A Phase III, randomised, parallel group, double-blind, double-dummy, active comparator -controlled, multi-center study to assess the efficacy and safety of PGL4001 (ulipristal) versus GnRH-agonist (leuprorelin 3.75mg) for pre-operative treatment of symptomatic uterine myomas. - PEARL II, PGL4001 versus GnRH-agonist in uterine myomas

Conditions: terine myomas are benign, monoclonal, hormone sensitive, smooth muscle tumors of the uterus. It is the most common tumor of the female reproductive tract in pre-menopausal women and mostly asymptomatic. When symptomatic, its cardinal symptoms are heavy uterine bleeding, anaemia, abdominal pressure, abdominal pain, urinary frequency and infertility. Myomas affect approximately 40% of women between 35 and 55 years.
MedDRA version: 9.1Level: LLTClassification code 10046801Term: Uterine myoma

Registration Number: EUCTR2008-001805-40-NL

Lead Sponsor: PregLem S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 300

Inclusion Criteria

To be eligible for inclusion into this study, the subjects must fulfil all of the following criteria:
1.The subject must provide written informed consent prior to any study related procedures.
2.The subject must be a pre-menopausal woman between 18 and 50 years inclusive.
3.The subject must have a PBAC score >100 during day 1 to day 8 of menstruation preceding the baseline visit.
4.The subject must have a myomatous uterus = 16 weeks.
5.The subject must have at least one uterine myoma of = 3 cm diameter in size and no myoma larger than 10 cm diameter in size diagnosed by ultrasound.
6.The subject must be eligible for one of these surgical procedures: i.e. hysterectomy, myomectomy, uterine artery embolization or endometrial ablation within 13 weeks and up to 14 weeks from baseline study visit.
7.The subject must have a clinical breast examination without significant findings at the screening visit.
8.The subject must have no clinically significant findings at PAP smear, performed within the past 12 months or at the screening visit.
9.If of childbearing potential the subject must be practicing a non-hormonal method of contraception as listed below:
-Sexual abstinence
-Diaphragms
-Condom or partner with a vasectomy performed at least 6 months prior to the study and confirmed azoospermia.
10.If of non childbearing potential, the subject must have had a tubal ligation sterilisation at least two months before study start.
11.The subject must have a BMI = 18 and = 40.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

To be eligible for inclusion in this study the subjects must not meet any of the following criteria:
1.The subject has a history of uterus surgery (except caesarean section or cervical conisation), endometrial ablation or uterine artery embolization.
2.The subject has a history of or current uterine, cervical, ovarian or breast cancer.
3.The subject has a history of or current endometrium atypical hyperplasia in the screening biopsy or in a biopsy performed within the past 6 months.
4.The subject has a condition requiring immediate blood transfusion or a level of Hb = 6 g/dL.
5.The subject has a known hemoglobinopathy (i.e. Sickel Cell anaemia and Thalassamia).
6.The subject has a known severe coagulation disorder.
7.The subject has a large uterine polyp (> 2cm).
8.The subject has one or more ovarian cysts = 4cm in diameter diagnosed by US.
9.The subject has a history of or current treatment for myoma with a SPRM or a GnRH-agonist.
10.The subject has been taking:
a.Treatments with progestins (systemic or progestin releasing intra-uterine system) or an oral contraceptive: within the month before the screening visit.
b.Acetylsalicylic acid and/or mefenamic acid: within one week before the screening visit,
c.Systemic glucocorticoid treatments and/or systemic depot glucocorticoid treatments within one week or two months before the screening visit, respectively.
11.The subject is likely to require treatment during the study with drugs that are not permitted by the study protocol: progestins (systemic or progestin releasing intra-uterine system), oral contraceptives, systemic glucocorticoids (oral and injectable), acetylsalicylic acid and/or mefenamic acid.
12.The subject has a history of or known current osteoporosis.
13.The subject has abnormal hepatic function at study entry (defined as AST, ALT, ?GT, alkaline phosphatase or total bilirubin above 2 ULN).
14.The subject has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study.
15.The subject has a current (within twelve months) problem with alcohol or drug abuse.
16.The subject has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
17.The subject has abnormal baseline findings, any other medical condition(s) or psychiatric condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the subject’s safety or interfere with study evaluations.
18.The subject has an allergy to GnRH agonist, SPRMs or progestins or any of the ingredients of the study drug tablet (see list of ingredients in the investigator’s brochure),
19.The subject is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.