Heavy Uterine Bleeding, Uterine Fibroids
Conditions
Keywords
Uterine Fibroids, Heavy Uterine Bleeding, Elagolix, Menorrhagia, ABT-620, Leiomyomata, Elagolix sodium
Brief summary
The purpose of this proof-of-concept study is to assess the safety and effectiveness of elagolix versus placebo to reduce uterine bleeding associated with uterine fibroids, and to reduce fibroid volume and uterine volume in premenopausal women 20 to 49 years of age with heavy uterine bleeding.
Interventions
DRUGElagolix
Elagolix tablets
DRUGPlacebo
Matching placebo tablets
A continuous once-daily oral tablet containing estrogen and progestin; the low-dose strength contains estradiol 0.5 mg and norethindrone acetate 0.1 mg.
DRUGEstradiol
1.0 mg micronized estradiol tablets administered once a day
DRUGProgesterone
Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
* Subject is a pre-menopausal female 20 to 49 years of age. * Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound assessed by a central reader and verification that a fibroid present met the following criteria: * At least 1 fibroid with diameter ≥ 2 cm (longest diameter), or multiple small fibroids with a total uterine volume of ≥ 200 cm³ to ≤ 2,500 cm³ (approximately 22 weeks' gestation) as documented by a centrally read ultrasound. * Only intramural, submucosal non-pedunculated, and subserosal fibroids qualified subjects for enrollment (intracavitary pedunculated fibroids were exclusionary). * Ultrasound procedures were performed during the Screening Period, and subjects were not randomized until the investigator reviewed the central reader results verifying the inclusion requirements. * Subject has a history of regular menstrual cycles between 24 to 35 days. * Subject has heavy uterine bleeding associated with uterine fibroids as evidenced by blood loss \> 80 mL during 2 screening menstrual cycles, measured by the alkaline hematin method.
Exclusion criteria
* Subject has had a myomectomy, uterine artery embolization, or high intensity focused ultrasound for fibroid destruction within 1 year prior to randomization or any history of endometrial ablation. * Subject has a history of osteoporosis or other metabolic bone disease. * Subject shows evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including depression), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes. * Subject has a history of clinically significant condition(s) including but not limited to: * Endometriosis * Epilepsy or seizures * Type 1 diabetes * Any cancer (except basal cell carcinoma of the skin), including breast or ovarian cancer or subject has taken any systemic cancer chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) | The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) | The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero. |
| Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | The last 28 days of treatment (approximately days 61 to 90) | The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero. |
| Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) | The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero. |
| Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Baseline and Month 3 | The percentage of subjects with changes in hemoglobin concentration from Baseline to Month 3 in each of the following categories: * No change from baseline in hemoglobin * Decrease from baseline in hemoglobin ≥ -0.5 g/dL * Decrease from baseline in hemoglobin ≥ -1.0 g/dL * Increase from baseline in hemoglobin ≥ 0.5 g/dL * Increase from baseline in hemoglobin ≥ 1.0 g/dL The above categories are not all mutually exclusive or exhaustive. |
| Change in Hemoglobin Concentration From Baseline to Month 3 | Baseline and Month 3 | — |
| Change From Baseline to Month 3 in Uterine Bleeding Score | Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90) | Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2. |
| Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90) | Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2. A day with any uterine bleeding is defined as a days with a bleeding score ≥ 1. |
| Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90) | Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2. A day with moderate to very heavy bleeding is defined as a days with a bleeding score ≥ 3. |
| Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Month 3 (average bleeding score over days 61 to 90) | Participants recorded the previous days' presence and severity of bleeding every morning in an eDiary according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2. Any bleeding is defined as a score ≥ 1 and moderate to very heavy bleeding is defined as a score ≥ 3. |
| Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) | The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero. |
| Percent Change From Baseline to Month 3 in Uterine Volume | Baseline and month 3 | Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center. |
| Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued. | Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center. |
| Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | Baseline and month 3 | The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center. |
| Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued. | The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center. |
| Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Baseline and month 3 | The UFS-QoL is a disease-specific, self-administered, validated questionnaire developed to evaluate the symptoms associated with uterine fibroids and their impact on health-related quality of life (HRQL) in women with symptomatic uterine fibroids. The questionnaire consists of 37 questions, divided into 2 parts: 1) an 8-item symptom severity scale and 2) a 29-item HRQL subscale comprising 6 domains (concern, activities, energy/mood, control, self-consiousness, and sexual function), with a 4-week recall. All items are scored on a 5-point scale, ranging from not at all to a very great deal for symptom severity items and none of the time to all of the time for the HRQL items. Symptom severity and HRQL subscale scores were summed and transformed into a 0 to 100 point scale to provide a total score for each of the 2 components. Lower symptom severity scores indicate better quality of life and higher total HRQL scores indicate better quality of life. |
| Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90) | The uterine fibroid daily symptom scale is self-administered questionnaire, with a scale that ranges from 0 to 10 for the symptoms of pelvic pain, fatigue, and cramping and the impact of uterine fibroids on the subject's daily life, with 0 being the absence of the symptom and 10 being the worst severity of the symptoms or completely preventing the subjects from performing daily activities. Participants self-reported values daily in the e-Diary. |
| Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Baseline and month 3 | The Subject Intention Questionnaire (SSIQ) is a non-validated, exploratory questionnaires intended to evaluate the subject's intent to undergo surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to consider surgery) to 10 (very likely to consider surgery). SSIQ included the 2 following questions: 1. How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now? 2. How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now? |
| Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Baseline and month 3 | The Physician Intention Questionnaire (PSIQ) is a non-validated, exploratory questionnaire intended to evaluate the investigator's intent to recommend surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to recommend surgery) to 10 (very likely to recommend surgery). The PSIQ included the 2 following questions: 1. How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now? 2. How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now? |
| Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | The last 56 days of treatment (approximately days 33 to 90) | Suppression of bleeding is defined as no record of bleeding (spotting allowed) in the e-diary and no record of bleeding Indicated in the alkaline hematin data during the last 56 days of treatment. Amenorrhea is defined as no record of bleeding or spotting indicated in the e-diary and no record of bleeding or spotting Indicated in the alkaline hematin data during the last 56 days of treatment. |
Participant flow
Recruitment details
Overall, 271 female participants were enrolled into the study across 45 sites in the United States.
Pre-assignment details
Six cohorts of participants were enrolled, with 3 double-blind cohorts comparing elagolix with placebo, 2 open-label cohorts assessing add-back therapies, and 1 open-label cohort assessing the elagolix 600 mg QD dosing regimen.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 4 Elagolix 400 mg QD Participants received elagolix 400 mg once a day (QD) for 3 months. | 32 |
| Cohort 4 Elagolix 100 mg BID Participants received elagolix 100 mg twice a day (BID) for 3 months. | 33 |
| Cohort 4 Placebo Participants received placebo to elagolix BID for 3 months. | 16 |
| Cohort 1 Elagolix 200 mg BID Participants received elagolix 200 mg twice a day for 3 months. | 35 |
| Cohort 1 Placebo Participants received placebo to elagolix twice a day for 3 months. | 18 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months. | 34 |
| Cohort 5 Elagolix 600 mg QD Participants received elagolix 600 mg once a day for 3 months. | 30 |
| Cohort 2 Elagolix 300 mg BID Participants received elagolix 300 mg twice a day for 3 months. | 30 |
| Cohort 2 Placebo Participants received placebo to elagolix BID for 3 months. | 16 |
| Cohort 6 Elagolix 300 mg BID + CEP Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months. | 27 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 | 1 | 5 | 1 | 2 | 2 | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 | 1 | 3 | 1 | 1 | 0 | 1 |
| Overall Study | Noncompliance | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Received Exclusionary Medication | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Surgery or Invasive Intervention | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 Placebo | Cohort 5 Elagolix 600 mg QD | Total | Cohort 4 Elagolix 400 mg QD | Cohort 6 Elagolix 300 mg BID + CEP | Cohort 2 Placebo | Cohort 4 Placebo | Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Cohort 1 Elagolix 200 mg BID | Cohort 4 Elagolix 100 mg BID | Cohort 2 Elagolix 300 mg BID |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 4.24 | 40.8 years STANDARD_DEVIATION 5.78 | 41.8 years STANDARD_DEVIATION 5.4 | 40.8 years STANDARD_DEVIATION 5.5 | 41.6 years STANDARD_DEVIATION 5.26 | 41.6 years STANDARD_DEVIATION 7.1 | 41.1 years STANDARD_DEVIATION 5.88 | 40.9 years STANDARD_DEVIATION 6.02 | 43.1 years STANDARD_DEVIATION 4.29 | 42.1 years STANDARD_DEVIATION 5.09 | 42.6 years STANDARD_DEVIATION 5.55 |
| Age, Customized 35 to < 40 years | 2 Participants | 6 Participants | 51 Participants | 6 Participants | 6 Participants | 3 Participants | 5 Participants | 8 Participants | 5 Participants | 5 Participants | 5 Participants |
| Age, Customized < 35 years | 0 Participants | 4 Participants | 32 Participants | 7 Participants | 3 Participants | 3 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 3 Participants |
| Age, Customized 40 to < 45 years | 7 Participants | 11 Participants | 86 Participants | 8 Participants | 10 Participants | 3 Participants | 2 Participants | 10 Participants | 13 Participants | 13 Participants | 9 Participants |
| Age, Customized ≥ 45 years | 9 Participants | 9 Participants | 102 Participants | 11 Participants | 8 Participants | 7 Participants | 7 Participants | 11 Participants | 15 Participants | 12 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 33 Participants | 1 Participants | 12 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 24 Participants | 238 Participants | 31 Participants | 15 Participants | 14 Participants | 15 Participants | 33 Participants | 34 Participants | 25 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 14 Participants | 24 Participants | 200 Participants | 25 Participants | 15 Participants | 9 Participants | 13 Participants | 26 Participants | 28 Participants | 23 Participants | 23 Participants |
| Race/Ethnicity, Customized Multirace | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 5 Participants | 63 Participants | 5 Participants | 11 Participants | 6 Participants | 3 Participants | 7 Participants | 7 Participants | 10 Participants | 6 Participants |
| Sex: Female, Male Female | 18 Participants | 30 Participants | 271 Participants | 32 Participants | 27 Participants | 16 Participants | 16 Participants | 34 Participants | 35 Participants | 33 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 35 | 0 / 16 | 0 / 30 | 0 / 34 | 0 / 16 | 0 / 33 | 0 / 32 | 0 / 30 | 0 / 27 |
| other Total, other adverse events | 8 / 18 | 26 / 35 | 10 / 16 | 20 / 30 | 20 / 34 | 9 / 16 | 20 / 33 | 24 / 32 | 22 / 30 | 11 / 27 |
| serious Total, serious adverse events | 1 / 18 | 0 / 35 | 0 / 16 | 1 / 30 | 0 / 34 | 2 / 16 | 2 / 33 | 0 / 32 | 2 / 30 | 0 / 27 |
Outcome results
Primary
Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Time frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. Last observation carried forward (LOCF) imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 213.70 mL | Standard Deviation 108.08 |
| Cohort 4 Elagolix 400 mg QD | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -183.97 mL | Standard Deviation 132.19 |
| Cohort 4 Elagolix 100 mg BID | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 269.36 mL | Standard Deviation 163.17 |
| Cohort 4 Elagolix 100 mg BID | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -184.69 mL | Standard Deviation 187.05 |
| Cohort 4 Placebo | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 321.73 mL | Standard Deviation 327.57 |
| Cohort 4 Placebo | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -10.46 mL | Standard Deviation 85.04 |
| Cohort 1 Elagolix 200 mg BID | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 335.11 mL | Standard Deviation 322.68 |
| Cohort 1 Elagolix 200 mg BID | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -272.97 mL | Standard Deviation 271.39 |
| Cohort 1 Placebo | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -79.00 mL | Standard Deviation 161.33 |
| Cohort 1 Placebo | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 251.72 mL | Standard Deviation 160.29 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -192.33 mL | Standard Deviation 191.51 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 247.70 mL | Standard Deviation 177.72 |
| Cohort 5 Elagolix 600 mg QD | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -189.05 mL | Standard Deviation 151.15 |
| Cohort 5 Elagolix 600 mg QD | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 215.62 mL | Standard Deviation 122.84 |
| Cohort 2 Elagolix 300 mg BID | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 206.27 mL | Standard Deviation 125.08 |
| Cohort 2 Elagolix 300 mg BID | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -202.57 mL | Standard Deviation 127.93 |
| Cohort 2 Placebo | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 349.17 mL | Standard Deviation 424.12 |
| Cohort 2 Placebo | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -175.31 mL | Standard Deviation 342.14 |
| Cohort 6 Elagolix 300 mg BID + CEP | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Baseline | 257.99 mL | Standard Deviation 207.33 |
| Cohort 6 Elagolix 300 mg BID + CEP | Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | Change from Baseline | -216.15 mL | Standard Deviation 157.08 |
p-value: <0.00195% CI: [-295.77, -116.01]ANCOVA
p-value: <0.00195% CI: [-278.33, -101.53]ANCOVA
p-value: 0.00195% CI: [-220.18, -55.76]ANCOVA
p-value: 0.00195% CI: [-206.7, -54.6]ANCOVA
Secondary
Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding
Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2. A day with any uterine bleeding is defined as a days with a bleeding score ≥ 1.
Time frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -15.22 percentage of days | Standard Deviation 14.77 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -11.00 percentage of days | Standard Deviation 15.52 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -5.78 percentage of days | Standard Deviation 10.58 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -15.82 percentage of days | Standard Deviation 17.88 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -6.99 percentage of days | Standard Deviation 12.82 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | 3.63 percentage of days | Standard Deviation 24.74 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -15.38 percentage of days | Standard Deviation 23.21 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -16.91 percentage of days | Standard Deviation 11.13 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | -13.95 percentage of days | Standard Deviation 23.83 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding | 1.73 percentage of days | Standard Deviation 26.09 |
p-value: 0.0295% CI: [-18.9, -1.67]ANCOVA
p-value: 0.08795% CI: [-16.36, 1.13]ANCOVA
p-value: 0.04595% CI: [-17.43, -0.19]ANCOVA
p-value: 0.00295% CI: [-22.06, -5.32]ANCOVA
Secondary
Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding
Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2. A day with moderate to very heavy bleeding is defined as a days with a bleeding score ≥ 3.
Time frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -7.22 percentage of days | Standard Deviation 9.27 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -5.00 percentage of days | Standard Deviation 7.87 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -4.00 percentage of days | Standard Deviation 5.37 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -7.03 percentage of days | Standard Deviation 10.89 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -3.08 percentage of days | Standard Deviation 5.88 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -7.92 percentage of days | Standard Deviation 6.43 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -6.15 percentage of days | Standard Deviation 8.47 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -8.02 percentage of days | Standard Deviation 5.41 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -3.31 percentage of days | Standard Deviation 10.4 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding | -6.80 percentage of days | Standard Deviation 10.69 |
p-value: 0.00895% CI: [-9.56, -1.47]ANCOVA
p-value: 0.0295% CI: [-9.11, -0.8]ANCOVA
p-value: 0.19495% CI: [-9.18, 1.91]ANCOVA
p-value: 0.00195% CI: [-11.33, -3.07]ANCOVA
Secondary
Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
The Physician Intention Questionnaire (PSIQ) is a non-validated, exploratory questionnaire intended to evaluate the investigator's intent to recommend surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to recommend surgery) to 10 (very likely to recommend surgery). The PSIQ included the 2 following questions: 1. How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now? 2. How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?
Time frame: Baseline and month 3
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | -0.9 units on a scale | Standard Deviation 2.86 |
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -0.8 units on a scale | Standard Deviation 3.34 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | -1.3 units on a scale | Standard Deviation 3.31 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -1.8 units on a scale | Standard Deviation 4.37 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | -2.7 units on a scale | Standard Deviation 3.53 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -0.2 units on a scale | Standard Deviation 3.15 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | -0.8 units on a scale | Standard Deviation 1.76 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -2.2 units on a scale | Standard Deviation 2.82 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | 0.4 units on a scale | Standard Deviation 1.62 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | 0.7 units on a scale | Standard Deviation 1.11 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -1.4 units on a scale | Standard Deviation 3.08 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | -0.6 units on a scale | Standard Deviation 2.97 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -2.3 units on a scale | Standard Deviation 3.99 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | -1.3 units on a scale | Standard Deviation 3.62 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | -1.2 units on a scale | Standard Deviation 3.59 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -1.5 units on a scale | Standard Deviation 3.96 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | 0.0 units on a scale | Standard Deviation 3.25 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -0.6 units on a scale | Standard Deviation 2.81 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend myomectomy | 0.0 units on a scale | Standard Deviation 3.94 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 | Likelihood to recommend hysterectomy | -2.8 units on a scale | Standard Deviation 2.98 |
Secondary
Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
The Subject Intention Questionnaire (SSIQ) is a non-validated, exploratory questionnaires intended to evaluate the subject's intent to undergo surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to consider surgery) to 10 (very likely to consider surgery). SSIQ included the 2 following questions: 1. How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now? 2. How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?
Time frame: Baseline and month 3
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | -1.2 units on a scale | Standard Deviation 3.68 |
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | 0.0 units on a scale | Standard Deviation 4.04 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | -3.1 units on a scale | Standard Deviation 4.52 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | -1.9 units on a scale | Standard Deviation 4.19 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | 1.0 units on a scale | Standard Deviation 2.12 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | 2.0 units on a scale | Standard Deviation 3.64 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | -1.8 units on a scale | Standard Deviation 4.7 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | -0.8 units on a scale | Standard Deviation 4.91 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | -0.3 units on a scale | Standard Deviation 0.52 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | 2.3 units on a scale | Standard Deviation 5.35 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | -0.7 units on a scale | Standard Deviation 3.1 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | -1.4 units on a scale | Standard Deviation 4.34 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | -0.8 units on a scale | Standard Deviation 4.42 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | -1.7 units on a scale | Standard Deviation 4.18 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | -0.6 units on a scale | Standard Deviation 5.1 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | 0.2 units on a scale | Standard Deviation 3.65 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | 0.4 units on a scale | Standard Deviation 4.16 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | 0.0 units on a scale | Standard Deviation 1.96 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having myomectomy | 0.1 units on a scale | Standard Deviation 2.63 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 | Likelihood of having hysterectomy | -1.5 units on a scale | Standard Deviation 3.92 |
Secondary
Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores
The uterine fibroid daily symptom scale is self-administered questionnaire, with a scale that ranges from 0 to 10 for the symptoms of pelvic pain, fatigue, and cramping and the impact of uterine fibroids on the subject's daily life, with 0 being the absence of the symptom and 10 being the worst severity of the symptoms or completely preventing the subjects from performing daily activities. Participants self-reported values daily in the e-Diary.
Time frame: Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available data at baseline and month 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -1.0 units on a scale | Standard Deviation 2.27 |
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -0.5 units on a scale | Standard Deviation 1.26 |
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -1.2 units on a scale | Standard Deviation 1.31 |
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -1.1 units on a scale | Standard Deviation 1.18 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -0.0 units on a scale | Standard Deviation 2.23 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -0.2 units on a scale | Standard Deviation 2.39 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -0.4 units on a scale | Standard Deviation 1.86 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -0.7 units on a scale | Standard Deviation 2.51 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -0.6 units on a scale | Standard Deviation 1.45 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -0.3 units on a scale | Standard Deviation 1.45 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -0.5 units on a scale | Standard Deviation 1.55 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -0.8 units on a scale | Standard Deviation 1.4 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -0.6 units on a scale | Standard Deviation 1.75 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -0.6 units on a scale | Standard Deviation 1.29 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -0.9 units on a scale | Standard Deviation 1.16 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -1.0 units on a scale | Standard Deviation 1.37 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -1.2 units on a scale | Standard Deviation 0.8 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -0.5 units on a scale | Standard Deviation 1.69 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -1.0 units on a scale | Standard Deviation 1.81 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -1.4 units on a scale | Standard Deviation 1.62 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -0.9 units on a scale | Standard Deviation 1.25 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -1.2 units on a scale | Standard Deviation 1.92 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -1.1 units on a scale | Standard Deviation 1.35 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -0.9 units on a scale | Standard Deviation 1.62 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -1.0 units on a scale | Standard Deviation 2.57 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -1.1 units on a scale | Standard Deviation 1.35 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -1.7 units on a scale | Standard Deviation 2.41 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -0.9 units on a scale | Standard Deviation 2.15 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -1.0 units on a scale | Standard Deviation 1.75 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -1.3 units on a scale | Standard Deviation 1.11 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -1.5 units on a scale | Standard Deviation 1.16 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -1.2 units on a scale | Standard Deviation 1.09 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -1.0 units on a scale | Standard Deviation 2.18 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -1.2 units on a scale | Standard Deviation 1.73 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -1.0 units on a scale | Standard Deviation 2.33 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -0.5 units on a scale | Standard Deviation 2.88 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Menstrual cramping | -1.3 units on a scale | Standard Deviation 2.15 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Pelvic pain | -2.4 units on a scale | Standard Deviation 3 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Impact of uterine fibroids | -3.1 units on a scale | Standard Deviation 2.78 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores | Fatigue | -2.1 units on a scale | Standard Deviation 3.11 |
Secondary
Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
The UFS-QoL is a disease-specific, self-administered, validated questionnaire developed to evaluate the symptoms associated with uterine fibroids and their impact on health-related quality of life (HRQL) in women with symptomatic uterine fibroids. The questionnaire consists of 37 questions, divided into 2 parts: 1) an 8-item symptom severity scale and 2) a 29-item HRQL subscale comprising 6 domains (concern, activities, energy/mood, control, self-consiousness, and sexual function), with a 4-week recall. All items are scored on a 5-point scale, ranging from not at all to a very great deal for symptom severity items and none of the time to all of the time for the HRQL items. Symptom severity and HRQL subscale scores were summed and transformed into a 0 to 100 point scale to provide a total score for each of the 2 components. Lower symptom severity scores indicate better quality of life and higher total HRQL scores indicate better quality of life.
Time frame: Baseline and month 3
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available UFS-QoL data at baseline and month 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -39.0 units on a scale | Standard Deviation 24.7 |
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 35.3 units on a scale | Standard Deviation 21.87 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -33.2 units on a scale | Standard Deviation 28.17 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 29.1 units on a scale | Standard Deviation 30.96 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -19.6 units on a scale | Standard Deviation 32.8 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 16.3 units on a scale | Standard Deviation 30.43 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -31.6 units on a scale | Standard Deviation 28.87 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 36.0 units on a scale | Standard Deviation 27.91 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 18.3 units on a scale | Standard Deviation 36.66 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -21.4 units on a scale | Standard Deviation 20.63 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 28.6 units on a scale | Standard Deviation 24.12 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -20.3 units on a scale | Standard Deviation 25.35 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 29.9 units on a scale | Standard Deviation 30.72 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -36.4 units on a scale | Standard Deviation 24.74 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -44.1 units on a scale | Standard Deviation 22.12 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 33.5 units on a scale | Standard Deviation 29.42 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -12.0 units on a scale | Standard Deviation 22.49 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 11.0 units on a scale | Standard Deviation 20.9 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | Symptom severity | -39.1 units on a scale | Standard Deviation 24.09 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) | HRQL total | 33.1 units on a scale | Standard Deviation 30.34 |
Secondary
Change From Baseline to Month 3 in Uterine Bleeding Score
Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.
Time frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.50 units on a scale | Standard Deviation 0.56 |
| Cohort 4 Elagolix 100 mg BID | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.37 units on a scale | Standard Deviation 0.46 |
| Cohort 4 Placebo | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.19 units on a scale | Standard Deviation 0.33 |
| Cohort 1 Elagolix 200 mg BID | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.52 units on a scale | Standard Deviation 0.65 |
| Cohort 1 Placebo | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.22 units on a scale | Standard Deviation 0.32 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.24 units on a scale | Standard Deviation 0.47 |
| Cohort 5 Elagolix 600 mg QD | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.44 units on a scale | Standard Deviation 0.71 |
| Cohort 2 Elagolix 300 mg BID | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.53 units on a scale | Standard Deviation 0.33 |
| Cohort 2 Placebo | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.38 units on a scale | Standard Deviation 0.77 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change From Baseline to Month 3 in Uterine Bleeding Score | -0.25 units on a scale | Standard Deviation 0.64 |
p-value: 0.01195% CI: [-0.63, -0.08]ANCOVA
p-value: 0.0395% CI: [-0.59, -0.03]ANCOVA
p-value: 0.10995% CI: [-0.59, 0.06]ANCOVA
p-value: 0.00295% CI: [-0.8, -0.19]ANCOVA
Secondary
Change in Hemoglobin Concentration From Baseline to Month 3
Time frame: Baseline and Month 3
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available hemoglobin data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Change in Hemoglobin Concentration From Baseline to Month 3 | 1.18 g/dL | Standard Deviation 0.99 |
| Cohort 4 Elagolix 100 mg BID | Change in Hemoglobin Concentration From Baseline to Month 3 | 1.30 g/dL | Standard Deviation 1.19 |
| Cohort 4 Placebo | Change in Hemoglobin Concentration From Baseline to Month 3 | -0.43 g/dL | Standard Deviation 1.28 |
| Cohort 1 Elagolix 200 mg BID | Change in Hemoglobin Concentration From Baseline to Month 3 | 1.13 g/dL | Standard Deviation 1.29 |
| Cohort 1 Placebo | Change in Hemoglobin Concentration From Baseline to Month 3 | 0.28 g/dL | Standard Deviation 1.33 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Change in Hemoglobin Concentration From Baseline to Month 3 | 0.92 g/dL | Standard Deviation 0.81 |
| Cohort 5 Elagolix 600 mg QD | Change in Hemoglobin Concentration From Baseline to Month 3 | 1.40 g/dL | Standard Deviation 1.18 |
| Cohort 2 Elagolix 300 mg BID | Change in Hemoglobin Concentration From Baseline to Month 3 | 1.19 g/dL | Standard Deviation 0.85 |
| Cohort 2 Placebo | Change in Hemoglobin Concentration From Baseline to Month 3 | 0.31 g/dL | Standard Deviation 1.2 |
| Cohort 6 Elagolix 300 mg BID + CEP | Change in Hemoglobin Concentration From Baseline to Month 3 | 1.54 g/dL | Standard Deviation 1.81 |
p-value: <0.00195% CI: [0.97, 2.56]ANCOVA
p-value: <0.00195% CI: [1, 2.56]ANCOVA
p-value: 0.02495% CI: [0.13, 1.75]ANCOVA
p-value: 0.00595% CI: [0.28, 1.51]ANCOVA
Secondary
Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time frame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 53 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 43 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 7 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 48 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 11 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 42 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 56 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 69 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 7 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit | 25 percentage of participants |
p-value: 0.003Fisher Exact
p-value: 0.016Fisher Exact
p-value: 0.012Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time frame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 57 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 52 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 33 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 68 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 35 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 58 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 60 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 55 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 27 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit | 48 percentage of participants |
p-value: 0.203Fisher Exact
p-value: 0.342Fisher Exact
p-value: 0.038Fisher Exact
p-value: 0.111Fisher Exact
Secondary
Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Time frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 84 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 74 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 13 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 91 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 28 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 85 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 93 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 97 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 40 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 88 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3
Participants recorded the previous days' presence and severity of bleeding every morning in an eDiary according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale: * 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection. * 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day. * 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day. * 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours. * 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours. * 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2. Any bleeding is defined as a score ≥ 1 and moderate to very heavy bleeding is defined as a score ≥ 3.
Time frame: Month 3 (average bleeding score over days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available bleeding score data at month 3.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 37 percentage of participants |
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 27 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 57 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 40 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 93 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 87 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 47 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 28 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 82 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 94 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 31 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 78 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 15 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 27 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 26 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 7 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 80 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 73 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Any bleeding | 69 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 | Moderate to Very Heavy Bleeding | 35 percentage of participants |
Secondary
Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Time frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 84 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 74 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 13 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 85 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 17 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 85 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 93 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 97 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 33 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment | 85 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Time frame: The last 28 days of treatment (approximately days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. LOCF imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 84 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 74 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 13 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 85 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 22 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 88 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 93 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 97 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 47 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment | 88 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3
The percentage of subjects with changes in hemoglobin concentration from Baseline to Month 3 in each of the following categories: * No change from baseline in hemoglobin * Decrease from baseline in hemoglobin ≥ -0.5 g/dL * Decrease from baseline in hemoglobin ≥ -1.0 g/dL * Increase from baseline in hemoglobin ≥ 0.5 g/dL * Increase from baseline in hemoglobin ≥ 1.0 g/dL The above categories are not all mutually exclusive or exhaustive.
Time frame: Baseline and Month 3
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available hemoglobin data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 4 percentage of participants |
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 9 percentage of participants |
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 78 percentage of participants |
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 0 percentage of participants |
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 61 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 71 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 4 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 17 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 71 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 0 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 27 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 9 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 9 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 18 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 0 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 4 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 67 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 0 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 59 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 11 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 14 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 0 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 21 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 29 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 29 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 43 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 0 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 14 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 0 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 75 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 4 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 4 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 57 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 4 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 83 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 0 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 0 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 76 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 0 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 52 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 0 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 7 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 29 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 21 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 29 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -1.0 to -0.5 g/dL | 10 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Decreases from -0.5 to 0 g/dL | 5 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | No Change | 5 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 1.0 g/dL | 62 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 | Increase ≥ 0.5 g/dL | 71 percentage of participants |
Secondary
Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment
Suppression of bleeding is defined as no record of bleeding (spotting allowed) in the e-diary and no record of bleeding Indicated in the alkaline hematin data during the last 56 days of treatment. Amenorrhea is defined as no record of bleeding or spotting indicated in the e-diary and no record of bleeding or spotting Indicated in the alkaline hematin data during the last 56 days of treatment.
Time frame: The last 56 days of treatment (approximately days 33 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants including participants with less than 56 days of treatment who bled but excluded those who did not bleed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 66 percentage of participants |
| Cohort 4 Elagolix 400 mg QD | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 60 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 45 percentage of participants |
| Cohort 4 Elagolix 100 mg BID | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 31 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 0 percentage of participants |
| Cohort 4 Placebo | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 0 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 66 percentage of participants |
| Cohort 1 Elagolix 200 mg BID | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 44 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 0 percentage of participants |
| Cohort 1 Placebo | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 0 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 19 percentage of participants |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 31 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 73 percentage of participants |
| Cohort 5 Elagolix 600 mg QD | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 77 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 79 percentage of participants |
| Cohort 2 Elagolix 300 mg BID | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 66 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 0 percentage of participants |
| Cohort 2 Placebo | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 0 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Suppression of bleeding | 32 percentage of participants |
| Cohort 6 Elagolix 300 mg BID + CEP | Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment | Amenorrhea | 19 percentage of participants |
Secondary
Percent Change From Baseline to Month 3 in Uterine Volume
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time frame: Baseline and month 3
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available uterine volume data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percent Change From Baseline to Month 3 in Uterine Volume | -21.01 percent change | Standard Deviation 26.79 |
| Cohort 4 Elagolix 100 mg BID | Percent Change From Baseline to Month 3 in Uterine Volume | -21.37 percent change | Standard Deviation 24.84 |
| Cohort 4 Placebo | Percent Change From Baseline to Month 3 in Uterine Volume | 18.72 percent change | Standard Deviation 15.59 |
| Cohort 1 Elagolix 200 mg BID | Percent Change From Baseline to Month 3 in Uterine Volume | -21.68 percent change | Standard Deviation 29.8 |
| Cohort 1 Placebo | Percent Change From Baseline to Month 3 in Uterine Volume | -8.62 percent change | Standard Deviation 20.58 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percent Change From Baseline to Month 3 in Uterine Volume | -17.43 percent change | Standard Deviation 19.51 |
| Cohort 5 Elagolix 600 mg QD | Percent Change From Baseline to Month 3 in Uterine Volume | -27.99 percent change | Standard Deviation 23.34 |
| Cohort 2 Elagolix 300 mg BID | Percent Change From Baseline to Month 3 in Uterine Volume | -33.25 percent change | Standard Deviation 16.55 |
| Cohort 2 Placebo | Percent Change From Baseline to Month 3 in Uterine Volume | -1.92 percent change | Standard Deviation 17.52 |
| Cohort 6 Elagolix 300 mg BID + CEP | Percent Change From Baseline to Month 3 in Uterine Volume | -10.06 percent change | Standard Deviation 30.93 |
p-value: <0.001Kruskal-Wallis
p-value: <0.001Kruskal-Wallis
p-value: 0.052Kruskal-Wallis
p-value: <0.001Kruskal-Wallis
Secondary
Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Time frame: Baseline and month 3
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants with available fibroid volume data at baseline and month 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | 14.23 percent change | Standard Deviation 187.83 |
| Cohort 4 Elagolix 100 mg BID | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -22.19 percent change | Standard Deviation 51.14 |
| Cohort 4 Placebo | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -7.26 percent change | Standard Deviation 36.35 |
| Cohort 1 Elagolix 200 mg BID | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -38.52 percent change | Standard Deviation 41.72 |
| Cohort 1 Placebo | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -2.05 percent change | Standard Deviation 71.83 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -25.77 percent change | Standard Deviation 46.64 |
| Cohort 5 Elagolix 600 mg QD | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -16.60 percent change | Standard Deviation 39.61 |
| Cohort 2 Elagolix 300 mg BID | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -35.79 percent change | Standard Deviation 24.49 |
| Cohort 2 Placebo | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | 6.70 percent change | Standard Deviation 45.42 |
| Cohort 6 Elagolix 300 mg BID + CEP | Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid | -4.94 percent change | Standard Deviation 100.68 |
p-value: 0.072Kruskal-Wallis
p-value: 0.161Kruskal-Wallis
p-value: 0.173Kruskal-Wallis
p-value: 0.003Kruskal-Wallis
Secondary
Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment. Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Time frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Population: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. Last observation carried forward (LOCF) imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the electronic diary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 4 Elagolix 400 mg QD | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -83.83 percent change | Standard Deviation 35.23 |
| Cohort 4 Elagolix 100 mg BID | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -71.85 percent change | Standard Deviation 49.2 |
| Cohort 4 Placebo | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -6.98 percent change | Standard Deviation 40.78 |
| Cohort 1 Elagolix 200 mg BID | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -81.03 percent change | Standard Deviation 55.77 |
| Cohort 1 Placebo | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -11.12 percent change | Standard Deviation 103.11 |
| Cohort 3 Elagolix 200 mg BID + LD E2/NETA | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -79.60 percent change | Standard Deviation 43.63 |
| Cohort 5 Elagolix 600 mg QD | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -88.58 percent change | Standard Deviation 39.58 |
| Cohort 2 Elagolix 300 mg BID | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -97.31 percent change | Standard Deviation 12.57 |
| Cohort 2 Placebo | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -42.64 percent change | Standard Deviation 39.68 |
| Cohort 6 Elagolix 300 mg BID + CEP | Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) | -85.39 percent change | Standard Deviation 28.08 |
p-value: 0.00595% CI: [-113.39, -21.96]ANCOVA
p-value: <0.00195% CI: [-102.93, -48.28]ANCOVA
p-value: <0.00195% CI: [-91.14, -37.39]ANCOVA
p-value: <0.00195% CI: [-73.24, -40.45]ANCOVA