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

Phase 3TerminatedNCT03343067

AbbVie11 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Endometriosis

Interventions

elagolixDRUG

Tablets

estradiol/norethindrone acetate (E2/NETA)DRUG

Capsules

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 49 Years

Medical Language ↔ Plain English

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

Locations (37)

Outcomes

Primary Outcomes

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.

Time frame: Month 6

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.

Time frame: Month 6

Secondary Outcomes

Change From Baseline in DYS at Month 6

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 0 (baseline), Month 6

Change From Baseline in Daily Diary Endometriosis-Associated Pain Score Via Numeric Rating Scale (NRS) at Month 6

Data from ClinicalTrials.gov

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Pinnacle Research Group /ID# 202016

Anniston, Alabama, United States

Noble Clinical Research /ID# 170628

Tucson, Arizona, United States

Lynn Institute of the Ozarks /ID# 165052

Little Rock, Arkansas, United States

SC Clinical Research /ID# 165049

Garden Grove, California, United States

Marvel Clinical Research /ID# 169633

Huntington Beach, California, United States

Health care Affiliates Medical Group /ID# 165048

Santa Ana, California, United States

Western States Clinical Res /ID# 169809

Wheat Ridge, Colorado, United States

Nova Clinical Research, LLC /ID# 202227

Bradenton, Florida, United States

Midland Florida Clinical Research Center /ID# 201327

DeLand, Florida, United States

Southeastern Integrated Med /ID# 203109

Gainesville, Florida, United States

...and 27 more locations

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.

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 6

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.

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

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.

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

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.

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Change From Baseline Over Time in Monthly Average NMPP Pain Score

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Change From Baseline Over Time in Monthly Average Dyspareunia Pain Score

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Change From Baseline Over Time in Monthly Average Daily Diary Endometriosis-Associated Pain Score Via NRS

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Percent Change From Baseline to Each Month During the Treatment Period for DYS

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Percent Change From Baseline to Each Month During the Treatment Period for NMPP

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Percent Change From Baseline to Each Month During the Treatment Period for Dyspareunia

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

Percent Change From Baseline to Each Month During the Treatment Period for Daily Diary Endometriosis-Associated Pain Score Via NRS

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

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.

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

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.

Time frame: Months 1, 2, 3, 4, 5, 6

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).

Time frame: Months 1, 2, 3, 4, 5, 6

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.

Time frame: Month 0 (baseline), Months 1, 2, 3, 4, 5, 6

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.

Time frame: Month 0 (baseline), Months 3, 6

EHP-30 Scores Over Time: Control and Powerlessness

Time frame: Month 0 (baseline), Months 3, 6

EHP-30 Scores Over Time: Emotional Well-Being

Time frame: Month 0 (baseline), Months 3, 6

EHP-30 Scores Over Time: Social Support

Time frame: Month 0 (baseline), Months 3, 6

EHP-30 Scores Over Time: Self-Image

Time frame: Month 0 (baseline), Months 3, 6

EHP-30 Scores Over Time: Sexual Intercourse

Time frame: Month 0 (baseline), Months 3, 6

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).

Time frame: Month 0 (baseline), Months 3, 6

EQ-5D-5L Scores Over Time: Self-Care

Time frame: Month 0 (baseline), Months 3, 6

EQ-5D-5L Scores Over Time: Usual Activities

Time frame: Month 0 (baseline), Months 3, 6

EQ-5D-5L Scores Over Time: Pain/Discomfort

Time frame: Month 0 (baseline), Months 3, 6

EQ-5D-5L Scores Over Time: Anxiety/Depression

Time frame: Month 0 (baseline), Months 3, 6

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).

Time frame: Month 0 (baseline), Months 3, 6

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.

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 0 (baseline), Month 6

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.

Time frame: Month 0 (baseline), Months 3, 6

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).

Time frame: Month 0 (baseline), Month 6