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

AbbVie (prior sponsor, Abbott)271 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

271

Conditions

Heavy Uterine Bleeding Uterine Fibroids

Interventions

ElagolixDRUG

Elagolix tablets

PlaceboDRUG

Matching placebo tablets

Estradiol/Norethindrone acetate (E2/NETA)DRUG

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.

Eligibility

Sex: FEMALEMin age: 20 YearsMax age: 49 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)

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)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

1.0 mg micronized estradiol tablets administered once a day

ProgesteroneDRUG

Progesterone 200 mg administered during the last 12 days of the 28-day menstrual cycle

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

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.

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

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.

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

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.

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

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.

Time frame: 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.