A Study to Evaluate Safety and Efficacy of Elagolix in Participants With Endometriosis With Associated Moderate to Severe Pain

Endometriosis Clinical Trial

Official title:

A Study to Evaluate Safety and Efficacy of Elagolix Alone or Elagolix With Hormonal Add-Back in Subjects With Endometriosis With Associated Moderate to Severe Pain

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03343067
• Other study ID #: M16-383
• Status: Terminated
• Phase: Phase 3
• Start date: December 27, 2017
• Est. completion date: October 23, 2018

Study information

• Verified date: July 2019
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, dose-escalation study designed to evaluate the safety and efficacy of both elagolix alone and elagolix plus estradiol/norethindrone acetate (E2/NETA) over 24 months in the management of endometriosis with associated moderate to severe pain in premenopausal women.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: October 23, 2018
• Est. primary completion date: October 23, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• Participant is a premenopausal female 18 to 49 years of age (inclusive) at the time of Screening.

• Participant has a documented surgical diagnosis (e.g., laparoscopy or laparotomy) of endometriosis established by visualization or histology within 10 years prior to entry into Washout or Screening,

• Participant must agree to use only those rescue analgesics permitted by the protocol during the Screening and Treatment Periods for her endometriosis-associated pain.

• Participant must have the following documented in the e-Diary during the last 35 days prior to Study Day 1:

1. At least 2 days of "moderate" or "severe" DYS, AND either,

2. At least 2 days of "moderate" or "severe" NMPP and an average NMPP score of at least 1.0, OR

3. At least 4 days of "moderate" or "severe" NMPP and an average NMPP score of at least 0.5.

Exclusion Criteria:

• Participant has chronic pelvic pain that is not caused by endometriosis that requires chronic analgesic therapy, which would interfere with the assessment of endometriosis-associated pain.

• 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 or intranasal corticosteroids are allowed.

• Participant has a history of major depression or post-traumatic stress disorder (PTSD) within 2 years prior to screening or other major psychiatric disorder at any time

• Participant has a history of suicide attempts or answered "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening or prior to study drug dosing on Day 1.

• Participant has any condition that would interfere with obtaining adequate dual energy x-ray absorptiometry (DXA) measurements

• Screening DXA results of the lumbar spine (L1 - L4), femoral neck or total hip bone mineral density (BMD) corresponding to less than 2 or more standard deviations below normal (Z-score < -2.0 for participants < 40 years of age, T-score for participants >= 40 years of age).

• Participant has either

1. a newly diagnosed, clinically significant medical condition that requires therapeutic intervention (e.g., new onset hypertension) that has not been stabilized 30 days prior to enrollment on Day 1 OR

2. a clinically significant medical condition that is anticipated to required intervention during the course of study participation (e.g., anticipated major elective surgery) OR

3. an unstable medical condition that makes the participant an unsuitable candidate for the study in the opinion of the Investigator

• Participant has any conditions contraindicated with use of E2/NETA

Related Conditions & MeSH terms

• Endometriosis

Intervention

Drug:
• elagolix
Tablets
• estradiol/norethindrone acetate (E2/NETA)
Capsules

Locations

Country	Name	City	State
United States	Radiant Research, Inc /ID# 200045	Akron	Ohio
United States	Pinnacle Research Group /ID# 202016	Anniston	Alabama
United States	Montana Health Research Inst /ID# 170624	Billings	Montana
United States	Bingham Memorial Hospital /ID# 170110	Blackfoot	Idaho
United States	Nova Clinical Research, LLC /ID# 202227	Bradenton	Florida
United States	Quad Clinical Research, LLC /ID# 168294	Chicago	Illinois
United States	Quad Clinical Research, LLC /ID# 170629	Chicago	Illinois
United States	Central Ohio Clinical Research /ID# 170750	Columbus	Ohio
United States	Optimed Research /ID# 167642	Columbus	Ohio
United States	Midland Florida Clinical Research Center /ID# 201327	DeLand	Florida
United States	Southeastern Integrated Med /ID# 203109	Gainesville	Florida
United States	SC Clinical Research /ID# 165049	Garden Grove	California
United States	VitaLink Research /ID# 168401	Greenville	South Carolina
United States	VitaLink Research /ID# 170625	Greenville	South Carolina
United States	America's Adv. Wellness Center /ID# 170005	Houston	Texas
United States	Centex Studies, Inc /ID# 169897	Houston	Texas
United States	Marvel Clinical Research /ID# 169633	Huntington Beach	California
United States	Leavitt Womens Healthcare /ID# 169495	Idaho Falls	Idaho
United States	Care Partners Clinical Researc /ID# 168395	Jacksonville	Florida
United States	Excel Clinical Research /ID# 170620	Las Vegas	Nevada
United States	Lynn Institute of the Ozarks /ID# 165052	Little Rock	Arkansas
United States	Northwell health system /ID# 200162	Manhasset	New York
United States	LCC Medical Research Institute /ID# 168888	Miami	Florida
United States	Delricht Research /ID# 200219	New Orleans	Louisiana
United States	Women's Health Care, PC /ID# 165033	Newburgh	Indiana
United States	Eastern Virginia Med School /ID# 165016	Norfolk	Virginia
United States	A Premier Clinical Research of Florida, LLC /ID# 201887	Orange City	Florida
United States	ClinRx Research, LLC /ID# 201189	Plano	Texas
United States	Quad Clinical Research, LLC /ID# 200180	Saint Louis	Missouri
United States	Progressive Clinical Research /ID# 205565	San Antonio	Texas
United States	Health care Affiliates Medical Group /ID# 165048	Santa Ana	California
United States	Seattle Reproductive Medicine /ID# 171079	Seattle	Washington
United States	Fusion Clinical Research of Spartanburg /ID# 200010	Spartanburg	South Carolina
United States	GCP Clinical Research, LLC /ID# 169774	Tampa	Florida
United States	Noble Clinical Research /ID# 170628	Tucson	Arizona
United States	Triple O Research Institute /ID# 201128	West Palm Beach	Florida
United States	Western States Clinical Res /ID# 169809	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Responders at Month 6 Based on DYS Pain Scale	Proportion of responders at Month 6 based upon the scale for DYS pain scale (ranging from 0 [none] to 3 [severe]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.	Month 6
Primary	Proportion of Responders at Month 6 Based on NMPP Pain Scale	Proportion of responders at Month 6 based upon the scale for NMPP pain scale (ranging from 0 [none] to 3 [severe]) using the daily e-Diary, as well as no increased analgesic rescue use for endometriosis-associated pain.	Month 6
Secondary	Change From Baseline in DYS at Month 6	The DYS pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Month 6
Secondary	Change From Baseline in NMPP at Month 6	The NMPP pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Month 6
Secondary	Change From Baseline in Dyspareunia at Month 6	The dyspareunia pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Month 6
Secondary	Change From Baseline in Daily Diary Endometriosis-Associated Pain Score Via Numeric Rating Scale (NRS) at Month 6	The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Month 6
Secondary	Change From Baseline in Rescue Analgesic Use Across Both Classes of Rescue Analgesics (NSAIDs/Opioids) at Month 6	Based on average pill counts and assessed using the daily e-Diary. Permitted non-steroidal anti-inflammatory drugs (NSAIDs) included naproxen, ibuprofen, diclofenac, and celecoxib. Permitted opioids included hydrocodone + acetaminophen and codeine phosphate + acetaminophen.	Month 0 (baseline), Month 6
Secondary	Percentage of Participants With 30% or More Reduction From Baseline Based on the 35 Day Mean of the Daily Diary Endometriosis-Associated Pain Score Via NRS at Month 6	The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window.	Month 6
Secondary	Proportion of Responders Over Time	As assessed by change and percent change from baseline in average pain score and rescue analgesic use monthly for DYS, NMPP, dyspareunia, and Daily Diary endometriosis-associated pain score via NRS, respectively.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Proportion of Responders Over Time (Not Taking Into Consideration of Analgesic Use)	As assessed by change and percent change from Baseline in average pain score and rescue analgesic use monthly for DYS, NMPP, dyspareunia, and Daily Diary endometriosis-associated pain score via NRS, respectively.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Change From Baseline Over Time in Monthly Average DYS Pain Score	The DYS pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.; The analysis was based on a 28-day window. If a participant prematurely discontinued during the open-label period, based on the analysis window, some data might fall into Month 4 analysis.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Change From Baseline Over Time in Monthly Average NMPP Pain Score	The NMPP pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score	The dyspareunia pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS	The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Percent Change From Baseline to Each Month During the Treatment Period for DYS	The DYS pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Percent Change From Baseline to Each Month During the Treatment Period for NMPP	The NMPP pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia	The dyspareunia pain scale score ranged from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS	The NRS for overall endometriosis-associated pain ranges from 0 (none) to 10 (worst pain ever), recorded in a daily eDiary and averaged monthly based on a 35-day window. A negative change from baseline indicates improvement.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Change From Baseline Over Time in Daily Rescue Analgesic Use Across Both Classes of Rescue Analgesics	Based on average pill counts and assessed using a daily e-Diary. Permitted non-steroidal anti-inflammatory drugs (NSAIDs) included naproxen, ibuprofen, diclofenac, and celecoxib. Permitted opioids included hydrocodone + acetaminophen and codeine phosphate + acetaminophen.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Number of Analgesic Use Responders and Non-Responders Over Time	Based only on reduction of rescue analgesics used. Responders were defined as: participants with no analgesic use at screening and no analgesic use added; participants with NSAID only use at screening and NSAID dose stopped, decreased, or stable (<15% increase) and no opioid use added; participants with opioid only use at screening and opioid dose stopped, decreased, or stable (<15% increase), opioid dose stopped and NSAID substituted (any dose), opioid dose decreased and NSAID added (any dose); participants with NSAID + opioid use at screening and any of the following: NSAID dose stopped + opioid analgesic use stopped, decreased, or stable (<15% increase); NSAID dose decreased + opioid analgesic use stopped, decreased, or stable (<15% increase); NSAID dose stable (< 15% increase) + opioid analgesic use stopped, decreased, or stable (<15% increase); NSAID dose increased by >15% + opioid analgesic use stopped; NSAID dose increased by >15% + opioid analgesic dose decreases.	Months 1, 2, 3, 4, 5, 6
Secondary	Patient Global Impression of Change (PGIC) Scores Over Time	The PGIC is a 7-point response scale where participants rate their endometriosis related pain as: very much improved (1), much improved (2), minimally improved (3), not changed (4), minimally worse (5), much worse (6), very much worse (7).	Months 1, 2, 3, 4, 5, 6
Secondary	Overall Endometriosis-Associated Pain Via NRS (7-Day Recall) Scores Over Time	The endometriosis-associated pain questionnaire is an 11-point NRS assessing overall endometriosis-associated pain over a 7-day recall period. Participants assessed their endometriosis-associated pain on a scale of 0 to 10, with 0 = no pain and 10 = worst pain ever.	Month 0 (baseline), Months 1, 2, 3, 4, 5, 6
Secondary	Endometriosis Health Profile-30 (EHP-30) Scores Over Time: Pain	The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Domains used in the study included Pain, Control and Powerlessness, Well-Being, Social Support, Self-Image, and Sexual Intercourse. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.	Month 0 (baseline), Months 3, 6
Secondary	EHP-30 Scores Over Time: Control and Powerlessness	The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Domains used in the study included Pain, Control and Powerlessness, Well-Being, Social Support, Self-Image, and Sexual Intercourse. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.	Month 0 (baseline), Months 3, 6
Secondary	EHP-30 Scores Over Time: Emotional Well-Being	The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Domains used in the study included Pain, Control and Powerlessness, Well-Being, Social Support, Self-Image, and Sexual Intercourse. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.	Month 0 (baseline), Months 3, 6
Secondary	EHP-30 Scores Over Time: Social Support	The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Domains used in the study included Pain, Control and Powerlessness, Well-Being, Social Support, Self-Image, and Sexual Intercourse. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.	Month 0 (baseline), Months 3, 6
Secondary	EHP-30 Scores Over Time: Self-Image	The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Domains used in the study included Pain, Control and Powerlessness, Well-Being, Social Support, Self-Image, and Sexual Intercourse. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.	Month 0 (baseline), Months 3, 6
Secondary	EHP-30 Scores Over Time: Sexual Intercourse	The EHP-30 is a disease-specific self-administered questionnaire used to measure health-related quality of life in women with endometriosis. Domains used in the study included Pain, Control and Powerlessness, Well-Being, Social Support, Self-Image, and Sexual Intercourse. Each domain is calculated on a scale from 0 = best possible health status to 100 = worst possible health status.	Month 0 (baseline), Months 3, 6
Secondary	EuroQol-5D 5 Level (EQ-5D-5L) Scores Over Time: Mobility	The EQ-5D-5L is a health state utility instrument with 5 items that comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which is rated on 5 levels of severity (1=no problem, 2=slight problems, 3=moderate problems, 4=severe problems, 5=extreme problems) and a separate visual analog scale (VAS) indicating a participant's rating of their current health status (health today) on a scale of from 0 (worst health imaginable) to 100 (best health imaginable).	Month 0 (baseline), Months 3, 6
Secondary	EQ-5D-5L Scores Over Time: Self-Care	The EQ-5D-5L is a health state utility instrument with 5 items that comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which is rated on 5 levels of severity (1=no problem, 2=slight problems, 3=moderate problems, 4=severe problems, 5=extreme problems) and a separate visual analog scale (VAS) indicating a participant's rating of their current health status (health today) on a scale of from 0 (worst health imaginable) to 100 (best health imaginable).	Month 0 (baseline), Months 3, 6
Secondary	EQ-5D-5L Scores Over Time: Usual Activities	The EQ-5D-5L is a health state utility instrument with 5 items that comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which is rated on 5 levels of severity (1=no problem, 2=slight problems, 3=moderate problems, 4=severe problems, 5=extreme problems) and a separate visual analog scale (VAS) indicating a participant's rating of their current health status (health today) on a scale of from 0 (worst health imaginable) to 100 (best health imaginable).	Month 0 (baseline), Months 3, 6
Secondary	EQ-5D-5L Scores Over Time: Pain/Discomfort	The EQ-5D-5L is a health state utility instrument with 5 items that comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which is rated on 5 levels of severity (1=no problem, 2=slight problems, 3=moderate problems, 4=severe problems, 5=extreme problems) and a separate visual analog scale (VAS) indicating a participant's rating of their current health status (health today) on a scale of from 0 (worst health imaginable) to 100 (best health imaginable).	Month 0 (baseline), Months 3, 6
Secondary	EQ-5D-5L Scores Over Time: Anxiety/Depression	The EQ-5D-5L is a health state utility instrument with 5 items that comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which is rated on 5 levels of severity (1=no problem, 2=slight problems, 3=moderate problems, 4=severe problems, 5=extreme problems) and a separate visual analog scale (VAS) indicating a participant's rating of their current health status (health today) on a scale of from 0 (worst health imaginable) to 100 (best health imaginable).	Month 0 (baseline), Months 3, 6
Secondary	EQ-5D-5L VAS Scores Over Time: Health Today	The EQ-5D-5L is a health state utility instrument with 5 items that comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each of which is rated on 5 levels of severity (1=no problem, 2=slight problems, 3=moderate problems, 4=severe problems, 5=extreme problems) and a separate VAS indicating a participant's rating of their current health status (health today) on a scale of from 0 (worst health imaginable) to 100 (best health imaginable).	Month 0 (baseline), Months 3, 6
Secondary	Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Scores Over Time: Percent Work Missed Due to Problem	Absenteeism is presented as the mean percentage of work time missed due to health problem (as reported on the WPAI:SHP), and is calculated as: 100*number of hours of work missed due to health problem / (number of hours of work missed due to health problem + number of hours worked). WPAI is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity.	Month 0 (baseline), Month 6
Secondary	WPAI:SHP Scores Over Time: Percent Impairment While Working Due to Problem	Presenteeism (the extent to which health problem decreased productivity) is presented as the mean percentage of impairment while working due to health problem, and is calculated as: 100*scale value of question 5 on the WPAI (between 0 and 10) / 10. WPAI:SHP is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity.	Month 0 (baseline), Month 6
Secondary	WPAI:SHP Scores Over Time: Percent Overall Work Impairment Due to Problem	The mean percentage of overall work impairment due to health problem (based on the WPAI questionnaire) is presented, and is calculated as: Absenteeism (%) + extent to which health problem decreased productivity (%)* [number of hours worked / (number of hours of work missed due to health problem + number of hours worked)]. WPAI is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity.	Month 0 (baseline), Month 6
Secondary	WPAI:SHP Scores Over Time: Percent Activity Impairment Due to Problem	Activity impairment due to health problem (the extent to which health problem affected the ability to perform usual daily activities) is presented as the mean percentage of activity impairment, and is calculated as 100*scale value of WPAI question 6 (between 0 and 10) / 10. WPAI is a questionnaire used to evaluate lost productivity; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity.	Month 0 (baseline), Month 6
Secondary	Health Endometriosis Treatment Satisfaction Questionnaire (ETSQ) Scores Over Time	The 6-item ETSQ was developed to assess patient-reported satisfaction with effects on endometriosis pain, dysmenorrhea, dyspareunia, amount of bleeding tolerability and overall treatment satisfaction. The ETSQ has a 7 point response scale. The range for this scale is 0 to 36, with lower ETSQ scores reflecting lower levels of satisfaction with endometriosis treatment.	Month 0 (baseline), Months 3, 6
Secondary	PROMIS Fatigue Short Form 6a Scores Over Time	The PROMIS Fatigue Short Form 6a is self-administered and composed of 6 questions to evaluate fatigue. Possible scores range from 6 to 30, 6 = not at all (no fatigue), and 30 = very much (most fatigue).	Month 0 (baseline), Month 6