SPIRIT EXTENSION: Efficacy and Safety Extension Study of Relugolix in Women With Endometriosis-Associated Pain

Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain. The least squares (LS) mean was presented by pivotal study treatment group and by visit.

Assessed using the pain domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain. The least squares (LS) mean was presented by pivotal study treatment group and by visit.

Assessed using the Pain Domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain.

Assessed using the Pain Domain of the EHP-30 questionnaire. The EHP-30 questionnaire was completed on an electronic tablet (eTablet) device. Participants reported the frequency (never, rarely, sometimes, often, and always) with which they had difficulty with activities such as standing, sitting, walking, sleeping, and performing jobs around the house because of pain. The Pain Domain normalized scores ranged from 0 to 100, with higher scores denoting greater functional impact of pain.

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

The PGIC for dysmenorrhea is a 1-item questionnaire designed to assess participant's impression of change in the severity of pain during their menstrual cycle. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse.

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants rated their pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Assessed using an NRS score (11-point scale) for overall pain recorded daily in an electronic diary. Participants rated their overall pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Assessed using an NRS score (11-point scale) for overall pain recorded daily in an electronic diary. Participants rated their overall pelvic pain on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Assessed based on usage of study-specified opioids for endometriosis-associated pain recorded daily in an electronic diary. Participants received protocol-specified opioids for treatment of endometriosis-associated pain as needed for pain but not prophylactically.

Assessed based on usage of study-specified analgesics for endometriosis-associated pain recorded daily in an electronic diary. Participants received protocol-specified analgesics for treatment of endometriosis-associated pain as needed for pain but not prophylactically.

The PGIC for NMPP is a 1-item questionnaire designed to assess participant's impression of change in the severity of pain when they are not menstruating. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse.

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants were to report whether they had vaginal sexual intercourse and rated their level of pelvic pain during intercourse on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

Assessed using an NRS score (11-point scale) for pain recorded daily in an electronic diary. Participants were to report whether they had vaginal sexual intercourse and rated their level of pelvic pain during intercourse on a scale from 0 to 10, with 0 indicating no pain and 10 indicating pain as bad as you can imagine. The LS mean was presented by pivotal study treatment group and by visit.

The PGIC for dyspareunia is a 1-item questionnaire designed to assess participant's impression of change in the severity of their pain during sexual intercourse. The questionnaire used a 7-point response scale: much better, better, a little better, the same, a little worse, worse, or much worse.

Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an electronic diary. Participants were to report their pain during intercourse daily using the following response options: Severe (avoids intercourse because of pain), Moderate (intercourse painful to the point of causing interruption), Mild (tolerated pain), No pain (no pain during intercourse), or No intercourse (no intercourse for other reasons). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.

Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dyspareunia recorded daily in an electronic diary. Participants were to report their pain during intercourse daily using the following response options: Severe (avoids intercourse because of pain), Moderate (intercourse painful to the point of causing interruption), Mild (tolerated pain), No pain (no pain during intercourse), or No intercourse (no intercourse for other reasons). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.

The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant's impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS mean was presented by pivotal study treatment group and by visit.

The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant's impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4). The LS mean was presented by pivotal study treatment group and by visit.

The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant's impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4).

The PGA for pelvic pain severity is a 1-item questionnaire designed to assess participant's impression of the severity of their pain. The questionnaire used a 5-point response scale; each response was given a numerical score: absent (0), mild (1), moderate (2), severe (3), or very severe (4).

The PGA for functional impairment is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities. The participants responded to the question: "How much were your daily activities limited by endometriosis over the last 4 weeks?" using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4). The LS mean was presented by pivotal study treatment group and by visit.

The PGA for functional impairment is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities. The participants responded to the question: "How much were your daily activities limited by endometriosis over the last 4 weeks?" using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4). The LS mean was presented by pivotal study treatment group and by visit.

The PGA for functional impairment is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities. The participants responded to the question: "How much were your daily activities limited by endometriosis over the last 4 weeks?" using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4).

The PGA for functional impairment is a 1-item questionnaire designed to assess participant's impression of how their pain affected their usual activities. The participants responded to the question: "How much were your daily activities limited by endometriosis over the last 4 weeks?" using a 5-point response scale; each response was given a numerical score: not at all (0), minimally (1), moderately (2), significantly (3), or very significantly (4).

Assessed using the following non-pain domains of the EHP-30 questionnaire: Control and Powerlessness (questions 12 through 17), Emotional Well-Being (questions 18 through 23), Social Support (questions 24 through 27), and Self-Image (questions 28 through 30). The score for each domain ranged from 0 to 100. Higher scores represent a greater impact of endometriosis. The LS mean was presented by pivotal study treatment group and by visit.

Assessed using the following non-pain domains of the EHP-30 questionnaire: Control and Powerlessness (questions 12 through 17), Emotional Well-Being (questions 18 through 23), Social Support (questions 24 through 27), and Self-Image (questions 28 through 30). The score for each domain ranged from 0 to 100. Higher scores represent a greater impact of endometriosis. The LS mean was presented by pivotal study treatment group and by visit.

Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an electronic diary. Participants were to report their pain as related to functional impairment daily in an electronic diary using the following response options: Severe (in bed all day, incapacitation), Moderate (in bed part of the day, some loss of work efficiency), Mild (some loss of work efficiency), No pain (no pain associated with menstruation during past 24 hours), or did not menstruate during the past 24 hours. Participants gave a possible score of 0 (no pain) to 4 (did not menstruate). The LS mean was presented by pivotal study treatment group and by visit.

Assessed using the participant-modified Biberoglu and Behrman 5-point scale for dysmenorrhea recorded daily in an electronic diary. Participants were to report their pain as related to functional impairment daily in an electronic diary using the following response options: Severe (in bed all day, incapacitation), Moderate (in bed part of the day, some loss of work efficiency), Mild (some loss of work efficiency), No pain (no pain associated with menstruation during past 24 hours), or did not menstruate during the past 24 hours. Participants gave a possible score of 0 (no pain) to 4 (did not menstruate). The LS mean was presented by pivotal study treatment group and by visit.

Assessed using the participant-modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an electronic diary. Participants reported their pain daily in an electronic diary using the following response options: Severe (requires strong analgesics), Moderate (noticeable pelvic pain), Mild (occasional pelvic pain), or No pain (no pain during past 24 hours). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.

Assessed using the participant-modified Biberoglu and Behrman 4-point scale for pelvic pain recorded daily in an electronic diary. Participants reported their pain daily in an electronic diary using the following response options: Severe (requires strong analgesics), Moderate (noticeable pelvic pain), Mild (occasional pelvic pain), or No pain (no pain during past 24 hours). Participants gave a possible score of 0 (no pain) to 3 (severe). The LS mean was presented by pivotal study treatment group and by visit.

Assessed by dual-energy X-ray absorptiometry (DXA) scan at lumbar spine, total hip, and femoral neck (same leg for each participant) at each designated time point. All participants who completed treatment or terminated from the study early were required to return for a 6-month post-treatment follow-up (PTFU) and a 12-month PTFU DXA scan (except if participant was beyond 14 months from last day on treatment). Participants were also to have clinical laboratory evaluations (vitamin D, thyroid stimulating hormone, parathyroid hormone, creatinine, calcium, and phosphorous) at the 6-month and 12-month PTFU only if the PTFU DXA scans showed a bone loss of ≥3% at the lumbar spine and/or total hip compared with the parent study baseline.

Assessed by dual-energy X-ray absorptiometry (DXA) scan at lumbar spine, total hip, and femoral neck (same leg for each participant) at each designated time point. All participants who completed treatment or terminated from the study early were required to return for a 6-month post-treatment follow-up (PTFU) and a 12-month PTFU DXA scan (except if participant was beyond 14 months from last day on treatment). Participants were also to have clinical laboratory evaluations (vitamin D, thyroid stimulating hormone, parathyroid hormone, creatinine, calcium, and phosphorous) at the 6-month and 12-month PTFU only if the PTFU DXA scans showed a bone loss of ≥3% at the lumbar spine and/or total hip compared with the parent study baseline.

Blood samples were collected from participants for estradiol measurements at each specified timepoints. Estradiol concentrations were measured using an immuno-enzymatic assay based on a commercially available kit.

Blood samples were collected from participants for estradiol measurements at each specified timepoints. Estradiol concentrations were measured using an immuno-enzymatic assay based on a commercially available kit.