Please select the eligibility criteria that correspond to the clinical trial below.
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
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.


Options:
A: INCLUSION CRITERIA:

* Female gender-to evaluate effects in the target population for clinical trials.
* History of uterine leiomyoma causing symptoms of bleeding, pressure, or pain, as defined by the American College of Obstetrics and Gynecology (ACOG) practice bulletin:
* Excessive uterine bleeding will be evidenced by either of the following-profuse bleeding with flooding or clots or repetitive periods lasting for more than 8 days; or anemia due to acute or chronic blood loss;

OR

* Pelvic discomfort caused by leiomyomata, either acute and severe or chronic lower abdominal or low back pressure or bladder pressure with urinary frequency not due to urinary tract infection.
* Uterine leiomyoma(ta) of at least 2 cm size.
* In good health. Chronic medication use is acceptable except for glucocorticoid use. Other chronic medication use may be acceptable at the discretion of the research team. Interval use of over-the-counter drugs is acceptable but must be recorded.
* Menstrual cycles of 24 - 35 days.
* Hemoglobin greater than 10 g/dL (for those wishing surgery); iron may be administered to improve red blood cell counts.
* Willing and able to comply with study requirements.
* Age 25 to 50.
* Using mechanical (condoms, diaphragms) sterilization or abstinence methods of contraception for the duration of the study.
* Negative urine pregnancy test.
* Body mass index (BMI) less than or equal to 33, if a surgical candidate or less than or equal to 35, if not a surgical candidate.
* Creatinine less than 1.3 mg/dL.
* Liver function tests within 130% of upper limit.
* If interested in hysterectomy, no desire for fertility.

EXCLUSION CRITERIA:

* Significant abnormalities in the history, physical or laboratory examination.
* Pregnancy.
* Lactation.
* Use of oral, injectable or inhaled glucocorticoids or megestrol within the last year.
* Unexplained vaginal bleeding.
* History of malignancy within the past 5 years.
* Use of estrogen or progesterone-containing compounds, such as oral contraceptives and hormone replacement therapy, within 8 weeks of study entry, including transdermal, injectable, vaginal and oral preparations.
* Use of agents known to induce hepatic P450 enzymes; use of imidazoles.
* Current use of Gonadotropin-releasing hormone (GnRH) analogs or other compounds that affect menstrual cyclicity.
* Follicle stimulating hormone (FSH) greater than 20 IU/mL.
* Untreated cervical dysplasia.
* Need for interval use of narcotics.
* Abnormal adnexal/ovarian mass.
* Use of herbal medication having estrogenic or antiestrogenic effects within the past 3 months.
* Contradiction to anesthesia, for women planning surgery.
* Genetic causes of leiomyomata.
* Previous participation in the study.
* Known recent rapid growth of fibroids, defined as a doubling in size in six months.
B: Inclusion Criteria:

* Women between 18 and 49 years of age
* Diagnosis of either 1 or more uterine fibroids
* History of regular menstrual cycles of 21 to 35 days in length.

Exclusion Criteria:

* Any abnormal lab result the study-doctor considers significant
* History of severe reaction to or current use of hormone therapy
* History of osteoporosis or other bone disease
* History of uterine artery embolization, cryomyolysis, or electrical myolysis
* Subject currently breast feeding
* Hemoglobin \< 8 g/dL at baseline
C: Inclusion Criteria:

* Subject is pre-menopausal female 18 to 51 years of age at Screening.
* Subject has diagnosis of uterine fibroids documented by a Pelvic Ultrasound.
* Subject has heavy uterine bleeding associated with uterine fibroids.

Exclusion Criteria:

* Subject has had a myomectomy, uterine artery embolization or high intensity focused ultrasound for fibroid destruction within 6 months prior to Screening or endometrial ablation within 5 years prior to Screening.
* 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, schizophrenia, bipolar disorder), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes. Subject has any history of attempted suicide.
* Subject has a history of clinically significant condition(s) including but not limited to: \* Symptomatic Endometriosis \* Epilepsy or seizures \* Type 1 diabetes \* Chronic kidney disease \* Any cancer (except treated basal cell carcinoma of the skin), including breast or ovarian cancer or subject has taken any systemic cancer chemotherapy
D: 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

Answer: D