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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

The Health Resource Use Questionnaire (HRUQ) was used to collect information on non-study-related health visits that participants had during the study.

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.