Safety and Efficacy in Premenopausal Women With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF)

Phase 2

Completed

• Conditions: Heavy Uterine Bleeding; Uterine Fibroids
• Interventions: Other: Elagolix placebo; Drug: Elagolix; Drug: E2/NETA placebo; Drug: 1 mg estradiol / 0.5 mg norethindrone acetate; Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate

• Registration Number: NCT01817530
• Lead Sponsor: AbbVie

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-03-21
• Study First Submitted QC: 2013-03-21
• Study First Posted: 2013-03-25
• Study Start: 2013-04-08
• Primary Completion: 2015-06
• Study Completion: 2015-12
• Disposition First Submitted: 2016-06-15
• Disposition First Submitted QC: 2016-06-15
• Disposition First Posted: 2016-06-16
• Status Verified: 2020-06
• Results First Submitted: 2020-06-09
• Results First Submitted QC: 2020-07-07
• Last Update Submitted: 2020-07-07
• Results First Posted: 2020-07-21
• Last Update Posted: 2020-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 571

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: Placebo	Elagolix placebo	Placebo for elagolix and placebo for E2/NETA twice daily (BID)
Cohort 1: Placebo	E2/NETA placebo	Placebo for elagolix and placebo for E2/NETA twice daily (BID)
Cohort 1: Elagolix 300 mg BID	Elagolix	Elagolix 300 mg BID alone
Cohort 1: Elagolix 300 mg BID	E2/NETA placebo	Elagolix 300 mg BID alone
Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD	Elagolix	Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)
Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD	Elagolix	Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD
Cohort 2: Placebo	Elagolix placebo	Placebo for elagolix and E2/NETA QD
Cohort 2: Placebo	E2/NETA placebo	Placebo for elagolix and E2/NETA QD
Cohort 2: Elagolix 600 mg QD	E2/NETA placebo	Elagolix 600 mg QD alone
Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD	Elagolix	Elagolix 600 mg QD plus SD E2/NETA QD
Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD	1 mg estradiol / 0.5 mg norethindrone acetate	Elagolix 600 mg QD plus SD E2/NETA QD
Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD	1 mg estradiol / 0.5 mg norethindrone acetate	Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD
Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD	0.5 mg estradiol / 0.1 mg norethindrone acetate	Elagolix 600 mg QD plus LD E2/NETA QD
Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD	0.5 mg estradiol / 0.1 mg norethindrone acetate	Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)
Cohort 2: Elagolix 600 mg QD	Elagolix	Elagolix 600 mg QD alone
Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD	Elagolix	Elagolix 600 mg QD plus LD E2/NETA QD

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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 ≥ 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.
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.
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.
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.
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.
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.
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.
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.