Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicentre, Clinical Study Investigating the Efficacy and Safety of 3-months Open-label Treatment With PGL4001, Followed by a Randomised, Double-blind Placebo Controlled Period of 10 Days Treatment With Progestin, in Subjects With Myomas and Heavy Uterine Bleeding.
Brief Summary: This is a multicentre, Phase III, efficacy and safety open-label study with PGL4001 10mg once daily for 3 months, blinded towards the administration of progestin or placebo after end of PGL4001 treatment.


Options:
A: Inclusion Criteria:

* Be a pre-menopausal woman between 18 and 50 years inclusive.
* Have excessive uterine bleeding due to myoma
* Have a myomatous uterus with at least one myoma of ≥ 3 cm diameter in size
* Be eligible for one surgical procedure: e.g. hysterectomy, myomectomy or others.
* If of childbearing potential the subject must be practicing a non-hormonal method of contraception.
* Have a Body Mass Index (BMI) ≥ 18 and ≤ 40.

Exclusion Criteria:

* Has a history of or current uterine, cervical, ovarian or breast cancer.
* Has a history of or current endometrium atypical hyperplasia or adenocarcinoma.
* Has a known severe coagulation disorder.
* Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRH-agonist.
* Has a history of or known current osteoporosis.
* Has abnormal hepatic function at study entry.
* Has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study.
* Has a current (within twelve months) problem with alcohol or drug abuse.
* Is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.
B: 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.
C: Inclusion Criteria:

* Be a pre-menopausal woman between 18 and 50 years inclusive.
* Have excessive uterine bleeding due to myoma.
* Have a myoma-related anaemia.
* Have a myomatous uterus with at least one myoma of ≥ 3 cm diameter in size.
* Be eligible for one surgical procedure: e.g. hysterectomy, myomectomy or others.
* If of childbearing potential the subject must be practicing a non-hormonal method of contraception.
* Have a Body Mass Index (BMI) ≥ 18 and ≤ 40.

Exclusion Criteria:

* Has a history of or current uterine, cervical, ovarian or breast cancer.
* Has a history of or current endometrium atypical hyperplasia.
* Has a known severe coagulation disorder.
* Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRH-agonist.
* Has abnormal hepatic function at study entry.
* Has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study.
* Has a current (within twelve months) problem with alcohol or drug abuse.
* Is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.
D: Inclusion Criteria:

* Subject is a pre-menopausal woman aged between 18 and 48 years inclusive.
* Subject with a Body Mass Index ≥18 and ≤40.
* Subject with myomatous uterus size \< 16 weeks.
* Subject must have at least one uterine myoma of at least 3 cm diameter in size and no myoma larger than 10 cm diameter diagnosed by ultrasound.
* Subject complained of strong uterine bleeding.
* Subject is eligible for hysterectomy or myomectomy.
* Females of childbearing potential have to practice a non-hormonal method of contraception.

Exclusion Criteria:

* Subject has a history of or current uterus, cervix, ovarian or breast cancer.
* Subject has a history of endometrium hyperplasia or adenocarcinoma in a biopsy performed within the past 6 months or similar lesions in the screening biopsy.
* Subject has a known severe coagulation disorder.
* Subject has a history of treatment for myoma with a SPRM, including ulipristal acetate.
* Subject has abnormal hepatic function at study entry.

Answer: D