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Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain

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ClinicalTrials.gov Identifier: NCT02143713
Recruitment Status : Completed
First Posted : May 21, 2014
Results First Posted : September 7, 2018
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE May 19, 2014
First Posted Date  ICMJE May 21, 2014
Results First Submitted Date  ICMJE August 9, 2018
Results First Posted Date  ICMJE September 7, 2018
Last Update Posted Date September 7, 2018
Actual Study Start Date  ICMJE May 27, 2014
Actual Primary Completion Date June 22, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • Percentage of Participants With a Response for Dysmenorrhea at Month 6 Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6 ]
    Response was defined as a reduction of -0.85 or more from baseline in dysmenorrhea (pain during menstruation) 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). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic use for endometriosis-associated pain daily and dysmenorrhea and its impact on daily activities each day of their period in an electronic diary (e-Diary). Dysmenorrhea was assessed 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.
    Analgesic use and pain scores were averaged over the 35 days prior to each visit.
  • Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Month 6 Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6 ]
    Response was defined as a reduction of −0.43 or greater from baseline for non-menstrual pelvic pain 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). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options:
    • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2014)
  • Endometriosis-Associated Pain [ Time Frame: Month 6 of Treatment Period ]
    Proportion of responders based on reduction from baseline in study M12-671 (NCT 01931670)
  • Bone Mineral Density (DXA scan) [ Time Frame: Month 6 of Treatment Period ]
    Change from Baseline in Study M12-671 (NCT 01931670)
  • Transvaginal Ultrasound (TVU) [ Time Frame: Month 6 of Treatment Period ]
    Change form Baseline in study M12-671 (NCT 01931670)
  • Bone Mineral Density (DXA scan) [ Time Frame: Month 6 of Follow-up Period ]
    Change from Baseline in Study M12-671 (NCT 01931670)
  • Bone Mineral Density (DXA scan) [ Time Frame: Month 12 of Follow-up Period ]
    Change from Baseline in Study M12-671 (NCT01931670)
Change History Complete list of historical versions of study NCT02143713 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • Percentage of Participants With a Response for Dysmenorrhea at Each Month Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5 ]
    Response was defined as a reduction of -0.85 or more from baseline in dysmenorrhea (pain during menstruation) 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). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic use for endometriosis-associated pain daily and dysmenorrhea and its impact on daily activities each day of their period in an electronic diary (e-Diary). Dysmenorrhea was assessed 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.
    Analgesic use and pain scores were averaged over the 35 days prior to each visit.
  • Percentage of Participants With a Response for Non-menstrual Pelvic Pain at Each Month Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, and 5 ]
    Response was defined as a reduction of −0.43 or greater from baseline for non-menstrual pelvic pain 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). The response threshold represents a clinically meaningful response that was determined in pivotal Study M12-671. Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options:
    • 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.
  • Percentage of Participants With a Response for Dyspareunia at Each Month Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6 ]
    Response was defined as a reduction of −0.29 or more from baseline in dyspareunia (pain during sexual intercourse) 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 analgesics). Participants recorded rescue analgesic medication for endometriosis-associated pain and assessed dyspareunia each day in an e-Diary. Dyspareunia was assessed according to the following:
    • 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 and analgesic use were averaged over the 35 days prior to each visit. Responses of "Not Applicable" were excluded.
  • Percent Change From Baseline in Dysmenorrhea Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6 ]
    Participants assessed dysmenorrhea (pain during menstruation) and its impact on their daily activities each day of their period in an e-Diary according to the following response options:
    • 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.
  • Percent Change From Baseline in Non-menstrual Pelvic Pain Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6 ]
    Participants assessed non-menstrual pelvic pain and its impact on their daily activities each day in an e-Diary according to the following response options:
    • 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.
  • Percent Change From Baseline in Dyspareunia Based on Daily Assessment [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6 ]
    Participants assessed dyspareunia 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 Any Rescue Analgesic Use [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6 ]
    Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Any rescue analgesic use (NSAID and/or opioid) was calculated as the total number of pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day.
  • Change From Baseline in NSAID Rescue Analgesic Use [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6 ]
    Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. NSAID rescue analgesic use was calculated as the total number of NSAID pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day.
  • Change From Baseline in Opioid Rescue Analgesic Use [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 6 ]
    Permitted rescue analgesics varied by country and were limited to non-steroidal anti-inflammatory drugs (NSAID) (naproxen 500 mg), or opioid analgesics (hydrocodone 5 mg + acetaminophen 300 mg or 325 mg, or codeine 30 mg + acetaminophen 300 mg, or codeine 30 mg, or tramadol 37.5 mg + acetaminophen 325 mg). Use of rescue analgesic medications taken for endometriosis-associated pain was recorded by the participant daily in the e-Diary as the total number of pills/tablets of each type taken within a 24-hour period. Opioid rescue analgesic use was calculated as the total number of opioid pills divided by the number of days in the window (i.e. average daily pill count) over the 35-day window prior to and including the reference study day.
  • Percent Change From Baseline in Endometriosis-Associated Pain Score Assessed With Numeric Rating Scale (NRS) [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 2, 3, 4, 5, and 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. Participants were asked to assess their endometriosis pain over the past 24 hours at it's worst at approximately the same time every day in the e-Diary. Pain scores were averaged over the 35 days prior to each visit.
  • Percentage of Participants With a PGIC Response of Much Improved or Very Much Improved [ Time Frame: Months 1, 2, 3, 4, 5, and 6 ]
    The Patient Global Impression of Change (PGIC) is a questionnaire-based assessment of the change in endometriosis pain since the initiation of study drug. The participant was asked to select from one of seven response categories:
    1. Very Much Improved
    2. Much Improved
    3. Minimally Improved
    4. Not Changed
    5. Minimally Worse
    6. Much Worse
    7. Very Much Worse
  • Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Pain Dimension [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 3, and 6 ]
    The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and includes pain, control and powerlessness, emotional well-being, social support, and self-image, and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis. Each question in the core questionnaire is scored on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always. The pain dimension consists of 11 questions. The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life.
  • Change From Baseline in Endometriosis Health Profile-30 (EHP-30) Sexual Intercourse Dimension [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and months 1, 3, and 6 ]
    The EHP-30 is an instrument to measure health-related quality of life in women with endometriosis. The EHP-30 consists of two parts: a core questionnaire containing 5 scales that are applicable to all women with endometriosis and a modular part containing 6 scales which do not necessarily apply to all women with endometriosis; only 1 modular questionnaire (sexual intercourse [5 items]) was used in this study. The Sexual Intercourse dimension consists of 5 questions, each answered on the following scale: 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Always, or Not Applicable (not scored). The dimension score ranges from 0 to 100, where 0 = best possible health status as measured by the questionnaire; 100 = worst possible health status. A negative change from baseline score indicates improvement in quality of life.
  • Change From Baseline in Health-Related Productivity Questionnaire (HRPQ): Hours of Work Lost in Workplace and Household [ Time Frame: Baseline (defined as baseline of Study M12-671 for participants who received elagolix in the pivotal study and baseline of the extension study M12-821 for participants who received placebo in the pivotal study) and Month 6 ]
    The HRPQ consists of 9 questions measuring the impact of endometriosis-associated pain and its treatment on work productivity and daily activities in the home. Absenteeism: Number of hours of intended work lost due to illness or treatment. Presenteeism: Number of hours of work where output was impacted by illness or treatments. Total hours lost is the sum of hours missed due to absenteeism plus presenteeism.
  • Number of Participants With Non-study Health Visits During the Treatment Period [ Time Frame: 6 months ]
    The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study.
  • Number of Days in Hospital During the Treatment Period [ Time Frame: 6 months ]
    The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study, including physician visits, hospitalizations and types of procedures received.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2014)
  • Clinical Laboratory Tests (standard laboratory values including hormones) [ Time Frame: Month 6 of Treatment Period ]
    Change from Baseline in Study M12-671 (NCT 01931670)
  • Number of study subjects with Adverse Events [ Time Frame: Up to Month 18 ]
  • Clinical Laboratory Tests (standard laboratory values including hormones) [ Time Frame: Month 3 of Follow-up Period ]
    Change from Baseline in Study M12-671 (NCT 01931670)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Global Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Women With Moderate to Severe Endometriosis-associated Pain
Official Title  ICMJE Extension Study to Evaluate the Long-Term Safety and Efficacy of Elagolix in Subjects With Moderate to Severe Endometriosis-Associated Pain
Brief Summary A randomized study evaluating the continued safety and efficacy of elagolix in the management of moderate to severe endometriosis associated pain in adult pre-menopausal women who completed 6 months treatment in pivotal Study M12-671 (NCT01931670).
Detailed Description

The study consists of 2 periods: a 6 month Treatment Period and a post treatment follow-up period of up to 12 months.

Participants who received elagolix in the pivotal study who met all entry criteria continued to receive the same dose, either elagolix 150 mg once daily (QD) or elagolix 200 mg twice daily (BID) for up to an additional 6 months in this extension study; participants who received placebo in the pivotal study were randomized in a 1:1 ratio to receive either elagolix 150 mg QD or elagolix 200 mg BID for up to 6 months.

An electronic diary will be used to collect endometriosis-associated pain, uterine bleeding, and analgesic medication use for endometriosis associated pain on a daily basis.

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: Elagolix
Elagolix tablets administered orally
Other Name: Orilissa™
Study Arms  ICMJE
  • Experimental: Elagolix 150 mg QD
    Participants received elagolix 150 mg tablets once a day (QD) for 6 months.
    Intervention: Drug: Elagolix
  • Experimental: Elagolix 200 mg BID
    Participants received elagolix 200 mg tablets twice a day (BID) for 6 months.
    Intervention: Drug: Elagolix
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: January 3, 2018)
496
Original Estimated Enrollment  ICMJE
 (submitted: May 19, 2014)
500
Actual Study Completion Date  ICMJE May 23, 2017
Actual Primary Completion Date June 22, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject has completed the 6-Month Treatment Period in pivotal study M12-671.
  • Agrees to use required birth control methods during the study through Month 6 of the Post-treatment Follow-up period

Exclusion Criteria:

  • Clinically significant gynecological condition
  • Bone mineral density (BMD) loss greater than or equal to 8 percent in the spine, femoral neck or total hip
  • Plans to become pregnant in the next 18 months
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Argentina,   Australia,   Austria,   Brazil,   Czech Republic,   Czechia,   Hungary,   Italy,   New Zealand,   Poland,   South Africa,   Spain,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02143713
Other Study ID Numbers  ICMJE M12-821
2013-001047-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
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: Undecided
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date March 2018

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