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

• ClinicalTrials.gov Identifier: NCT01817530
• Recruitment Status: Completed
• First Posted: March 25, 2013
• Results First Posted: July 21, 2020
• Last Update Posted: July 21, 2020
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Heavy Uterine Bleeding; Uterine Fibroids	Other: Elagolix placebo; Drug: Elagolix; Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate; Drug: 1 mg estradiol / 0.5 mg norethindrone acetate; Drug: E2/NETA placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 571 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids
• Actual Study Start Date: April 8, 2013
• Actual Primary Completion Date: June 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Cohort 1: Placebo; Placebo for elagolix and placebo for E2/NETA twice daily (BID)	Other: Elagolix placebo; oral coated tablet; Drug: E2/NETA placebo; oral hard capsule
Experimental: Cohort 1: Elagolix 300 mg BID; Elagolix 300 mg BID alone	Drug: Elagolix; oral coated tablet; Other Name: ABT-620; Drug: E2/NETA placebo; oral hard capsule
Experimental: Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD; Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)	Drug: Elagolix; oral coated tablet; Other Name: ABT-620; Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate; oral hard capsule; Other Name: Activelle, Activella, low dose (LD) E2/NETA
Experimental: Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD; Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD	Drug: Elagolix; oral coated tablet; Other Name: ABT-620; Drug: 1 mg estradiol / 0.5 mg norethindrone acetate; oral hard capsule; Other Names: Activelle; Activella; standard dose (SD) E2/NETA
Placebo Comparator: Cohort 2: Placebo; Placebo for elagolix and E2/NETA QD	Other: Elagolix placebo; oral coated tablet; Drug: E2/NETA placebo; oral hard capsule
Experimental: Cohort 2: Elagolix 600 mg QD; Elagolix 600 mg QD alone	Drug: Elagolix; oral coated tablet; Other Name: ABT-620; Drug: E2/NETA placebo; oral hard capsule
Experimental: Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD; Elagolix 600 mg QD plus LD E2/NETA QD	Drug: Elagolix; oral coated tablet; Other Name: ABT-620; Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate; oral hard capsule; Other Name: Activelle, Activella, low dose (LD) E2/NETA
Experimental: Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD; Elagolix 600 mg QD plus SD E2/NETA QD	Drug: Elagolix; oral coated tablet; Other Name: ABT-620; Drug: 1 mg estradiol / 0.5 mg norethindrone acetate; oral hard capsule; Other Names: Activelle; Activella; standard dose (SD) E2/NETA

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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 :

1. 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 [ Time Frame: 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.
2. 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 [ Time Frame: 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.
3. Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month [ Time Frame: 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.
4. Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month [ Time Frame: 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.
5. Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment [ Time Frame: 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.
6. Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment [ Time Frame: 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.
7. Mean Change in the Number of Bleeding Days From Baseline to Month 6 [ Time Frame: 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.
8. Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6 [ Time Frame: 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.
9. Change in Bleeding Severity Scores From Baseline at the Final Month [ Time Frame: 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.
10. Mean Change in Hemoglobin Concentration From Baseline to Final Visit [ Time Frame: 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.
11. Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit [ Time Frame: 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.
12. Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit [ Time Frame: 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.
13. Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit [ Time Frame: 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.
14. Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit [ Time Frame: 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.
15. Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit [ Time Frame: 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.
16. Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit [ Time Frame: 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.
17. Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire [ 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 ]
    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.
18. Percentage of Participants Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids [ Time Frame: Month 6 ]
    The percentage of participants who successfully avoided surgical or invasive procedures for Uterine Fibroids was assessed.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 51 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: Charlotte Owens, MD; AbbVie

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Carr BR, Stewart EA, Archer DF, Al-Hendy A, Bradley L, Watts NB, Diamond MP, Gao J, Owens CD, Chwalisz K, Duan WR, Soliman AM, Dufek MB, Simon JA. Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2018 Nov;132(5):1252-1264. doi: 10.1097/AOG.0000000000002933.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT01817530
• Other Study ID Numbers: M12-813; 2013-000082-37 ( EudraCT Number )
• First Posted: March 25, 2013
• Results First Posted: July 21, 2020
• Last Update Posted: July 21, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

Keywords provided by AbbVie:

Uterine Fibroids; Leiomyomata; Elagolix; Menorrhagia; Elagolix sodium; Heavy Uterine Bleeding; ABT-620

Additional relevant MeSH terms:

Leiomyoma; Myofibroma; Uterine Hemorrhage; Menorrhagia; Hemorrhage; Pathologic Processes; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Connective Tissue Diseases; Uterine Diseases; Menstruation Disturbances; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Norethindrone; Norethindrone Acetate; Estradiol; Polyestradiol phosphate; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Contraceptives, Oral