A Study to Evaluate the Safety and Efficacy of Elagolix for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03886220
• Collaborator: (none)
• Enrollment: 82
• Locations: 48
• Arms: 2
• Actual Duration (Months): 24.5
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main objective of this study is to assess safety and efficacy of elagolix compared to placebo in reducing heavy menstrual bleeding (HMB) associated with uterine fibroids in premenopausal women. The primary hypothesis is that elagolix, compared to placebo, reduces HMB associated with uterine fibroids in premenopausal women.

Condition or Disease	Intervention/Treatment	Phase
Uterine Fibroids	Drug: Elagolix; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4 Study to Evaluate the Safety and Efficacy of Elagolix for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women
• Actual Study Start Date: Apr 12, 2019
• Actual Primary Completion Date: Mar 31, 2021
• Actual Study Completion Date: Apr 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elagolix 150 mg Elagolix 150 mg once daily (QD)	Drug: Elagolix; Oral; Tablet; Other Names: ABT-620 elagolix sodium Orilissa
Experimental: Placebo Placebo QD	Drug: Placebo; Oral; Tablet

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Were Responders With Menstrual Blood Loss (MBL) Volume < 80 mL at Final Month and >= 50% Reduction in MBL Volume From Baseline to the Final Month [From Month 0 (Baseline) to Final Month (up to Month 6)]

   Responders were defined as participants meeting the following 2 conditions: menstrual blood loss (MBL) volume < 80 mL at the Final Month (defined as the last 28 days prior to and including the last dose day), and 50% or greater reduction in MBL volume from Baseline to the Final Month. Participants whose primary reason for prematurely discontinuing study drug was "lack of efficacy," or "requires surgery or invasive intervention for treatment of uterine fibroids" were considered as non-responders. MBL was measured by the alkaline hematin method.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participant at the time of screening has a diagnosis of uterine fibroids documented by a pelvic ultrasound [transabdominal ultrasound (TAU) and transvaginal ultrasound (TVU)].

• Participant has HMB associated with uterine fibroids as evidenced by menstrual blood loss (MBL) > 80 mL during 1 menses in screening as measured by the alkaline hematin method.

• Participant has negative urine and/or serum pregnancy test in Washout (if applicable) and/or Screening and just prior to first dose.

• Participant has an adequate endometrial biopsy performed during Screening, the results of which show no clinical significant endometrial pathology.

Exclusion Criteria:

• Participant has screening pelvic ultrasound or saline infusion sonohysterography (SIS) or magnetic resonance imaging (MRI; if SIS is unevaluable), results that show a clinically significant gynecological disorder.

• Participant has history of osteoporosis, osteopenia, or other metabolic bone disease.

• Participant has clinically significant abnormalities in clinical chemistry, hematology, or urinalysis.

• Participant has a history of major depression or post-traumatic stress disorder (PTSD) episode within 2 years of screening, OR a history of other major psychiatric disorder at any time (e.g., schizophrenia, bipolar disorder).

• Participant is using any systemic corticosteroids for over 14 days within 3 months prior to Screening or is likely to require treatment with systemic corticosteroids during the course of the study. Over the counter and prescription topical, inhaled, intranasal or intra-articular injectable (for occasional use) corticosteroids are allowed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ACCEL Research Sites /ID# 209714	Birmingham	Alabama	United States	35218
2	University of Alabama at Birmingham - Women's and Infant's Center /ID# 209581	Birmingham	Alabama	United States	35294-7333
3	Unity Health- Searcy Medical Center /ID# 210905	Searcy	Arkansas	United States	72143-4802
4	Grossmont Ctr Clin Research /ID# 217690	La Mesa	California	United States	91942
5	Women's Health Care Research Corp /ID# 211472	San Diego	California	United States	92111-3738
6	Alliance for Multispecialty Research (AMR) - Fort Myers /ID# 213764	Fort Myers	Florida	United States	33912
7	Caceres Specialized Gynecology /ID# 214956	Kissimmee	Florida	United States	34741
8	LCC Medical Research Institute /ID# 213765	Miami	Florida	United States	33126
9	Genoma Research Group, Inc /ID# 213771	Miami	Florida	United States	33165
10	A Premier Medical Research of FL /ID# 214947	Orange City	Florida	United States	32763-2833
11	GCP Clinical Research, LLC /ID# 218742	Tampa	Florida	United States	33609-3588
12	Comprehensive Clinical Trials LLC /ID# 217177	West Palm Beach	Florida	United States	33409
13	Georgia Research for Women /ID# 211321	Atlanta	Georgia	United States	30312-1200
14	Atlanta Women's Research Institute /ID# 217745	Atlanta	Georgia	United States	30342
15	Medisense Inc /ID# 217750	Atlanta	Georgia	United States	30363
16	Women's Health of Augusta /ID# 214995	Augusta	Georgia	United States	30901-2775
17	Midtown OBGYN North /ID# 209391	Columbus	Georgia	United States	31909-5715
18	Journey Medical Research Institute - Snellville /ID# 217309	Snellville	Georgia	United States	30078-6191
19	Affinity Clinical Research /ID# 215252	Oak Brook	Illinois	United States	60523-1245
20	Clinical Trials Management, LLC - Covington /ID# 215020	Covington	Louisiana	United States	70433
21	Southern Clinical Research A /ID# 213732	Metairie	Louisiana	United States	70001
22	Johns Hopkins University /ID# 211135	Baltimore	Maryland	United States	21287
23	NECCR Fall River LLC /ID# 215009	Fall River	Massachusetts	United States	02720-2972
24	Excel Clinical Research /ID# 215936	Las Vegas	Nevada	United States	89109
25	Manhattan Medical Research /ID# 213753	New York	New York	United States	10016-6023
26	Upstate Clinical Research Associates /ID# 215156	Williamsville	New York	United States	14221-6046
27	M3 Wake Research Inc. /ID# 215166	Raleigh	North Carolina	United States	27612-8106
28	Carolina Medical Trials - Winston-Salem /ID# 215027	Winston-Salem	North Carolina	United States	27103-4109
29	Legacy Medical Group-Gynecologic Oncology /ID# 211016	Portland	Oregon	United States	97210-2900
30	Clinical Research of Philadelphia, LLC /ID# 213741	Philadelphia	Pennsylvania	United States	19114
31	Reading Hospital Clinical Trials Office /ID# 213763	West Reading	Pennsylvania	United States	19611
32	Clinical Trials of SC /ID# 210204	Charleston	South Carolina	United States	29406
33	Chattanooga Medical Research /ID# 215294	Chattanooga	Tennessee	United States	37404
34	WR-Medical Research Center of Memphis LLC /ID# 213756	Memphis	Tennessee	United States	38120-8328
35	Access Clinical Trials, Inc. /ID# 215357	Nashville	Tennessee	United States	37203
36	Signature Gyn Services /ID# 213883	Fort Worth	Texas	United States	76104
37	FMC Science, LLC - OB/GYN - Georgetown /ID# 211164	Georgetown	Texas	United States	78626-8185
38	University of Texas (UT) Health Women's Research Center at Memorial City /ID# 215193	Houston	Texas	United States	77024-2515
39	Advances in Health, Inc. /ID# 215847	Houston	Texas	United States	77030
40	Clinical Trials of Texas, Inc /ID# 213768	San Antonio	Texas	United States	78229
41	Discovery Clinical Trials-San Antonio /ID# 214996	San Antonio	Texas	United States	78258
42	Storks Research, LLC /ID# 211146	Sugar Land	Texas	United States	77479-1285
43	Houston Ctr for Clin Research /ID# 215138	Sugar Land	Texas	United States	77479
44	Seattle Clinical Research Center /ID# 210853	Seattle	Washington	United States	98105
45	North Spokane Women's Health /ID# 209889	Spokane	Washington	United States	99207
46	Emanuelli Research & Development Center LLC /ID# 212715	Arecibo		Puerto Rico	00612
47	Puerto Rico Medical Research /ID# 212841	Ponce		Puerto Rico	00717
48	Mindful Medical Research /ID# 212496	San Juan		Puerto Rico	00918-3756

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: ABBVIE INC., AbbVie

Study Documents (Full-Text)

• Study Protocol - Jun 12, 2020
• Statistical Analysis Plan - Oct 6, 2020

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03886220
• Other Study ID Numbers: M16-824
• First Posted: Mar 22, 2019
• Last Update Posted: Mar 31, 2022
• Last Verified: Mar 1, 2022

• 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.: Yes
• Keywords provided by AbbVie: Elagolix; ABT-620; Uterine Fibroids; Heavy Menstrual Bleeding (HMB)
• Additional relevant MeSH terms: Leiomyoma; Myofibroma; Menorrhagia; Hemorrhage

Study Results

Participant Flow

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Placebo once daily (QD)	Elagolix 150 mg QD
Period Title: Treatment Period
STARTED	28	54
COMPLETED	23	42
NOT COMPLETED	5	12
Period Title: Treatment Period
STARTED	25	41
COMPLETED	23	39
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Placebo	Elagolix 150 mg	Total
Arm/Group Description	Placebo QD	Elagolix 150 mg QD	Total of all reporting groups
Overall Participants	28	54	82
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.0 (3.82)	42.0 (5.02)	42.3 (4.65)
Sex: Female, Male (Count of Participants)
Female	28 100%	54 100%	82 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 21.4%	12 22.2%	18 22%
Not Hispanic or Latino	22 78.6%	42 77.8%	64 78%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	11 39.3%	16 29.6%	27 32.9%
Black or African American	17 60.7%	37 68.5%	54 65.9%
Asian	0 0%	1 1.9%	1 1.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Were Responders With Menstrual Blood Loss (MBL) Volume < 80 mL at Final Month and >= 50% Reduction in MBL Volume From Baseline to the Final Month
Description	Responders were defined as participants meeting the following 2 conditions: menstrual blood loss (MBL) volume < 80 mL at the Final Month (defined as the last 28 days prior to and including the last dose day), and 50% or greater reduction in MBL volume from Baseline to the Final Month. Participants whose primary reason for prematurely discontinuing study drug was "lack of efficacy," or "requires surgery or invasive intervention for treatment of uterine fibroids" were considered as non-responders. MBL was measured by the alkaline hematin method.
Time Frame	From Month 0 (Baseline) to Final Month (up to Month 6)

Outcome Measure Data

Analysis Population Description

Full Analysis Set; multiple imputation.

Arm/Group Title	Placebo	Elagolix 150 mg
Arm/Group Description	Placebo QD	Elagolix 150 mg QD
Measure Participants	28	54
Number (95% Confidence Interval) [percentage of participants]	23.3 83.2%	49.4 91.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Elagolix 150 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments	P-value for test of difference between elagolix dose group and placebo is by pooling the results from a logistic regression model including treatment as the main effect and baseline MBL volume as a covariate in each dataset from multiple imputation.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.22
	Confidence Interval	(2-Sided) 95%; 1.086 to 9.546
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All-cause mortality: median of 197 days. Serious adverse events/other adverse events: from first dose of study drug through Month 7.
Arm/Group Title	Placebo		Elagolix 150 mg
Arm/Group Description	Placebo QD		Elagolix 150 mg QD
All Cause Mortality
	Placebo		Elagolix 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/54 (0%)
Serious Adverse Events
	Placebo		Elagolix 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/28 (7.1%)		0/54 (0%)
Gastrointestinal disorders
ENLARGED UVULA	1/28 (3.6%)	1	0/54 (0%)	0
Infections and infestations
COVID-19	1/28 (3.6%)	1	0/54 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Elagolix 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/28 (7.1%)		11/54 (20.4%)
Nervous system disorders
HEADACHE	1/28 (3.6%)	1	7/54 (13%)	7
Vascular disorders
HOT FLUSH	1/28 (3.6%)	1	6/54 (11.1%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.