A Phase III, randomized, parallel group, double-blind, placebo-controlled, multi-center study to assess the efficacy and safety of PGL4001 (ulipristal) versus placebo for pre-operative treatment of symptomatic uterine myomas - PGL4001 versus placebo in uterine myomas

• Conditions: terine myoma 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: EUCTR2008-001804-22-HU
• Lead Sponsor: PregLem S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-16
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 240

Inclusion Criteria

In order to be included, subject must:
1. Provide written informed consent prior to any study related procedures.
2. Be a pre-menopausal woman between 18 and 50 years inclusive.
3. Have a PBAC score >100 during day 1 to day 8 of menstruation preceding the baseline visit.
4. Have myoma-related anaemia defined as Hb = 10.2 g/dL. Absence of macrocytic anemia is to be proven by a mean corpuscular volume (MCV) = 104 fL.
5. Have a myomatous uterus = 16 weeks.
6. Have at least one uterine myoma of = 3 cm diameter in size but no myoma larger than 10 cm diameter in size confirmed by ultrasound.
7. 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.
8. Have a clinical breast examination without significant findings at the screening visit.
9. Have no clinically significant findings at Papanikolaou test (PAP) smear performed within the past 12 months or at the screening visit.
10. 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.
11. If of non childbearing potential, the subject must have had a tubal ligation sterilisation at least two months before study start.
12. Have a Body Mass Index (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

Subject will be excluded from participation, if she:
1. Has a history of uterus surgery (except caesarean section or cervical conisation), endometrial ablation or uterine artery embolization.
2. Has a history of or current uterine, cervical, ovarian or breast cancer.
3. The subject has:
- a history of atypical hyperplasia
- or a current endometrium hyperplasia (atypical or non atypical) or adenocarcinoma or similar lesions in the screening biopsy or in a biopsy performed within the past 6 months.
4. Has a condition requiring immediate blood transfusion or a level of Hb = 6 g/dL.
5. Has a known hemoglobinopathy (i.e. Sickel Cell anaemia and Thalassamia).
6. Has a known severe coagulation disorder.
7. Has a large uterine polyp (> 2cm).
8. Has one or more ovarian cysts = 4cm in diameter diagnosed by Ultrasound (US).
9. Presents with any metallic, ferro-magnetic or electronic implant and/or device which may interfere with the MRI examination or potentially pose a risk (e.g. internal (implanted) defibrillator, implanted spinal cord stimulator, IVC filters, cochlear (ear) implant, clips used on brain aneurysms, artificial heart valves, implanted drug infusion ports, infusion catheter, IUD, implanted electronic device, including a cardiac pacemaker, artificial limbs or metallic joint prostheses, implanted nerve stimulators, metal pins, screws, plates or surgical staples, metallic foreign body fragments (metal splinter) in orbit, congestive heart failure, claustrophobia, pedicle screws / anterior interbody cages in spine).
10. Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a Gonadotropin Releasing Hormone agonist (GnRH-agonist).
11. Has been taking:
-Treatments with progestins (systemic or progestin releasing intra-uterine system) or an oral contraceptive: within the month before the screening visit,
-Acetylsalicylic acid, mefenamic acid, anticoagulants such as cumarins and/or antifibrinolytic drugs such as tranexamic acid: within one week before the screening visit,
-Systemic glucocorticoid treatments and/or systemic depot glucocorticoid treatments within one week or two months before the screening visit, respectively.
12. 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, mefenamic acid, anticoagulants such as cumarins and/or antifibrinolytic drugs such as tranexamic acid.
13. Has abnormal hepatic function at study entry (defined as Aspartate transaminase (AST), Alanine transaminase (ALT), Gamma Glutamine Transferase (?GT), alkaline phosphatase or total bilirubin above 2 Upper Limit of Normal range (ULN)).
14. Has a positive pregnancy test at baseline or is nursing or planning a pregnancy during the course of the study.
15. Has a current (within twelve months) problem with alcohol or drug abuse.
16. 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. 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.This does include the use of agents known to induce or inhibit

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objectives are to demonstrate superior efficacy of PGL4001 with concomitant iron administration versus placebo with concomitant iron administration:<br>- To reduce excessive uterine bleeding prior to surgery<br> and<br>- To reduce total myoma volume prior to surgery.<br>;Secondary Objective: Secondary objectives are <br>- To demonstrate superior efficacy of PGL4001 with concomitant iron administration versus placebo with concomitant iron administration in correcting anaemia caused by uterine myomas.<br>- To demonstrate improvement in myoma-related symptoms, such as pain.<br>- To assess PGL4001 capacity to decrease uterine volume.<br>;Primary end point(s): Two co-primary endpoints are defined:<br>Percentage of subjects with reduction in uterine bleeding defined as a PBAC score < 75 at end-of-treatment visit (Week 13 visit) and<br>Change in total myoma volume assessed by Magnetic resonance imaging (MRI) from screening to end of treatment visit (Week 13 visit).<br>