PGL4001 Versus GnRH-agonist in Uterine Myomas

Study Overview
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Brief Summary
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This trial will assess the efficacy and safety of PGL4001 versus GnRH agonist, over a 3-month period for the pre-operative treatment of pre-menopausal women suffering from excessive uterine bleeding due to uterine myoma.

Official Title
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A Phase III, Randomised, Parallel Group, Double-blind, Double-dummy, Active Comparator-controlled, Multicenter Study to Assess the Efficacy and Safety of PGL4001 vs GnRH-agonist for Pre-operative Ttt of Symptomatic Uterine Myomas

Conditions
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Uterine Myomas

Intervention / Treatment
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* Drug: PGL4001
* Drug: leuprorelin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (PGL4001 5 mg)<br>Drug: PGL4001 5mg (oral tablets) and leuproreline matching placebo (intramuscular injection) | Drug: PGL4001<br>* tablets<br>* Other names: Ulipristal acetate;|
| Experimental: B (PGL4001 10mg)<br>Drug: PGL4001 10 mg (oral tablets) and leuproreline matching placebo (intramuscular injection) | Drug: PGL4001<br>* tablets<br>* Other names: Ulipristal acetate;|
| Active Comparator: C (GnRH-agonist)<br>PGL4001 matching placebo (oral tablets) and leuprorelin 3.75 mg (intramuscular injection) | Drug: leuprorelin<br>* solution for injection<br>* Other names: GnRH-agonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Reduction of Uterine Bleeding at Week 13 Visit Defined as Pictorial Blood-loss Assessment Chart (PBAC) Score < 75 at End-of-treatment Visit (Week 13 Visit) | Uterine bleeding was assessed with the use of the PBAC, a validated self-reporting method to estimate menstrual blood loss. Patients recorded daily the number of tampons and towels used and the degree to which individual items were soiled with blood (plus small or large clots). Monthly scores range from 0 (amenorrhea) to more than 500, with higher numbers indicating more bleeding. A slightly stained tampon/towel scores 1, a partially stained tampon/towel scores 5, a completely saturated tampon scores 10 and a completely saturated towel scores 20. Small clots/flooding (2cm) score 1. Large clots/flooding (3cm) score 5. Menorrhagia is defined as a PBAC > 100 during one menstrual period which approximates to a blood loss of > 80 mL. A PBAC of 400 corresponds to a blood loss of around 300 mL or approximately 80 tampons/towels used. The week 13 PBAC score was calculated using the last 28 days of treatment. | 3 months | 
| Co-primary Safety Endpoint: Serum Estradiol Levels at End of Treatment Visit (Week 13 Visit) for PGL4001 Compared With GnRHagonist | Measured by log 10 (log pg/ml) transformed values for estradiol (E2) in blood samples | Week 13 visit | 
| Co-primary Safety Endpoint: % of Subjects Reporting Moderate or Severe Hot Flushes as Adverse Events Throughout the Treatment Period for PGL4001 Compared With GnRH-agonist | Difference in percentage of subjects reporting moderate or severe hot flushes: Frequency and severity of this adverse event(as spontaneously reported by patients or elicited by nonleading questions) were recorded on standard forms at every visit up to week 17. | Up to week 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Total Volume of the Three Largest Myomas From Baseline to Week 13 | Assessment of PGL4001 capacity to decrease volume of the three largest myomas was performed at each center by means of ultrasonography at baseline and at week 13. The total volume of the three largest myomas assessed at screening and at end-of-treatment visit (Week 13) was analysed on a logarithm transformed scale (to base 10). | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Myomas