Heavy Uterine Bleeding, Uterine Fibroids
Conditions
Keywords
Uterine Fibroids, Leiomyomata, Elagolix, Menorrhagia, Elagolix sodium, Heavy Uterine Bleeding, ABT-620
Brief summary
This is a Phase 2b randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of elagolix alone and in combination with add-back therapy versus placebo on heavy menstrual bleeding in premenopausal women 18 to 51 years of age with uterine fibroids.
Interventions
OTHERElagolix placebo
oral coated tablet
DRUGElagolix
oral coated tablet
DRUG0.5 mg estradiol / 0.1 mg norethindrone acetate
oral hard capsule
DRUG1 mg estradiol / 0.5 mg norethindrone acetate
oral hard capsule
DRUGE2/NETA placebo
oral hard capsule
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 51 Years
Healthy volunteers
No
Inclusion criteria
* Subject is pre-menopausal female 18 to 51 years of age at Screening. * Subject has diagnosis of uterine fibroids documented by a Pelvic Ultrasound. * Subject has heavy uterine bleeding associated with uterine fibroids.
Exclusion criteria
* Subject has had a myomectomy, uterine artery embolization or high intensity focused ultrasound for fibroid destruction within 6 months prior to Screening or endometrial ablation within 5 years prior to Screening. * 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, schizophrenia, bipolar disorder), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes. Subject has any history of attempted suicide. * Subject has a history of clinically significant condition(s) including but not limited to: \* Symptomatic Endometriosis \* Epilepsy or seizures \* Type 1 diabetes \* Chronic kidney disease \* Any cancer (except treated 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 |
|---|---|---|
| Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | Baseline, Final Month (last 28 days of treatment) | The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of \< 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | Baseline, third last 28 days of treatment (last 84 to 57 days of treatment) | The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume \< 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period. |
| Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | Final Month (last 28 days of treatment) | Percentage of participants who achieved an MBL volume of \< 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. |
| Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | Baseline, Final Month (last 28 days of treatment) | Percentage of participants with a \>= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period. |
| Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | Last 56 days of treatment (after 10 days from first dose date) | Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment. |
| Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | Last 56 days of treatment (after 10 days from first dose date) | Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment. |
| Mean Change in the Number of Bleeding Days From Baseline to Month 6 | Baseline, Month 6 | The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug. |
| Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | Baseline, Month 6 | The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug. |
| Change in Bleeding Severity Scores From Baseline at the Final Month | Baseline, Final Month (last 28 days of treatment) | The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug. |
| Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | Baseline, second last 28 days of treatment (last 56 to 29 days of treatment) | The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume \< 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period. |
| Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination) | Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound. |
| Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination) | Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound. |
| Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination) | Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound. |
| Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination) | Total fibroid volume (3 largest fibroids) was measured by transvaginal ultrasound, or transabdominal ultrasound. |
| Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination) | Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound. |
| Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination) | Uterine volume was measured by transvaginal ultrasound or transabdominal ultrasound. |
| Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Baseline, Days 1-28, Days 29-56, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168 | The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug. Final Month is defined as the last 28 days prior to and including the last dose date of study drug. |
| Percentage of Participants Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids | Month 6 | The percentage of participants who successfully avoided surgical or invasive procedures for Uterine Fibroids was assessed. |
| Mean Change in Hemoglobin Concentration From Baseline to Final Visit | Baseline, Final Visit during treatment period (Month 6 or early termination) | Baseline is defined as the last measurement prior to the first dose of study drug. |
Participant flow
Recruitment details
Overall, 571 female participants were enrolled into the study across 86 sites (5 sites in the UK, 4 in Chile, 2 in Canada, 4 in Puerto Rico, and 71 in the US).
Pre-assignment details
Four participants were randomized in error; they were not dosed and were excluded from all analyses including demographic summaries.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Placebo Placebo for elagolix BID and placebo for E2/NETA QD | 65 |
| Cohort 1: Elagolix 300 mg BID Elagolix 300 mg BID and placebo for E2/NETA QD | 65 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD Elagolix 300 mg BID plus LD E2/NETA QD | 64 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD Elagolix 300 mg BID plus SD E2/NETA QD | 65 |
| Cohort 2: Placebo Placebo for elagolix QD and placebo for E2/NETA QD | 78 |
| Cohort 2: Elagolix 600 mg QD Elagolix 600 mg QD and placebo for E2/NETA QD | 77 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD Elagolix 600 mg QD plus LD E2/NETA QD | 76 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD Elagolix 600 mg QD plus SD E2/NETA QD | 77 |
| Total | 567 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 | 2 | 5 | 0 | 10 | 5 | 8 |
| Overall Study | Consent Withdrawn by Subject | 3 | 4 | 7 | 3 | 5 | 3 | 3 | 10 |
| Overall Study | Exclusionary Medication Received | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 4 | 2 | 1 | 3 | 2 | 8 | 4 |
| Overall Study | Other | 0 | 1 | 0 | 0 | 1 | 0 | 5 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Subject Noncompliant | 3 | 1 | 0 | 4 | 0 | 1 | 1 | 1 |
| Overall Study | Surgery or Invasive Intervention | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Placebo | Cohort 1: Elagolix 300 mg BID | Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Cohort 2: Placebo | Cohort 2: Elagolix 600 mg QD | Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.5 years STANDARD_DEVIATION 6.14 | 42.0 years STANDARD_DEVIATION 4.76 | 43.0 years STANDARD_DEVIATION 5.02 | 43.8 years STANDARD_DEVIATION 4.66 | 42.3 years STANDARD_DEVIATION 4.78 | 42.1 years STANDARD_DEVIATION 4.93 | 41.1 years STANDARD_DEVIATION 5.74 | 42.2 years STANDARD_DEVIATION 5.4 | 42.3 years STANDARD_DEVIATION 5.22 |
| Sex: Female, Male Female | 65 Participants | 65 Participants | 64 Participants | 65 Participants | 78 Participants | 77 Participants | 76 Participants | 77 Participants | 567 Participants |
| Sex: Female, Male Male | 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 65 | 0 / 64 | 0 / 65 | 0 / 78 | 0 / 77 | 0 / 76 | 0 / 77 |
| other Total, other adverse events | 33 / 65 | 45 / 65 | 37 / 64 | 44 / 65 | 42 / 78 | 59 / 77 | 43 / 76 | 51 / 77 |
| serious Total, serious adverse events | 6 / 65 | 3 / 65 | 3 / 64 | 1 / 65 | 1 / 78 | 5 / 77 | 3 / 76 | 4 / 77 |
Outcome results
Primary
Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month
The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of \< 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.
Time frame: Baseline, Final Month (last 28 days of treatment)
Population: Modified Intent-to-Treat (ITT): randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with \< 28 days of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 26.56 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 91.94 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 85.25 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 79.03 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 31.58 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 90.14 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 72.6 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 81.58 percentage of participants |
p-value: <0.00195% CI: [11.12, 95.05]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [6.72, 41.3]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [4.79, 25.84]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [7.81, 49.27]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [2.95, 12.3]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [4.79, 22.34]Regression, Logistic
p-value: <0.001Chi-squared
Secondary
Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire
The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug. Final Month is defined as the last 28 days prior to and including the last dose date of study drug.
Time frame: Baseline, Days 1-28, Days 29-56, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -7.0 units on a scale | Standard Error 10.74 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -5.6 units on a scale | Standard Error 13.39 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -5.4 units on a scale | Standard Error 17.08 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | -5.7 units on a scale | Standard Error 15.83 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | 7.5 units on a scale | Standard Error 27.75 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -5.3 units on a scale | Standard Error 13.19 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -6.8 units on a scale | Standard Error 14.28 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | -3.3 units on a scale | Standard Error 10.11 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | -4.1 units on a scale | Standard Error 13.16 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | -5.6 units on a scale | Standard Error 10.94 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | -4.4 units on a scale | Standard Error 17.82 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -4.5 units on a scale | Standard Error 13.12 |
| Cohort 1: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | 3.4 units on a scale | Standard Error 27.8 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -5.2 units on a scale | Standard Error 12.13 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | -3.4 units on a scale | Standard Error 8.21 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | -8.0 units on a scale | Standard Error 1.42 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | -6.4 units on a scale | Standard Error 12.99 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -7.8 units on a scale | Standard Error 11.75 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | -4.1 units on a scale | Standard Error 13.1 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -6.7 units on a scale | Standard Error 11.94 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | -7.2 units on a scale | Standard Error 11.04 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | -3.1 units on a scale | Standard Error 2.15 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -4.0 units on a scale | Standard Error 14.11 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -8.0 units on a scale | Standard Error 12.65 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | -7.6 units on a scale | Standard Error 12.03 |
| Cohort 1: Elagolix 300 mg BID | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -5.8 units on a scale | Standard Error 8.78 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | -3.1 units on a scale | Standard Error 7.88 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | -4.1 units on a scale | Standard Error 8.4 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -4.1 units on a scale | Standard Error 10.15 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -2.1 units on a scale | Standard Error 10.91 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | 4.1 units on a scale | — |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -4.4 units on a scale | Standard Error 6.59 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -5.2 units on a scale | Standard Error 9.05 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | -5.3 units on a scale | Standard Error 9.43 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -5.1 units on a scale | Standard Error 9.94 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -3.8 units on a scale | Standard Error 10.37 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | -1.0 units on a scale | Standard Error 11.57 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | -4.8 units on a scale | Standard Error 10.33 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | 1.3 units on a scale | — |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -3.3 units on a scale | Standard Error 13.01 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | -3.3 units on a scale | — |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | -1.4 units on a scale | Standard Error 6.42 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -1.1 units on a scale | Standard Error 10.5 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -3.0 units on a scale | Standard Error 10.69 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -3.7 units on a scale | Standard Error 10.76 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | 0.0 units on a scale | Standard Error 9.89 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | 1.4 units on a scale | Standard Error 1.75 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | -3.2 units on a scale | Standard Error 11.26 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -3.5 units on a scale | Standard Error 12.59 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | 0.7 units on a scale | Standard Error 6.59 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -2.9 units on a scale | Standard Error 9.44 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | -3.4 units on a scale | Standard Error 12.1 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | -10.5 units on a scale | — |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | 0.1 units on a scale | Standard Error 11.92 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -0.5 units on a scale | Standard Error 13.08 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | -0.2 units on a scale | Standard Error 12.49 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -0.4 units on a scale | Standard Error 10.46 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -0.3 units on a scale | Standard Error 7.13 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | 0.4 units on a scale | Standard Error 4.71 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | -6.2 units on a scale | Standard Error 1.51 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | -2.7 units on a scale | Standard Error 7.15 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | 0.1 units on a scale | Standard Error 7.34 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -0.8 units on a scale | Standard Error 12.46 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -0.2 units on a scale | Standard Error 7.47 |
| Cohort 2: Placebo | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -0.8 units on a scale | Standard Error 11.34 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -2.0 units on a scale | Standard Error 9.79 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | -2.7 units on a scale | Standard Error 7.27 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -4.2 units on a scale | Standard Error 7.72 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | -4.5 units on a scale | Standard Error 8.55 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -5.1 units on a scale | Standard Error 9.4 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | -17.3 units on a scale | Standard Error 26.2 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | -5.5 units on a scale | Standard Error 8.44 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | -2.4 units on a scale | Standard Error 14.37 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -4.0 units on a scale | Standard Error 9.4 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -3.8 units on a scale | Standard Error 10.53 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -5.9 units on a scale | Standard Error 9.45 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | -2.8 units on a scale | Standard Error 11.85 |
| Cohort 2: Elagolix 600 mg QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | -3.1 units on a scale | — |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | -2.1 units on a scale | Standard Error 4.44 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | -2.7 units on a scale | Standard Error 7.58 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -3.6 units on a scale | Standard Error 7.35 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | -2.2 units on a scale | Standard Error 6.22 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | -3.3 units on a scale | Standard Error 6.42 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -2.0 units on a scale | Standard Error 8.23 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -4.4 units on a scale | Standard Error 8.21 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -2.2 units on a scale | Standard Error 5.54 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | -3.0 units on a scale | Standard Error 7.48 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | -5.6 units on a scale | Standard Error 6.45 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -1.6 units on a scale | Standard Error 8.35 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | -4.0 units on a scale | Standard Error 8.13 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -3.3 units on a scale | Standard Error 8.09 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 113-140 | -5.3 units on a scale | Standard Error 8.99 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Final Month | -2.3 units on a scale | Standard Error 10.56 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 141-168 | -4.8 units on a scale | Standard Error 9.3 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 29-56 | -2.5 units on a scale | Standard Error 8.54 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 57-84 | -3.8 units on a scale | Standard Error 8.92 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 85-112 | -4.1 units on a scale | Standard Error 8.96 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 113-140 | -7.0 units on a scale | Standard Error 7.12 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 57-84 | -3.9 units on a scale | Standard Error 6.87 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 1-28 | -2.3 units on a scale | Standard Error 7.82 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 85-112 | -5.0 units on a scale | Standard Error 5.12 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | PT Days 141-168 | -6.4 units on a scale | Standard Error 5.94 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 29-56 | -2.3 units on a scale | Standard Error 9.31 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire | Days 1-28 | 0.0 units on a scale | Standard Error 6.26 |
Comparison: Final Monthp-value: 0.55695% CI: [-6.65, 3.59]ANCOVA
Comparison: Final Monthp-value: 0.67295% CI: [-6.33, 4.09]ANCOVA
Comparison: Final Monthp-value: 0.27495% CI: [-2.39, 8.36]ANCOVA
Comparison: Final Monthp-value: 0.22395% CI: [-5.26, 1.23]ANCOVA
Comparison: Final Monthp-value: 0.21595% CI: [-5.38, 1.22]ANCOVA
Comparison: Final Monthp-value: 0.39295% CI: [-4.75, 1.87]ANCOVA
Secondary
Change in Bleeding Severity Scores From Baseline at the Final Month
The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug.
Time frame: Baseline, Final Month (last 28 days of treatment)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and final month.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.3 units on a scale | Standard Error 0.08 |
| Cohort 1: Elagolix 300 mg BID | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.7 units on a scale | Standard Error 0.14 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.4 units on a scale | Standard Error 0.1 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.1 units on a scale | Standard Error 0.1 |
| Cohort 2: Placebo | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.2 units on a scale | Standard Error 0.08 |
| Cohort 2: Elagolix 600 mg QD | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.4 units on a scale | Standard Error 0.14 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.3 units on a scale | Standard Error 0.1 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Change in Bleeding Severity Scores From Baseline at the Final Month | -0.1 units on a scale | Standard Error 0.1 |
p-value: 0.00495% CI: [-0.79, -0.15]ANCOVA
p-value: 0.31495% CI: [-0.4, 0.13]ANCOVA
p-value: 0.30795% CI: [-0.12, 0.39]ANCOVA
p-value: 0.10695% CI: [-0.58, 0.06]ANCOVA
p-value: 0.42495% CI: [-0.36, 0.15]ANCOVA
p-value: 0.52895% CI: [-0.18, 0.35]ANCOVA
Secondary
Mean Change in Hemoglobin Concentration From Baseline to Final Visit
Baseline is defined as the last measurement prior to the first dose of study drug.
Time frame: Baseline, Final Visit during treatment period (Month 6 or early termination)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and final month.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 0.6 g/dL | Standard Error 0.17 |
| Cohort 1: Elagolix 300 mg BID | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 1.9 g/dL | Standard Error 0.17 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 1.9 g/dL | Standard Error 0.17 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 1.4 g/dL | Standard Error 0.17 |
| Cohort 2: Placebo | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 0.3 g/dL | Standard Error 0.15 |
| Cohort 2: Elagolix 600 mg QD | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 1.4 g/dL | Standard Error 0.16 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 1.1 g/dL | Standard Error 0.16 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Change in Hemoglobin Concentration From Baseline to Final Visit | 1.2 g/dL | Standard Error 0.16 |
p-value: <0.00195% CI: [0.8, 1.74]ANCOVA
p-value: <0.00195% CI: [0.78, 1.72]ANCOVA
p-value: <0.00195% CI: [0.33, 1.27]ANCOVA
p-value: <0.00195% CI: [0.65, 1.52]ANCOVA
p-value: <0.00195% CI: [0.29, 1.16]ANCOVA
p-value: <0.00195% CI: [0.4, 1.26]ANCOVA
Secondary
Mean Change in the Number of Bleeding Days From Baseline to Month 6
The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.
Time frame: Baseline, Month 6
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and Month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -1.2 days | Standard Error 0.63 |
| Cohort 1: Elagolix 300 mg BID | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -4.9 days | Standard Error 1.15 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -2.7 days | Standard Error 0.75 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -1.1 days | Standard Error 0.69 |
| Cohort 2: Placebo | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -1.4 days | Standard Error 0.49 |
| Cohort 2: Elagolix 600 mg QD | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -3.3 days | Standard Error 0.87 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -1.3 days | Standard Error 0.66 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Change in the Number of Bleeding Days From Baseline to Month 6 | -1.8 days | Standard Error 0.64 |
p-value: 0.00795% CI: [-6.28, -1.03]ANCOVA
p-value: 0.13295% CI: [-3.44, 0.46]ANCOVA
p-value: 0.87695% CI: [-1.71, 2]ANCOVA
p-value: 0.05595% CI: [-3.92, 0.04]ANCOVA
p-value: 0.89895% CI: [-1.52, 1.74]ANCOVA
p-value: 0.5995% CI: [-2.05, 1.17]ANCOVA
Secondary
Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6
The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.
Time frame: Baseline, Month 6
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and Month 6.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Placebo | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -1.0 days | Standard Error 0.15 |
| Cohort 1: Elagolix 300 mg BID | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -2.0 days | Standard Error 0.27 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -1.9 days | Standard Error 0.18 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -1.7 days | Standard Error 0.16 |
| Cohort 2: Placebo | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -0.7 days | Standard Error 0.14 |
| Cohort 2: Elagolix 600 mg QD | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -1.2 days | Standard Error 0.25 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -1.4 days | Standard Error 0.19 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 | -1.8 days | Standard Error 0.18 |
p-value: 0.00195% CI: [-1.64, -0.42]ANCOVA
p-value: <0.00195% CI: [-1.42, -0.48]ANCOVA
p-value: 0.00295% CI: [-1.12, -0.25]ANCOVA
p-value: 0.11895% CI: [-1.04, 0.12]ANCOVA
p-value: 0.00495% CI: [-1.16, -0.22]ANCOVA
p-value: <0.00195% CI: [-1.51, -0.59]ANCOVA
Secondary
Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit
Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound.
Time frame: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 9.0 percentage change | Standard Deviation 46.63 |
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 6.9 percentage change | Standard Deviation 35.31 |
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 13.2 percentage change | Standard Deviation 48.65 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -35.5 percentage change | Standard Deviation 26.32 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -35.6 percentage change | Standard Deviation 30.81 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -36.1 percentage change | Standard Deviation 30.59 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -19.6 percentage change | Standard Deviation 32.1 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -20.3 percentage change | Standard Deviation 33.54 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 20.0 percentage change | Standard Deviation 31.73 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 0.0 percentage change | Standard Deviation 47.07 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -3.7 percentage change | Standard Deviation 39.13 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -2.7 percentage change | Standard Deviation 46.63 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 6.7 percentage change | Standard Deviation 27.66 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 1.4 percentage change | Standard Deviation 30.03 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 3.0 percentage change | Standard Deviation 28.7 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -34.8 percentage change | Standard Deviation 30.36 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -33.5 percentage change | Standard Deviation 31.89 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -33.6 percentage change | Standard Deviation 23.74 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -12.8 percentage change | Standard Deviation 39.65 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -12.2 percentage change | Standard Deviation 40.59 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -17.2 percentage change | Standard Deviation 27.39 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -0.7 percentage change | Standard Deviation 42.98 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -1.9 percentage change | Standard Deviation 39.22 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 0.0 percentage change | Standard Deviation 40.17 |
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: 0.036Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
p-value: 0.04Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: 0.098Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: 0.014Kruskal-Wallis
Comparison: Month 6p-value: 0.409Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: 0.094Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: 0.002Kruskal-Wallis
Comparison: Final Visitp-value: 0.393Kruskal-Wallis
Secondary
Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit
Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound.
Time frame: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and final month.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 8.3 percentage change | Standard Deviation 50.97 |
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 4.6 percentage change | Standard Deviation 48.59 |
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 1.7 percentage change | Standard Deviation 33.61 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -41.9 percentage change | Standard Deviation 24.87 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -40.2 percentage change | Standard Deviation 27.6 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -39.6 percentage change | Standard Deviation 28.66 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -23.3 percentage change | Standard Deviation 30.34 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -24.0 percentage change | Standard Deviation 29.93 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -24.6 percentage change | Standard Deviation 27.58 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -12.9 percentage change | Standard Deviation 46.2 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -9.8 percentage change | Standard Deviation 40.31 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -8.8 percentage change | Standard Deviation 47.81 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -1.8 percentage change | Standard Deviation 30.1 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 5.4 percentage change | Standard Deviation 27.18 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 0.1 percentage change | Standard Deviation 28.82 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -34.4 percentage change | Standard Deviation 25.56 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -34.2 percentage change | Standard Deviation 31.14 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -36.4 percentage change | Standard Deviation 30.07 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -17.8 percentage change | Standard Deviation 30.49 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -17.5 percentage change | Standard Deviation 27.76 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -16.6 percentage change | Standard Deviation 32.65 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | -1.1 percentage change | Standard Deviation 46.66 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | -1.6 percentage change | Standard Deviation 42.75 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | -4.6 percentage change | Standard Deviation 39.97 |
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: 0.018Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: 0.021Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: 0.032Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: 0.007Kruskal-Wallis
Comparison: Month 6p-value: 0.495Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: 0.015Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: 0.002Kruskal-Wallis
Comparison: Final Visitp-value: 0.329Kruskal-Wallis
Secondary
Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit
Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound.
Time frame: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 17.5 percentage change | Standard Deviation 40.25 |
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 15.9 percentage change | Standard Deviation 38.06 |
| Cohort 1: Placebo | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 7.3 percentage change | Standard Deviation 25.12 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | -35.6 percentage change | Standard Deviation 25.74 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | -30.9 percentage change | Standard Deviation 28.87 |
| Cohort 1: Elagolix 300 mg BID | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | -31.5 percentage change | Standard Deviation 31.44 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | -21.9 percentage change | Standard Deviation 27.64 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | -19.4 percentage change | Standard Deviation 22.48 |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | -22.0 percentage change | Standard Deviation 28.52 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | -13.2 percentage change | Standard Deviation 23.86 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | -7.3 percentage change | Standard Deviation 20.7 |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | -11.8 percentage change | Standard Deviation 22.56 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 10.7 percentage change | Standard Deviation 20.73 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 8.4 percentage change | Standard Deviation 24.26 |
| Cohort 2: Placebo | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 11.6 percentage change | Standard Deviation 25.38 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | -24.7 percentage change | Standard Deviation 21.98 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | -26.00 percentage change | Standard Deviation 29.51 |
| Cohort 2: Elagolix 600 mg QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | -26.6 percentage change | Standard Deviation 28.26 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | -13.5 percentage change | Standard Deviation 25.09 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | -15.7 percentage change | Standard Deviation 21.84 |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | -11.5 percentage change | Standard Deviation 25.33 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | -6.7 percentage change | Standard Deviation 21.8 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | -6.1 percentage change | Standard Deviation 18.81 |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | -9.0 percentage change | Standard Deviation 22.12 |
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 3p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Month 6p-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Comparison: Final Visitp-value: <0.001Kruskal-Wallis
Secondary
Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment
Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment.
Time frame: Last 56 days of treatment (after 10 days from first dose date)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with \< 66 days of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 1.6 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 56.1 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 33.3 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 28.3 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 1.3 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 50.7 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 17.5 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment | 22.7 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month
Percentage of participants who achieved an MBL volume of \< 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.
Time frame: Final Month (last 28 days of treatment)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with \< 28 days of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 32.81 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 91.94 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 88.52 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 79.03 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 36.84 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 91.55 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 72.6 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month | 85.53 percentage of participants |
p-value: <0.00195% CI: [8.57, 71.32]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [6.57, 45.05]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [3.79, 19.92]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [7.11, 49.02]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [2.43, 10.04]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [5.17, 26.79]Regression, Logistic
p-value: <0.001Chi-squared
Secondary
Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment
Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment.
Time frame: Last 56 days of treatment (after 10 days from first dose date)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with \< 66 days of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 1.6 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 75.4 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 52.6 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 43.3 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 2.7 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 67.2 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 31.7 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment | 34.8 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids
The percentage of participants who successfully avoided surgical or invasive procedures for Uterine Fibroids was assessed.
Time frame: Month 6
Population: This endpoint was not completed due to lack of data collection.
Secondary
Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit
Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound.
Time frame: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 13.2 percentage of participants |
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 24.5 percentage of participants |
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 24.4 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 69.8 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 67.3 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 70.5 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 50.0 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 46.2 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 47.9 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 23.4 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 26.2 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 27.5 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 14.5 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 10.9 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 13.6 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 64.0 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 63.2 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 66.1 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 38.6 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 37.7 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 40.0 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 22.4 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 34.8 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 30.0 percentage of participants |
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: 0.188Regression, Logistic
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: 0.001Regression, Logistic
Comparison: Month 3p-value: 0.104Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: 0.021Regression, Logistic
Comparison: Month 6p-value: 0.859Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: 0.006Regression, Logistic
Comparison: Month 6p-value: 0.015Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: 0.007Regression, Logistic
Comparison: Final Visitp-value: 0.722Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: 0.032Regression, Logistic
Secondary
Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit
Total fibroid volume (3 largest fibroids) was measured by transvaginal ultrasound, or transabdominal ultrasound.
Time frame: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 13.2 percentage of participants |
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 24.4 percentage of participants |
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 24.5 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 75.0 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 73.6 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 79.6 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 57.4 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 50.0 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 54.2 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 41.2 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 31.9 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 40.5 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 18.2 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 16.7 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 9.4 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 62.0 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 64.4 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 66.7 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 40.0 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 34.0 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 40.9 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 3 | 22.4 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Month 6 | 34.8 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit | Final Visit | 30.0 percentage of participants |
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: 0.02Regression, Logistic
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: 0.002Regression, Logistic
Comparison: Month 3p-value: 0.061Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: 0.004Regression, Logistic
Comparison: Month 6p-value: 0.085Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: 0.012Regression, Logistic
Comparison: Month 6p-value: 0.049Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: 0.056Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: 0.005Regression, Logistic
Comparison: Final Visitp-value: 0.088Regression, Logistic
Secondary
Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit
Uterine volume was measured by transvaginal ultrasound or transabdominal ultrasound.
Time frame: Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Participants with an assessment at baseline and given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 3.4 percentage of participants |
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 2.0 percentage of participants |
| Cohort 1: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 5.2 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 78.7 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 73.1 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 73.2 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 58.0 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 42.9 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 58.9 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 18.5 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 26.8 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 31.9 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 1.4 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 1.4 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 1.6 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 57.1 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 63.1 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 62.5 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 29.3 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 32.7 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 36.8 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Final Visit | 23.4 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 3 | 17.5 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit | Month 6 | 26.0 percentage of participants |
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: 0.041Regression, Logistic
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: <0.001Regression, Logistic
Comparison: Month 3p-value: 0.008Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: 0.003Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: <0.001Regression, Logistic
Comparison: Month 6p-value: 0.003Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: 0.004Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: <0.001Regression, Logistic
Comparison: Final Visitp-value: 0.002Regression, Logistic
Secondary
Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month
Percentage of participants with a \>= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.
Time frame: Baseline, Final Month (last 28 days of treatment)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with \< 28 days of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 31.25 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 93.55 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 86.89 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 82.26 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 35.53 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 90.14 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 79.45 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month | 85.53 percentage of participants |
p-value: <0.00195% CI: [10.02, 98.83]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [5.77, 35.91]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [4.23, 22.8]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [6.66, 41.26]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [3.36, 14.68]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [4.85, 23.76]Regression, Logistic
p-value: <0.001Chi-squared
Secondary
Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment
The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume \< 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.
Time frame: Baseline, second last 28 days of treatment (last 56 to 29 days of treatment)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with \< 56 days of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 11.29 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 94.83 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 88.14 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 85.00 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 18.42 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 85.29 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 67.19 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment | 77.14 percentage of participants |
p-value: <0.00195% CI: [38.04, 641.22]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [21.1, 206.88]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [17.42, 156.09]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [10.45, 61.96]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [4.38, 21.25]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [7.13, 36.67]Regression, Logistic
p-value: <0.001Chi-squared
Secondary
Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment
The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume \< 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.
Time frame: Baseline, third last 28 days of treatment (last 84 to 57 days of treatment)
Population: Modified ITT: randomized participants who received at least 1 dose of randomized, double-blind study drug in this study. Excludes participants with \< 84 days of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Placebo | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 19.67 percentage of participants |
| Cohort 1: Elagolix 300 mg BID | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 96.43 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus LD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 89.47 percentage of participants |
| Cohort 1: Elagolix 300 mg BID Plus SD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 79.31 percentage of participants |
| Cohort 2: Placebo | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 21.62 percentage of participants |
| Cohort 2: Elagolix 600 mg QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 86.36 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus LD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 74.19 percentage of participants |
| Cohort 2: Elagolix 600 mg QD Plus SD E2/NETA QD | Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment | 72.31 percentage of participants |
p-value: <0.00195% CI: [25.93, 584.85]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [13.59, 121.03]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [7.44, 48.58]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [9.29, 55.77]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [4.88, 24.27]Regression, Logistic
p-value: <0.001Chi-squared
p-value: <0.00195% CI: [4.46, 21.22]Regression, Logistic
p-value: <0.001Chi-squared