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Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01441635
Recruitment Status : Completed
First Posted : September 28, 2011
Results First Posted : July 15, 2020
Last Update Posted : July 15, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

Brief Summary:
The purpose of this proof-of-concept study is to assess the safety and effectiveness of elagolix versus placebo to reduce uterine bleeding associated with uterine fibroids, and to reduce fibroid volume and uterine volume in premenopausal women 20 to 49 years of age with heavy uterine bleeding.

Condition or disease Intervention/treatment Phase
Heavy Uterine Bleeding Uterine Fibroids Drug: Elagolix Drug: Placebo Drug: Estradiol/Norethindrone acetate (E2/NETA) Drug: Estradiol Drug: Progesterone Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 271 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2a Proof Of Concept Study to Evaluate the Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids
Actual Study Start Date : September 8, 2011
Actual Primary Completion Date : November 2013
Actual Study Completion Date : May 17, 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Elagolix

Arm Intervention/treatment
Experimental: Cohort 4 Elagolix 400 mg QD
Participants received elagolix 400 mg once a day (QD) for 3 months.
Drug: Elagolix
Elagolix tablets
Other Name: ABT-620

Experimental: Cohort 4 Elagolix 100 mg BID
Participants received elagolix 100 mg twice a day (BID) for 3 months.
Drug: Elagolix
Elagolix tablets
Other Name: ABT-620

Placebo Comparator: Cohort 4 Placebo
Participants received placebo to elagolix BID for 3 months.
Drug: Placebo
Matching placebo tablets

Experimental: Cohort 1 Elagolix 200 mg BID
Participants received elagolix 200 mg twice a day for 3 months.
Drug: Elagolix
Elagolix tablets
Other Name: ABT-620

Placebo Comparator: Cohort 1 Placebo
Participants received placebo to elagolix twice a day for 3 months.
Drug: Placebo
Matching placebo tablets

Placebo Comparator: Cohort 3 Elagolix 200 mg BID + LD E2/NETA
Participants received elagolix 200 mg twice a day plus continuous low-dose (LD) estradiol (E2) 0.5 mg/norethindrone acetate 0.1 mg (NETA) once a day for 3 months.
Drug: Elagolix
Elagolix tablets
Other Name: ABT-620

Drug: Estradiol/Norethindrone acetate (E2/NETA)
A continuous once-daily oral tablet containing estrogen and progestin; the low-dose strength contains estradiol 0.5 mg and norethindrone acetate 0.1 mg.
Other Name: Activella®

Experimental: Cohort 5 Elagolix 600 mg QD
Participants received elagolix 600 mg once a day for 3 months.
Drug: Elagolix
Elagolix tablets
Other Name: ABT-620

Experimental: Cohort 2 Elagolix 300 mg BID
Participants received elagolix 300 mg twice a day for 3 months.
Drug: Elagolix
Elagolix tablets
Other Name: ABT-620

Experimental: Cohort 2 Placebo
Participants received placebo to elagolix BID for 3 months.
Drug: Placebo
Matching placebo tablets

Experimental: Cohort 6 Elagolix 300 mg BID + CEP
Participants received elagolix 300 mg twice a day plus cyclical estrogen/progesterone (CEP, consisting of estradiol 1 mg a day and progesterone 200 mg on days 17 to 28 of each 30-day treatment cycle) for 3 months.
Drug: Elagolix
Elagolix tablets
Other Name: ABT-620

Drug: Estradiol
1.0 mg micronized estradiol tablets administered once a day
Other Name: Estrace®

Drug: Progesterone
Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle
Other Name: Prometrium®




Primary Outcome Measures :
  1. Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) [ Time Frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) ]

    The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

    Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.



Secondary Outcome Measures :
  1. Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL) [ Time Frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) ]

    The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

    Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.


  2. Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment [ Time Frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) ]

    The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

    Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.


  3. Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment [ Time Frame: The last 28 days of treatment (approximately days 61 to 90) ]

    The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

    Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.


  4. Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment [ Time Frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90) ]

    The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.

    Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.


  5. Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3 [ Time Frame: Baseline and Month 3 ]

    The percentage of subjects with changes in hemoglobin concentration from Baseline to Month 3 in each of the following categories:

    • No change from baseline in hemoglobin
    • Decrease from baseline in hemoglobin ≥ -0.5 g/dL
    • Decrease from baseline in hemoglobin ≥ -1.0 g/dL
    • Increase from baseline in hemoglobin ≥ 0.5 g/dL
    • Increase from baseline in hemoglobin ≥ 1.0 g/dL

    The above categories are not all mutually exclusive or exhaustive.


  6. Change in Hemoglobin Concentration From Baseline to Month 3 [ Time Frame: Baseline and Month 3 ]
  7. Change From Baseline to Month 3 in Uterine Bleeding Score [ Time Frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90) ]

    Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

    • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
    • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
    • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
    • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
    • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
    • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

  8. Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding [ Time Frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90) ]

    Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

    • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
    • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
    • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
    • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
    • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
    • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

    A day with any uterine bleeding is defined as a days with a bleeding score ≥ 1.


  9. Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding [ Time Frame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90) ]

    Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

    • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
    • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
    • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
    • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
    • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
    • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

    A day with moderate to very heavy bleeding is defined as a days with a bleeding score ≥ 3.


  10. Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3 [ Time Frame: Month 3 (average bleeding score over days 61 to 90) ]

    Participants recorded the previous days' presence and severity of bleeding every morning in an eDiary according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:

    • 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
    • 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
    • 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
    • 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
    • 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
    • 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.

    Any bleeding is defined as a score ≥ 1 and moderate to very heavy bleeding is defined as a score ≥ 3.


  11. Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment [ Time Frame: The last 56 days of treatment (approximately days 33 to 90) ]

    Suppression of bleeding is defined as no record of bleeding (spotting allowed) in the e-diary and no record of bleeding Indicated in the alkaline hematin data during the last 56 days of treatment.

    Amenorrhea is defined as no record of bleeding or spotting indicated in the e-diary and no record of bleeding or spotting Indicated in the alkaline hematin data during the last 56 days of treatment.


  12. Percent Change From Baseline to Month 3 in Uterine Volume [ Time Frame: Baseline and month 3 ]
    Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.

  13. Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit [ Time Frame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued. ]
    Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.

  14. Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid [ Time Frame: Baseline and month 3 ]
    The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.

  15. Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit [ Time Frame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued. ]
    The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.

  16. Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL) [ Time Frame: Baseline and month 3 ]

    The UFS-QoL is a disease-specific, self-administered, validated questionnaire developed to evaluate the symptoms associated with uterine fibroids and their impact on health-related quality of life (HRQL) in women with symptomatic uterine fibroids. The questionnaire consists of 37 questions, divided into 2 parts: 1) an 8-item symptom severity scale and 2) a 29-item HRQL subscale comprising 6 domains (concern, activities, energy/mood, control, self-consiousness, and sexual function), with a 4-week recall. All items are scored on a 5-point scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores were summed and transformed into a 0 to 100 point scale to provide a total score for each of the 2 components.

    Lower symptom severity scores indicate better quality of life and higher total HRQL scores indicate better quality of life.


  17. Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores [ Time Frame: Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90) ]
    The uterine fibroid daily symptom scale is self-administered questionnaire, with a scale that ranges from 0 to 10 for the symptoms of pelvic pain, fatigue, and cramping and the impact of uterine fibroids on the subject's daily life, with 0 being the absence of the symptom and 10 being the worst severity of the symptoms or completely preventing the subjects from performing daily activities. Participants self-reported values daily in the e-Diary.

  18. Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0 [ Time Frame: Baseline and month 3 ]

    The Subject Intention Questionnaire (SSIQ) is a non-validated, exploratory questionnaires intended to evaluate the subject's intent to undergo surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to consider surgery) to 10 (very likely to consider surgery).

    SSIQ included the 2 following questions:

    1. How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now?
    2. How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?

  19. Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0 [ Time Frame: Baseline and month 3 ]

    The Physician Intention Questionnaire (PSIQ) is a non-validated, exploratory questionnaire intended to evaluate the investigator's intent to recommend surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to recommend surgery) to 10 (very likely to recommend surgery).

    The PSIQ included the 2 following questions:

    1. How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now?
    2. How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject is a pre-menopausal female 20 to 49 years of age.
  • Subject has a diagnosis of uterine fibroids documented by a pelvic ultrasound assessed by a central reader and verification that a fibroid present met the following criteria:

    • At least 1 fibroid with diameter ≥ 2 cm (longest diameter), or multiple small fibroids with a total uterine volume of ≥ 200 cm³ to ≤ 2,500 cm³ (approximately 22 weeks' gestation) as documented by a centrally read ultrasound.
    • Only intramural, submucosal non-pedunculated, and subserosal fibroids qualified subjects for enrollment (intracavitary pedunculated fibroids were exclusionary).
    • Ultrasound procedures were performed during the Screening Period, and subjects were not randomized until the investigator reviewed the central reader results verifying the inclusion requirements.
  • Subject has a history of regular menstrual cycles between 24 to 35 days.
  • Subject has heavy uterine bleeding associated with uterine fibroids as evidenced by blood loss > 80 mL during 2 screening menstrual cycles, measured by the alkaline hematin method.

Exclusion Criteria:

  • Subject has had a myomectomy, uterine artery embolization, or high intensity focused ultrasound for fibroid destruction within 1 year prior to randomization or any history of endometrial ablation.
  • Subject has a history of osteoporosis or other metabolic bone disease.
  • Subject shows evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including depression), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes.
  • Subject has a history of clinically significant condition(s) including but not limited to:

    • Endometriosis
    • Epilepsy or seizures
    • Type 1 diabetes
    • Any cancer (except basal cell carcinoma of the skin), including breast or ovarian cancer or subject has taken any systemic cancer chemotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01441635


Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
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Study Director: AbbVie Inc. AbbVie
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT01441635    
Other Study ID Numbers: M12-663
First Posted: September 28, 2011    Key Record Dates
Results First Posted: July 15, 2020
Last Update Posted: July 15, 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):
Uterine Fibroids
Heavy Uterine Bleeding
Elagolix
Menorrhagia
ABT-620
Leiomyomata
Elagolix sodium
Additional relevant MeSH terms:
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Leiomyoma
Myofibroma
Uterine Hemorrhage
Hemorrhage
Pathologic Processes
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Connective Tissue Diseases
Uterine Diseases
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Norethindrone
Norethindrone Acetate
Estradiol
Polyestradiol phosphate
Progesterone
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins
Contraceptives, Oral, Synthetic
Contraceptives, Oral