA	Elagolix->Elagolix	Elagolix + E2/NETA->Elagolix + E2/NETA
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg BID in extension study.	Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.	Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.	Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.
Measure Participants	17	11	28	51
Number [percentage of participants]	70.6 119.7%	36.4 62.8%	71.4 72.9%	72.5 33.3%

Adverse Events

Time Frame	From the first dose date in Study M12-816 through up to 30 days after the last dose date. Mean (SD) treatment exposure in M12-816 was 153.7 (44.55), 145.0 (49.00), 156.5 (36.27) and 157.6 (36.11) days for the Placebo->Elagolix, Placebo->Elagolix + E2/NETA, Elagolix->Elagolix, and Elagolix + E2/NETA->Elagolix + E2/NETA arms, respectively
Adverse Event Reporting Description	Treatment-emergent adverse events are presented.
Arm/Group Title	Placebo->Elagolix		Placebo->Elagolix + E2/NETA		Elagolix->Elagolix		Elagolix + E2/NETA->Elagolix + E2/NETA
Arm/Group Description	Placebo in pivotal study and elagolix 300 mg BID in extension study.		Placebo in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.		Elagolix 300 mg BID in pivotal study and elagolix 300 mg BID in extension study.		Elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in pivotal study and elagolix 300 mg BID plus E2/NETA (estradiol 1.0 mg/norethindrone acetate 0.5 mg) QD in extension study.
All Cause Mortality
	Placebo->Elagolix		Placebo->Elagolix + E2/NETA		Elagolix->Elagolix		Elagolix + E2/NETA->Elagolix + E2/NETA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		1/58 (1.7%)		0/98 (0%)		0/218 (0%)
Serious Adverse Events
	Placebo->Elagolix		Placebo->Elagolix + E2/NETA		Elagolix->Elagolix		Elagolix + E2/NETA->Elagolix + E2/NETA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/59 (1.7%)		3/58 (5.2%)		2/98 (2%)		6/218 (2.8%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/59 (1.7%)	1	0/58 (0%)	0	0/98 (0%)	0	0/218 (0%)	0
Hepatobiliary disorders
CHOLECYSTITIS ACUTE	0/59 (0%)	0	0/58 (0%)	0	1/98 (1%)	1	0/218 (0%)	0
CHOLELITHIASIS	0/59 (0%)	0	0/58 (0%)	0	1/98 (1%)	1	0/218 (0%)	0
Infections and infestations
PILONIDAL CYST	0/59 (0%)	0	0/58 (0%)	0	0/98 (0%)	0	1/218 (0.5%)	1
SEPSIS	0/59 (0%)	0	1/58 (1.7%)	1	0/98 (0%)	0	0/218 (0%)	0
Metabolism and nutrition disorders
OBESITY	0/59 (0%)	0	0/58 (0%)	0	1/98 (1%)	1	0/218 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	0/59 (0%)	0	1/58 (1.7%)	1	0/98 (0%)	0	0/218 (0%)	0
BREAST CANCER STAGE II	0/59 (0%)	0	0/58 (0%)	0	0/98 (0%)	0	1/218 (0.5%)	1
Nervous system disorders
FACIAL PARALYSIS	0/59 (0%)	0	0/58 (0%)	0	0/98 (0%)	0	1/218 (0.5%)	1
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS	0/59 (0%)	0	0/58 (0%)	0	0/98 (0%)	0	1/218 (0.5%)	1
Reproductive system and breast disorders
MENORRHAGIA	0/59 (0%)	0	0/58 (0%)	0	0/98 (0%)	0	1/218 (0.5%)	1
METRORRHAGIA	0/59 (0%)	0	1/58 (1.7%)	1	0/98 (0%)	0	0/218 (0%)	0
PELVIC PAIN	0/59 (0%)	0	0/58 (0%)	0	0/98 (0%)	0	1/218 (0.5%)	1
Surgical and medical procedures
HYSTERECTOMY	0/59 (0%)	0	0/58 (0%)	0	0/98 (0%)	0	1/218 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Placebo->Elagolix		Placebo->Elagolix + E2/NETA		Elagolix->Elagolix		Elagolix + E2/NETA->Elagolix + E2/NETA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/59 (64.4%)		26/58 (44.8%)		25/98 (25.5%)		50/218 (22.9%)
Blood and lymphatic system disorders
ANAEMIA	0/59 (0%)	0	3/58 (5.2%)	3	0/98 (0%)	0	2/218 (0.9%)	2
Gastrointestinal disorders
NAUSEA	5/59 (8.5%)	5	3/58 (5.2%)	3	2/98 (2%)	2	9/218 (4.1%)	10
Infections and infestations
NASOPHARYNGITIS	1/59 (1.7%)	2	1/58 (1.7%)	1	5/98 (5.1%)	5	9/218 (4.1%)	11
TOOTH INFECTION	2/59 (3.4%)	2	3/58 (5.2%)	3	0/98 (0%)	0	0/218 (0%)	0
URINARY TRACT INFECTION	0/59 (0%)	0	3/58 (5.2%)	3	4/98 (4.1%)	4	5/218 (2.3%)	5
Investigations
BONE DENSITY DECREASED	2/59 (3.4%)	2	2/58 (3.4%)	2	6/98 (6.1%)	6	2/218 (0.9%)	2
Musculoskeletal and connective tissue disorders
ARTHRALGIA	3/59 (5.1%)	3	2/58 (3.4%)	2	1/98 (1%)	1	3/218 (1.4%)	3
Nervous system disorders
HEADACHE	4/59 (6.8%)	4	3/58 (5.2%)	3	4/98 (4.1%)	4	12/218 (5.5%)	12
Psychiatric disorders
ANXIETY	1/59 (1.7%)	1	3/58 (5.2%)	3	1/98 (1%)	1	3/218 (1.4%)	3
MOOD SWINGS	3/59 (5.1%)	3	2/58 (3.4%)	2	1/98 (1%)	1	2/218 (0.9%)	2
Reproductive system and breast disorders
METRORRHAGIA	0/59 (0%)	0	4/58 (6.9%)	4	0/98 (0%)	0	1/218 (0.5%)	1
Skin and subcutaneous tissue disorders
ALOPECIA	3/59 (5.1%)	3	1/58 (1.7%)	1	1/98 (1%)	1	0/218 (0%)	0
NIGHT SWEATS	15/59 (25.4%)	16	4/58 (6.9%)	4	2/98 (2%)	2	7/218 (3.2%)	8
Vascular disorders
HOT FLUSH	30/59 (50.8%)	33	4/58 (6.9%)	4	3/98 (3.1%)	3	15/218 (6.9%)	15

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

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