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

Uterine Fibroids Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01441635
• Other study ID #: M12-663
• Status: Completed
• Phase: Phase 2
• Start date: September 8, 2011
• Est. completion date: May 17, 2014

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 271
• Est. completion date: May 17, 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Heavy Uterine Bleeding
• Hemorrhage
• Leiomyoma
• Uterine Fibroids
• Uterine Hemorrhage

Intervention

Drug:
• Elagolix
Elagolix tablets
• Placebo
Matching placebo tablets
• 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.
• Estradiol
1.0 mg micronized estradiol tablets administered once a day
• Progesterone
Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Secondary	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.	Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Secondary	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.	Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Secondary	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.	The last 28 days of treatment (approximately days 61 to 90)
Secondary	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.	Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Secondary	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.	Baseline and Month 3
Secondary	Change in Hemoglobin Concentration From Baseline to Month 3		Baseline and Month 3
Secondary	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.	Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Secondary	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.	Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Secondary	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.	Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
Secondary	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.	Month 3 (average bleeding score over days 61 to 90)
Secondary	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.	The last 56 days of treatment (approximately days 33 to 90)
Secondary	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.	Baseline and month 3
Secondary	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.	Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Secondary	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.	Baseline and month 3
Secondary	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.	Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
Secondary	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.	Baseline and month 3
Secondary	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.	Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
Secondary	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: How likely are you to consider having myomectomy surgery to treat your uterine fibroid if your symptoms continue as they are now?; How likely are you to consider hysterectomy surgery if your uterine fibroid symptoms continue as they are now?	Baseline and month 3
Secondary	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: How likely are you to recommend myomectomy to treat this patient's uterine fibroid if her symptoms continue as they are now?; How likely are you to recommend definitive surgery hysterectomy for this patient if her uterine fibroid symptoms continue as they are now?	Baseline and month 3