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

• Conditions: symptomatic uterine myoma; MedDRA version: 9.1Level: LLTClassification code 10046801Term: Uterine myoma

• Registration Number: EUCTR2008-001805-40-IT
• Lead Sponsor: PREGLEM SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-23
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 300

Inclusion Criteria

In order to be included, subject must:
Provide written informed consent prior to any study related procedures.
Be a pre-menopausal woman between 18 and 50 years inclusive.
Have a PBAC score >100 during day 1 to day 8 of menstruation preceding the baseline visit.
Have a myomatous uterus volume ≤ 16 weeks.
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.
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.
Have a clinical breast examination without significant findings at the screening visit.
Have no clinically significant findings at Papanikolaou test (PAP) smear, performed within the past 12 months or at the screening visit.
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.
If of non childbearing potential, the subject must have had a tubal ligation sterilisation at least two months before study start.
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:
Has a history of uterus surgery (except caesarean section or cervical conisation), endometrial ablation or uterine artery embolization.
Has a history of or current uterine, cervical, ovarian or breast cancer.
Has a history of or current endometrium atypical hyperplasia or adenocarcinoma or similar lesions in the screening biopsy or in a biopsy performed within the past 6 months.
Has a condition requiring immediate blood transfusion or a level of Hb ≤ 6 g/dL.
Has a known hemoglobinopathy (i.e. Sickel Cell anaemia and Thalassämia).
Has a known severe coagulation disorder.
Has a large uterine polyp (> 2cm).
Has one or more ovarian cysts ≥ 4cm in diameter diagnosed by Ultrasound (US).
Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM) or a GnRH-agonist.
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 and/or mefenamic 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.
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.
Has a history of or known current osteoporosis.
Has abnormal hepatic function at study entry (defined as Aspartate transaminase (AST), Alanine transaminase (ALT), Gamma Glutamine Transferase (γGT), alkaline phosphatase or total bilirubin above 2 Upper Limit of Normal range (ULN)).
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.
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.
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.
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),
Is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective of this study is to demonstrate non inferior efficacy of PGL4001 versus GnRH-agonist to reduce, prior to surgery, excessive uterine bleeding caused by uterine myomas.;Secondary Objective: Secondary objectives are to demonstrate improvement over baseline in myoma-related symptoms such as impaired Quality of Life (QoL) and pain, and to assess PGL4001 capacity to decrease uterine volume as well as volume of the three largest myomas;Primary end point(s): Primary safety endpoint are the:<br>- Mean serum E2 levels at end of treatment visit (Week 13 visit) for PGL4001 compared with GnRH-agonist.<br>- Percentage of subjects reporting moderate or severe hot flushes as adverse events throughout the treatment period for PGL4001 compared with GnRH-agonist.