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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03213457
Recruitment Status : Active, not recruiting
First Posted : July 11, 2017
Results First Posted : April 20, 2021
Last Update Posted : April 20, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE July 7, 2017
First Posted Date  ICMJE July 11, 2017
Results First Submitted Date  ICMJE March 24, 2021
Results First Posted Date  ICMJE April 20, 2021
Last Update Posted Date April 20, 2021
Actual Study Start Date  ICMJE July 7, 2017
Actual Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2021)
  • Co-Primary Endpoint: Percentage of Participants With a Response for Dysmenorrhea (DYS) at Months 6 and 12 Based on Daily Assessment [ Time Frame: Month 6, Month 12 ]
    Participants recorded rescue analgesic use for endometriosis-associated pain daily and DYS (pain during menstruation ) and its impact on daily activities each day of their period in an electronic diary (e-Diary). DYS was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following:
    • 0: No discomfort
    • 1: Mild discomfort but I was easily able to do the things I usually do
    • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do
    • 3: Severe pain that made it difficult to do the things I usually do.
    Pain scores and analgesic use were averaged over 35 days prior to each visit. Response was defined as a reduction of -0.92 or more from baseline in DYS as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a < 15% increase in average rescue analgesic pill count and no additional analgesic).
  • Co-Primary Endpoint: Percentage of Participants With a Response for Non-menstrual Pelvic Pain (NMPP) at Months 6 and 12 Based on Daily Assessment [ Time Frame: Month 6, Month 12 ]
    Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed NMPP and its impact on their daily activities each day in an e-Diary was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following:
    • 0: No discomfort
    • 1: Mild discomfort but I was easily able to do the things I usually do
    • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do
    • 3: Severe pain that made it difficult to do the things I usually do.
    Pain scores and analgesic use were averaged over the 35 days prior to each visit. Response was defined as a reduction of -0.55 or greater from baseline for NMPP as well as no increase in rescue analgesic use for endometriosis-associated pain (defined as a < 15% increase in average pill count of rescue analgesics and no additional analgesics).
Original Primary Outcome Measures  ICMJE
 (submitted: July 7, 2017)
  • Proportion of responders based on Dysmenorrhea (DYS) [ Time Frame: At Month 6 ]
    It is measured by the Endometriosis Daily Pain Impact scale in the e-Diary.
  • Proportion of responders based on Non-menstrual pelvic pain (NMPP) [ Time Frame: At Month 6 ]
    It is measured by the Endometriosis Daily Pain Impact scale in the e-Diary.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2021)
  • Change From Baseline in DYS at Month 12 Based on Daily Assessment [ Time Frame: Baseline, Month 12 ]
    Participants assessed DYS (pain during menstruation) and its impact on their daily activities each day of their period in an e-Diary. DYS was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following:
    • 0: No discomfort
    • 1: Mild discomfort but I was easily able to do the things I usually do
    • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do
    • 3: Severe pain that made it difficult to do the things I usually do.
    Pain scores were averaged over the 35 days prior to each visit.
  • Change From Baseline in DYS at Month 6 Based on Daily Assessment [ Time Frame: Baseline, Month 6 ]
    Participants assessed DYS (pain during menstruation) and its impact on their daily activities each day of their period in an e-Diary. DYS was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following: 0: No discomfort
    1. Mild discomfort but I was easily able to do the things I usually do
    2. Moderate discomfort or pain that made it difficult to do some of the things I usually do
    3. Severe pain that made it difficult to do the things I usually do.
    Pain scores were averaged over the 35 days prior to each visit.
  • Change From Baseline in DYS at Month 3 Based on Daily Assessment [ Time Frame: Baseline, Month 3 ]
    Participants assessed DYS (pain during menstruation) and its impact on their daily activities each day of their period in an e-Diary. DYS was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following: 0: No discomfort
    1. Mild discomfort but I was easily able to do the things I usually do
    2. Moderate discomfort or pain that made it difficult to do some of the things I usually do
    3. Severe pain that made it difficult to do the things I usually do.
    Pain scores were averaged over the 35 days prior to each visit.
  • Change From Baseline in Non-menstrual Pelvic Pain (NMPP) at Month 12 Based on Daily Assessment [ Time Frame: Baseline, Month 12 ]
    Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed NMPP and its impact on their daily activities each day in an e-Diary was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following:
    • 0: No discomfort
    • 1: Mild discomfort but I was easily able to do the things I usually do
    • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do
    • 3: Severe pain that made it difficult to do the things I usually do.
    Pain scores and analgesic use were averaged over the 35 days prior to each visit.
  • Change From Baseline in NMPP at Month 6 Based on Daily Assessment [ Time Frame: Baseline, Month 6 ]
    Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed NMPP and its impact on their daily activities each day in an e-Diary was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following:
    • 0: No discomfort
    • 1: Mild discomfort but I was easily able to do the things I usually do
    • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do
    • 3: Severe pain that made it difficult to do the things I usually do.
    Pain scores and analgesic use were averaged over the 35 days prior to each visit.
  • Change From Baseline in NMPP at Month 3 Based on Daily Assessment [ Time Frame: Baseline, Month 3 ]
    Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed NMPP and its impact on their daily activities each day in an e-Diary was measured by the 4-point Endometriosis Daily Pain Impact Diary according to the following:
    • 0: No discomfort
    • 1: Mild discomfort but I was easily able to do the things I usually do
    • 2: Moderate discomfort or pain that made it difficult to do some of the things I usually do
    • 3: Severe pain that made it difficult to do the things I usually do.
    Pain scores and analgesic use were averaged over the 35 days prior to each visit.
  • Change From Baseline to Month 6 in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 6a T-Score [ Time Frame: Baseline, Month 6 ]
    The PROMIS Fatigue Short Form 6a is self-administered and composed of 6 questions to evaluate fatigue over the past 7 days. All questions employ the following five response options: 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always. The PROMIS Fatigue 6a score is calculated as a T-score, which is a standardized score with a mean of 50 (based on the average for the United States general population) and a standard deviation (SD) of 10. Higher scores indicate higher levels of fatigue. A decrease in score (negative change from baseline) indicates improvement in fatigue.
  • Change From Baseline in Dyspareunia (DYSP) at Month 12 Based on Daily Assessment [ Time Frame: Baseline, Month 12 ]
    Participants assessed DYSP each day in an e-Diary according to the following response options:
    • 0: None; No discomfort during sexual intercourse
    • 1: Mild; Able to tolerate the discomfort during sexual intercourse
    • 2: Moderate; Intercourse was interrupted due to pain
    • 3: Severe; Avoided intercourse because of pain
    • Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse.
    Pain scores were averaged over the 35 days prior to each visit. Responses of "Not Applicable" were excluded.
  • Change From Baseline in DYSP at Month 6 Based on Daily Assessment [ Time Frame: Baseline, Month 6 ]
    Participants assessed DYSP each day in an e-Diary according to the following response options:
    • 0: None; No discomfort during sexual intercourse
    • 1: Mild; Able to tolerate the discomfort during sexual intercourse
    • 2: Moderate; Intercourse was interrupted due to pain
    • 3: Severe; Avoided intercourse because of pain
    • Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse.
    Pain scores were averaged over the 35 days prior to each visit. Responses of "Not Applicable" were excluded.
  • Change From Baseline in DYSP at Month 3 Based on Daily Assessment [ Time Frame: Baseline, Month 3 ]
    Participants assessed DYSP each day in an e-Diary according to the following response options:
    • 0: None; No discomfort during sexual intercourse
    • 1: Mild; Able to tolerate the discomfort during sexual intercourse
    • 2: Moderate; Intercourse was interrupted due to pain
    • 3: Severe; Avoided intercourse because of pain
    • Not applicable; I was not sexually active for reasons other than endometriosis or did not have sexual intercourse.
    Pain scores were averaged over the 35 days prior to each visit. Responses of "Not Applicable" were excluded.
  • Change From Baseline to Month 12 in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 6a T-Score [ Time Frame: Baseline, Month 12 ]
    The PROMIS Fatigue Short Form 6a is self-administered and composed of 6 questions to evaluate fatigue over the past 7 days. All questions employ the following five response options: 1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always. The PROMIS Fatigue 6a score is calculated as a T-score, which is a standardized score with a mean of 50 (based on the average for the United States general population) and a standard deviation (SD) of 10. Higher scores indicate higher levels of fatigue. A decrease in score (negative change from baseline) indicates improvement in fatigue.
  • Change From Baseline in Endometriosis-Associated Pain Score at Month 12 Assessed With Numeric Rating Scale (NRS) [ Time Frame: Baseline, Month 12 ]
    The NRS measured endometriosis-associated pain with and without menstruation on an 11-point scale from 0 = no pain to 10 = worst pain ever. Site staff administered the Overall Endometriosis-Associated Pain questionnaire assessing pain over a 7-day recall period, and recorded the participant's response electronically via a tablet at the time of visit. Pain scores were averaged over the 35 days prior to each visit.
  • Change From Baseline in Endometriosis-Associated Pain Score at Month 6 Assessed With NRS [ Time Frame: Baseline, Month 6 ]
    The NRS measured endometriosis-associated pain with and without menstruation on an 11-point scale from 0 = no pain to 10 = worst pain ever. Site staff administered the Overall Endometriosis-Associated Pain questionnaire assessing pain over a 7-day recall period, and recorded the participant's response electronically via a tablet at the time of visit. Pain scores were averaged over the 35 days prior to each visit.
  • Change From Baseline in Endometriosis-Associated Pain Score at Month 3 Assessed With NRS [ Time Frame: Baseline, Month 3 ]
    The NRS measured endometriosis-associated pain with and without menstruation on an 11-point scale from 0 = no pain to 10 = worst pain ever. Site staff administered the Overall Endometriosis-Associated Pain questionnaire assessing pain over a 7-day recall period, and recorded the participant's response electronically via a tablet at the time of visit. Pain scores were averaged over the 35 days prior to each visit.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2017)
  • Change from baseline in Numeric Rating Scale (NRS) [ Time Frame: From Month 0 (baseline) to Month 12 ]
    This is assessed using overall endometriosis associated pain questionnaire, 11-point Numeric Rating Scale (NRS).
  • Change from baseline in Dysmenorrhea (DYS) [ Time Frame: From Month 0 (baseline) to Month 12 ]
    It is measured by the Endometriosis Daily Pain Impact scale in the eDiary.
  • Change from baseline in Non-menstrual pelvic pain (NMPP) [ Time Frame: From Month 0 (baseline) to Month 12 ]
    It is measured by the Endometriosis Daily Pain Impact scale in the eDiary.
  • Change from baseline in analgesic use across both classes of rescue analgesics based on total pill counts [ Time Frame: From Month 0 (baseline) to Month 12 ]
    This will be assessed using e-Diary.
  • Change from baseline in dyspareunia [ Time Frame: From Month 0 (baseline) to Month 12 ]
    This will be assessed using e-Diary.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Study to Evaluate the Safety and Efficacy of Elagolix in Participants With Moderate to Severe Endometriosis-Associated Pain
Official Title  ICMJE A Phase 3 Study to Evaluate the Safety and Efficacy of Elagolix in Combination With Estradiol/Norethindrone Acetate in Subjects With Moderate to Severe Endometriosis-Associated Pain
Brief Summary The objective of this study is to evaluate safety and efficacy of elagolix in the management of moderate to severe endometriosis-associated pain in adult premenopausal female participants including the safety and efficacy of elagolix in combination with concomitant hormonal add-back therapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Endometriosis
Intervention  ICMJE
  • Drug: Estradiol/Norethindrone Acetate
    Tablets
    Other Names:
    • Activella
    • E2/NETA
  • Drug: Placebo for Elagolix
    Tablet
  • Drug: Elagolix
    Tablet
    Other Names:
    • ABT-620
    • Elagolix Sodium
    • ORILISSA
  • Drug: Placebo for E2/NETA
    Tablets
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo for elagolix administered twice daily (BID) plus placebo for estradiol/norethindrone acetate (E2/NETA) administered once daily (QD) for the 12-month placebo-controlled Treatment Period, followed by elagolix 200 mg BID plus E2/NETA 1 mg/0.5 mg QD for the remaining 36 months of the Treatment Period.
    Interventions:
    • Drug: Placebo for Elagolix
    • Drug: Placebo for E2/NETA
  • Experimental: Elagolix / Elagolix + E2/NETA
    Elagolix 200 mg BID alone for the first 6 months of the 12-month placebo-controlled Treatment Period and elagolix 200 mg BID+E2/NETA 1 mg/0.5 mg QD for the second 6 months, followed by elagolix 200 mg BID+E2/NETA 1 mg/0.5 mg QD for the remaining 36 months of the Treatment Period.
    Interventions:
    • Drug: Estradiol/Norethindrone Acetate
    • Drug: Elagolix
  • Experimental: Elagolix + E2/NETA
    Elagolix 200 mg BID + E2/NETA 1 mg/0.5 mg QD for the 12-month placebo-controlled Treatment Period, followed by elagolix 200 mg BID plus E2/NETA 1 mg/0.5 mg QD for the remaining 36 months of the Treatment Period.
    Interventions:
    • Drug: Estradiol/Norethindrone Acetate
    • Drug: Elagolix
Publications * Watts NB, Binkley N, Owens CD, Al-Hendy A, Puscheck EE, Shebley M, Schlaff WD, Simon JA. Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life. J Womens Health (Larchmt). 2021 Oct;30(10):1416-1430. doi: 10.1089/jwh.2020.8989. Epub 2021 Aug 25. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 15, 2019)
681
Original Estimated Enrollment  ICMJE
 (submitted: July 7, 2017)
700
Estimated Study Completion Date  ICMJE January 30, 2023
Actual Primary Completion Date March 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 within 10 years prior to entry into Washout or Screening.
  • Participant must agree to use only protocol specified rescue analgesics during the Screening and Treatment Periods for 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" dysmenorrhea (DYS) AND either
    2. At least 2 days of "moderate" or "severe" non-menstrual pelvic pain (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-related 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 any major depression or post-traumatic stress disorder (PTSD) within 2 years of the screening visit 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) within the last 1 year at Screening or prior to randomization on Day 1.
  • Participant has any history of osteoporosis or other metabolic bone disease or 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 2.0 or more standard deviations below normal.
  • 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 randomization on Day 1 OR
    2. a clinically significant medical condition that is anticipated to require intervention during the course of study participation (e.g., anticipated major elective surgery) OR
    3. an unstable medical condition that makes the subject an unsuitable candidate for the study in the opinion of the Investigator, (including, but not limited to, uncontrolled diabetes mellitus, uncontrolled hypertension, epilepsy requiring anti-epileptic medication, unstable angina, confirmed inflammatory bowel disease, hyperprolactinemia, clinically significant infection or injury).
  • Participant has any conditions contraindicated with use of E2/NETA.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 49 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Puerto Rico,   United States
Removed Location Countries American Samoa
 
Administrative Information
NCT Number  ICMJE NCT03213457
Other Study ID Numbers  ICMJE M14-702
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP