Clinical trial NCT01441635: Safety and Efficacy of Elagolix in Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heavy Uterine Bleeding
Uterine Fibroids
Keywords: Uterine Fibroids
Heavy Uterine Bleeding
Elagolix
Menorrhagia
ABT-620
Leiomyomata
Elagolix sodium
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2011-09-28
Enrollment: 271
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Mean Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
timeFrame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
Secondary outcomes:
measure: Percent Change From Baseline to the Last 28 Days of Treatment in Menstrual Blood Loss (MBL)
timeFrame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
measure: Percentage of Participants With MBL < 80 mL and With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
timeFrame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
measure: Percentage of Participants With MBL < 80 mL During the Last 28 Days of Treatment
timeFrame: The last 28 days of treatment (approximately days 61 to 90)
measure: Percentage of Participants With a ≥ 50% Reduction From Baseline in MBL During the Last 28 Days of Treatment
timeFrame: Baseline (last menstrual cycle during the screening period) and the last 28 days of treatment (approximately days 61 to 90)
measure: Percentage of Participants With No Change, Decrease From Baseline, or Increase From Baseline in Hemoglobin at Month 3
timeFrame: Baseline and Month 3
measure: Change in Hemoglobin Concentration From Baseline to Month 3
timeFrame: Baseline and Month 3
measure: Change From Baseline to Month 3 in Uterine Bleeding Score
timeFrame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
measure: Change From Baseline to Month 3 in Percentage of Days With Any Uterine Bleeding
timeFrame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
measure: Change From Baseline to Month 3 in Percentage of Days With Moderate to Very Heavy Bleeding
timeFrame: Baseline (average bleeding score over the 30 days prior to first dose) and month 3 (average bleeding score over days 61 to 90)
measure: Percentage of Participants With Any Uterine Bleeding or Moderate to Very Heavy Uterine Bleeding at Month 3
timeFrame: Month 3 (average bleeding score over days 61 to 90)
measure: Percentage of Participants With Suppression of Bleeding (Spotting Allowed) or Amenorrhea During the Last 56 Days of Treatment
timeFrame: The last 56 days of treatment (approximately days 33 to 90)
measure: Percent Change From Baseline to Month 3 in Uterine Volume
timeFrame: Baseline and month 3
measure: Percentage of Participants With ≥ 25% Reduction in Uterine Volume at Month 3 / Final Visit
timeFrame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
measure: Percent Change From Baseline to Month 3 in Volume of the Largest Fibroid
timeFrame: Baseline and month 3
measure: Percentage of Participants With ≥ 25% Reduction in Volume of Largest Fibroid at Month 3 / Final Visit
timeFrame: Baseline and month 3 or the final visit during the treatment period for participants who prematurely discontinued.
measure: Change From Baseline to Month 3 in the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QoL)
timeFrame: Baseline and month 3
measure: Change From Baseline to Month 3 in the Uterine Fibroids Daily Symptom Scale Scores
timeFrame: Baseline (average score over the 30 days prior to first dose) and month 3 (average score over days 61 to 90)
measure: Change From Baseline to Month 3 in the Subject Surgery Intention Questionnaire (SSIQ) Version 2.0
timeFrame: Baseline and month 3
measure: Change From Baseline to Month 3 in the Physician Surgery Intention Questionnaire (PSIQ) Version 2.0
timeFrame: Baseline and month 3
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.