Heavy Uterine BleedingPhase 2NCT01441635

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

A Phase 2 study testing Elagolix, Estradiol/Norethindrone acetate (E2/NETA) and Estradiol in people with Heavy Uterine Bleeding and Uterine Fibroids, run by AbbVie (prior sponsor, Abbott).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 20 to 49 years, women only
Conditions the study is for: Heavy Uterine Bleeding, Uterine Fibroids
What is being tested?: Elagolix, Estradiol/Norethindrone acetate (E2/NETA) and Estradiol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 271 participants
Where: No sites listed yet
Study dates: 8 Sep 2011to 17 May 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 49 years
Women only
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

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

About this study

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

Conditions: Heavy Uterine Bleeding, Uterine Fibroids
Being tested: Elagolix, Placebo, Estradiol/Norethindrone acetate (E2/NETA), Estradiol, Progesterone
Keywords: Uterine Fibroids, Heavy Uterine Bleeding, Elagolix, Menorrhagia, ABT-620, Leiomyomata, Elagolix sodium
Medical subject headings: Leiomyoma, Menorrhagia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ElagolixDrug
Also called ABT-620
Elagolix tablets
PlaceboDrug
Matching placebo tablets
Estradiol/Norethindrone acetate (E2/NETA)Drug
Also called Activella®
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.
EstradiolDrug
Also called Estrace®
1.0 mg micronized estradiol tablets administered once a day
ProgesteroneDrug
Also called Prometrium®
Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle

Study groups in NCT01441635
Study group	Role	What they receive
Cohort 4 Elagolix 400 mg QD	Experimental	Participants received elagolix 400 mg once a day (QD) for 3 months. Receives: Drug: Elagolix
Cohort 4 Elagolix 100 mg BID	Experimental	Participants received elagolix 100 mg twice a day (BID) for 3 months. Receives: Drug: Elagolix
Cohort 4 Placebo	Placebo comparator	Participants received placebo to elagolix BID for 3 months. Receives: Drug: Placebo
Cohort 1 Elagolix 200 mg BID	Experimental	Participants received elagolix 200 mg twice a day for 3 months. Receives: Drug: Elagolix
Cohort 1 Placebo	Placebo comparator	Participants received placebo to elagolix twice a day for 3 months. Receives: Drug: Placebo
Cohort 3 Elagolix 200 mg BID + LD E2/NETA	Placebo comparator	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. Receives: Drug: Elagolix; Drug: Estradiol/Norethindrone acetate (E2/NETA)
Cohort 5 Elagolix 600 mg QD	Experimental	Participants received elagolix 600 mg once a day for 3 months. Receives: Drug: Elagolix
Cohort 2 Elagolix 300 mg BID	Experimental	Participants received elagolix 300 mg twice a day for 3 months. Receives: Drug: Elagolix
Cohort 2 Placebo	Experimental	Participants received placebo to elagolix BID for 3 months. Receives: Drug: Placebo
Cohort 6 Elagolix 300 mg BID + CEP	Experimental	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. Receives: Drug: Elagolix; Drug: Estradiol; Drug: Progesterone

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.
Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Measured: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

Secondary outcomes (19)

Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.
Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Measured: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.
Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Measured: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.
Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Measured: The last 28 days of treatment (approximately days 61 to 90)
Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
The alkaline hematin method was used for the assessment of MBL. Sanitary products were collected at screening and for any spotting or bleeding episodes that occurred during treatment.
Participants with missing MBL volume for the last treatment period and no bleeding indicated in the electronic daily bleeding diary (eDiary) in the last treatment period, and participants with no post-baseline MBL data were assigned an MBL value of zero.
Measured: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3
The percentage of subjects with changes in hemoglobin concentration from Baseline to Month 3 in each of the following categories:
- No change from baseline in hemoglobin
- Decrease from baseline in hemoglobin ≥ -0.5 g/dL
- Decrease from baseline in hemoglobin ≥ -1.0 g/dL
- Increase from baseline in hemoglobin ≥ 0.5 g/dL
- Increase from baseline in hemoglobin ≥ 1.0 g/dL
The above categories are not all mutually exclusive or exhaustive.
Measured: Baseline and Month 3
Change in Hemoglobin Concentration From Baseline to Month 3
Measured: Baseline and Month 3
Change From Baseline to Month 3 in Uterine Bleeding Score
Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:
- 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
- 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
- 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
- 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
- 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
- 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.
Measured: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding
Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:
- 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
- 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
- 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
- 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
- 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
- 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.
A day with any uterine bleeding is defined as a days with a bleeding score ≥ 1.
Measured: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding
Participants recorded the previous days' presence and severity of bleeding every morning in an electronic diary (eDiary) according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:
- 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
- 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
- 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
- 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
- 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
- 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.
A day with moderate to very heavy bleeding is defined as a days with a bleeding score ≥ 3.
Measured: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3
Participants recorded the previous days' presence and severity of bleeding every morning in an eDiary according to the Mansfield-Voda-Jorgenson Menstrual Bleeding Scale:
- 1 (Spotting): A drop or 2 of blood, not even requiring sanitary protection.
- 2 (Very light): Needing to change the least absorbent tampon or pad 1 to 2 times per day.
- 3 (Light): Needing to change a low or regular absorbency tampon or pad 2 or 3 times per day.
- 4 (Moderate): Needing to change a regular absorbency tampon or pad every 3 to 4 hours.
- 5 (Heavy): Needing to change a high absorbency tampon or pad every 3 to 4 hours.
- 6 (Very heavy/gushing): Very heavy bleeding, protection hardly works at all; needing to change the highest absorbency tampon or pad every hour or 2.
Any bleeding is defined as a score ≥ 1 and moderate to very heavy bleeding is defined as a score ≥ 3.
Measured: Month 3 (average bleeding score over days 61 to 90)
Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment
Suppression of bleeding is defined as no record of bleeding (spotting allowed) in the e-diary and no record of bleeding Indicated in the alkaline hematin data during the last 56 days of treatment.
Amenorrhea is defined as no record of bleeding or spotting indicated in the e-diary and no record of bleeding or spotting Indicated in the alkaline hematin data during the last 56 days of treatment.
Measured: The last 56 days of treatment (approximately days 33 to 90)
Percent Change From Baseline to Month 3 in Uterine Volume
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Measured: Baseline and month 3
Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit
Uterine volume was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Measured: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Measured: Baseline and month 3
Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit
The volume of the largest fibroid was determined using transabdominal ultrasound. The images were analyzed by a central imaging center.
Measured: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
The UFS-QoL is a disease-specific, self-administered, validated questionnaire developed to evaluate the symptoms associated with uterine fibroids and their impact on health-related quality of life (HRQL) in women with symptomatic uterine fibroids. The questionnaire consists of 37 questions, divided into 2 parts: 1) an 8-item symptom severity scale and 2) a 29-item HRQL subscale comprising 6 domains (concern, activities, energy/mood, control, self-consiousness, and sexual function), with a 4-week recall. All items are scored on a 5-point scale, ranging from "not at all" to "a very great deal" for symptom severity items and "none of the time" to "all of the time" for the HRQL items. Symptom severity and HRQL subscale scores were summed and transformed into a 0 to 100 point scale to provide a total score for each of the 2 components.
Lower symptom severity scores indicate better quality of life and higher total HRQL scores indicate better quality of life.
Measured: Baseline and month 3
Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores
The uterine fibroid daily symptom scale is self-administered questionnaire, with a scale that ranges from 0 to 10 for the symptoms of pelvic pain, fatigue, and cramping and the impact of uterine fibroids on the subject's daily life, with 0 being the absence of the symptom and 10 being the worst severity of the symptoms or completely preventing the subjects from performing daily activities. Participants self-reported values daily in the e-Diary.
Measured: Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
The Subject Intention Questionnaire (SSIQ) is a non-validated, exploratory questionnaires intended to evaluate the subject's intent to undergo surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to consider surgery) to 10 (very likely to consider surgery).
SSIQ included the 2 following questions:
1. How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now?
2. How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?
Measured: Baseline and month 3
Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
The Physician Intention Questionnaire (PSIQ) is a non-validated, exploratory questionnaire intended to evaluate the investigator's intent to recommend surgical procedures if current endometriosis-associated symptoms continued. The scoring scale ranged from 0 (not at all likely to recommend surgery) to 10 (very likely to recommend surgery).
The PSIQ included the 2 following questions:
1. How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now?
2. How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?
Measured: Baseline and month 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Sep 201117 May 2014

First posted28 Sep 2011 (estimated)
Study start8 Sep 2011
Primary completionNov 2013
Study completion17 May 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Heavy Uterine BleedingStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 271 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01441635
Sponsor's protocol ID: M12-663
Status last verified: Jul 2021
First submitted: 6 Sep 2011
Last updated: 13 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

Archer DF, Stewart EA, Jain RI, Feldman RA, Lukes AS, North JD, Soliman AM, Gao J, Ng JW, Chwalisz K. Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study. Fertil Steril. 2017 Jul;108(1):152-160.e4. doi: 10.1016/j.fertnstert.2017.05.006. Epub 2017 Jun 1.
PubMed 28579415
Coyne KS, Soliman AM, Margolis MK, Thompson CL, Chwalisz K. Validation of the 4 week recall version of the Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) Questionnaire. Curr Med Res Opin. 2017 Feb;33(2):193-200. doi: 10.1080/03007995.2016.1248382. Epub 2016 Nov 18.
PubMed 27733082

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Heavy Uterine Bleeding trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01441635
Acronym / sponsor ID: M12-663
Conditions: Heavy Uterine Bleeding, Uterine Fibroids
Keywords: Uterine Fibroids, Heavy Uterine Bleeding, Elagolix, Menorrhagia, ABT-620, Leiomyomata, Elagolix sodium
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 271 participants (actual)
Lead sponsor: AbbVie (prior sponsor, Abbott)Industry (pharma, biotech, devices)
Study start: 8 Sep 2011 (actual)
Primary completion: Nov 2013 (actual)
Study completion: 17 May 2014 (actual)
First posted: 28 Sep 2011 (estimated)
Results: Posted 15 Jul 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 10

Arm	Type	Receives
Cohort 4 Elagolix 400 mg QD	Experimental	Drug: ElagolixParticipants received elagolix 400 mg once a day (QD) for 3 months.
Cohort 4 Elagolix 100 mg BID	Experimental	Drug: ElagolixParticipants received elagolix 100 mg twice a day (BID) for 3 months.
Cohort 4 Placebo	Placebo comparator	Drug: PlaceboParticipants received placebo to elagolix BID for 3 months.
Cohort 1 Elagolix 200 mg BID	Experimental	Drug: ElagolixParticipants received elagolix 200 mg twice a day for 3 months.
Cohort 1 Placebo	Placebo comparator	Drug: PlaceboParticipants received placebo to elagolix twice a day for 3 months.
Cohort 3 Elagolix 200 mg BID + LD E2/NETA	Placebo comparator	Drug: Elagolix, Drug: Estradiol/Norethindrone acetate (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.
Cohort 5 Elagolix 600 mg QD	Experimental	Drug: ElagolixParticipants received elagolix 600 mg once a day for 3 months.
Cohort 2 Elagolix 300 mg BID	Experimental	Drug: ElagolixParticipants received elagolix 300 mg twice a day for 3 months.
Cohort 2 Placebo	Experimental	Drug: PlaceboParticipants received placebo to elagolix BID for 3 months.
Cohort 6 Elagolix 300 mg BID + CEP	Experimental	Drug: Elagolix, Drug: Estradiol, Drug: ProgesteroneParticipants 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.

Who may qualify

Ages: 20 to 49 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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:
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.

Key exclusion criteria (8 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ElagolixAlso: ABT-620Elagolix tablets	Drug	Cohort 1 Elagolix 200 mg BID, Cohort 2 Elagolix 300 mg BID, Cohort 3 Elagolix 200 mg BID + LD E2/NETA, Cohort 4 Elagolix 100 mg BID, Cohort 4 Elagolix 400 mg QD, Cohort 5 Elagolix 600 mg QD, Cohort 6 Elagolix 300 mg BID + CEP
PlaceboMatching placebo tablets	Drug	Cohort 1 Placebo, Cohort 2 Placebo, Cohort 4 Placebo
Estradiol/Norethindrone acetate (E2/NETA)Also: Activella®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.	Drug	Cohort 3 Elagolix 200 mg BID + LD E2/NETA
EstradiolAlso: Estrace®1.0 mg micronized estradiol tablets administered once a day	Drug	Cohort 6 Elagolix 300 mg BID + CEP
ProgesteroneAlso: Prometrium®Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle	Drug	Cohort 6 Elagolix 300 mg BID + CEP

Primary outcome

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.

19 secondary outcomes

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)
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)
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)
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)
Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3
Time frame: Baseline and Month 3
Change in Hemoglobin Concentration From Baseline to Month 3
Time frame: Baseline and Month 3
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)
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)
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)
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)
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)
Percent Change From Baseline to Month 3 in Uterine Volume
Time frame: Baseline and month 3
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.
Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
Time frame: Baseline and month 3
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.
Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
Time frame: Baseline and month 3
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)
Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
Time frame: Baseline and month 3
Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
Time frame: Baseline and month 3

Results and safety

Results posted to the registry on 15 Jul 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 4 Elagolix 400 mg QD	32	26
Cohort 4 Elagolix 100 mg BID	33	27
Cohort 4 Placebo	16	13
Cohort 1 Elagolix 200 mg BID	35	28
Cohort 1 Placebo	18	16
Cohort 3 Elagolix 200 mg BID + LD E2/NETA	34	29
Cohort 5 Elagolix 600 mg QD	30	24
Cohort 2 Elagolix 300 mg BID	30	26
Cohort 2 Placebo	16	14
Cohort 6 Elagolix 300 mg BID + CEP	27	25

Primary outcome: 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). Mean (Standard Deviation). Unit: mL

Measure	Cohort 4 Elagolix 400 mg QD n = 31	Cohort 4 Elagolix 100 mg BID n = 31	Cohort 4 Placebo n = 15	Cohort 1 Elagolix 200 mg BID n = 32	Cohort 1 Placebo n = 18	Cohort 3 Elagolix 200 mg BID + LD E2/NETA n = 33	Cohort 5 Elagolix 600 mg QD n = 28	Cohort 2 Elagolix 300 mg BID n = 30	Cohort 2 Placebo n = 15	Cohort 6 Elagolix 300 mg BID + CEP n = 26
Baseline	213.70 (108.08)	269.36 (163.17)	321.73 (327.57)	335.11 (322.68)	251.72 (160.29)	247.70 (177.72)	215.62 (122.84)	206.27 (125.08)	349.17 (424.12)	257.99 (207.33)
Change from Baseline	-183.97 (132.19)	-184.69 (187.05)	-10.46 (85.04)	-272.97 (271.39)	-79.00 (161.33)	-192.33 (191.51)	-189.05 (151.15)	-202.57 (127.93)	-175.31 (342.14)	-216.15 (157.08)

Cohort 4 Elagolix 400 mg QD vs Cohort 4 Placebo: LS Mean Difference: -205.9 (95% CI -295.77 to -116.01), p < 0.001, ANCOVA
Cohort 4 Elagolix 100 mg BID vs Cohort 4 Placebo: LS Mean Difference: -189.9 (95% CI -278.33 to -101.53), p < 0.001, ANCOVA
Cohort 1 Elagolix 200 mg BID vs Cohort 1 Placebo: LS Mean Difference: -138.0 (95% CI -220.18 to -55.76), p = 0.001, ANCOVA

Population analysed: Randomized (Cohorts 1, 2, and 4) or treated (Cohorts 3, 5, and 6) participants, excluding participants with less than 28 days of treatment. Last observation carried forward (LOCF) imputation was used for participants with no MBL volume reported by alkaline hematin method but with light to heavy bleeding reported in the eDiary.

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the date of the first dose of study drug through up to 30 days after the last dose of study drug, up to 4 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1 Placebo	1 of 18 (5.6%)	8 of 18 (44.4%)	0 of 18
Cohort 1 Elagolix 200 mg BID	0 of 35 (0%)	26 of 35 (74.3%)	0 of 35
Cohort 2 Placebo	0 of 16 (0%)	10 of 16 (62.5%)	0 of 16
Cohort 2 Elagolix 300 mg BID	1 of 30 (3.3%)	20 of 30 (66.7%)	0 of 30
Cohort 3 Elagolix 200 mg BID + LD E2/NETA	0 of 34 (0%)	20 of 34 (58.8%)	0 of 34
Cohort 4 Placebo	2 of 16 (12.5%)	9 of 16 (56.3%)	0 of 16
Cohort 4 Elagolix 100 mg BID	2 of 33 (6.1%)	20 of 33 (60.6%)	0 of 33
Cohort 4 Golix 400 mg QD	0 of 32 (0%)	24 of 32 (75%)	0 of 32
Cohort 5 Elagolix 600 mg QD	2 of 30 (6.7%)	22 of 30 (73.3%)	0 of 30
Cohort 6 Elagolix 300 mg BID + CEP	0 of 27 (0%)	11 of 27 (40.7%)	0 of 27

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28579415Archer DF, Stewart EA, Jain RI, Feldman RA, Lukes AS, North JD, Soliman AM, Gao J, Ng JW, Chwalisz K. Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study. Fertil Steril. 2017 Jul;108(1):152-160.e4. doi: 10.1016/j.fertnstert.2017.05.006. Epub 2017 Jun 1.
Derived from this study: PubMed 27733082Coyne KS, Soliman AM, Margolis MK, Thompson CL, Chwalisz K. Validation of the 4 week recall version of the Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) Questionnaire. Curr Med Res Opin. 2017 Feb;33(2):193-200. doi: 10.1080/03007995.2016.1248382. Epub 2016 Nov 18.
Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

AbbVie Inc. study director

AbbVie

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Elagolix, Estradiol/Norethindrone acetate (E2/NETA) and Estradiol in people with Heavy Uterine Bleeding and Uterine Fibroids, run by AbbVie (prior sponsor, Abbott).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01441635, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2021.