PGL4001 Versus Placebo 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 with concomitant iron administration versus placebo with concomitant iron administration, 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, 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

Conditions
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Uterine Myomas

Intervention / Treatment
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* Drug: PGL4001 (ulipristal) and iron
* Drug: PGL4001 matching placebo and iron
* Drug: PGL4001 (ulipristal) and iron


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 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.

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 5mg)<br>PGL4001 5 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ | Drug: PGL4001 (ulipristal) and iron<br>* tablets<br>* Other names: Ulipristal acetate;|
| Experimental: B (PGL4001 10mg)<br>PGL4001 10 mg (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ | Drug: PGL4001 (ulipristal) and iron<br>* Tablets<br>* Other names: Ulipristal acetate;|
| Placebo Comparator: C (placebo)<br>PGL4001 matching placebo (oral tablets) with concomitant oral administration of 1 tablet containing 80 mg Fe2+ | Drug: PGL4001 matching placebo and iron<br>* tablets<br>* Other names: Placebo of ulipristal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Co-primary Endpoint: Percentage of Subjects With Reduction in Uterine Bleeding Defined as a Pictorial Blood-loss Assessment Chart (PBAC) Score <75 at End-of-treatment Visit (Week 13) | 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. | Week 13 visit | 
| Co-primary Endpoint: Percent Change in Total Myoma Volume Assessed by Magnetic Resonance Imaging (MRI) From Screening to End of Treatment Visit (Week 13 Visit) | Percent change in total fibroid volume from screening to end of treatment visit (Week 13 visit) assessed by MRI and read centrally by a radiologist who was unaware of the study-group assignments. The total fibroid volume was the sum of the individual fibroid volumes. | Week 13 |