PGL4001 Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata

Study Overview
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Brief Summary
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Phase III, multicentre, randomized, double-blind, parallel group, long-term study investigating the efficacy and safety of the 5mg and 10mg doses of PGL4001 for the treatment of uterine myoma.

Detailed Description
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The target population is composed of pre-menopausal women with symptomatic uterine myoma(s) characterised by heavy bleeding.The main objective of this study is to assess the sustained efficacy and safety of long term on-off treatment with PGL4001 5 or 10mg doses on uterine bleeding, myoma size, pain and quality of life.

Official Title
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A Phase III, Multicentre, Randomized, Double-blind Clinical Study, Investigating the Efficacy and Safety of Repeated 12-week Courses of Daily 5mg or 10mg Doses of PGL4001 for the Long-term Management of Symptomatic Uterine Fibroids

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Drug: PGL4001 5 mg
* Drug: PGL4001 10 mg


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 a Body Mass Index (BMI) ≥ 18 and ≤ 40. Have FSH levels ≤ 20 mIU/mL Have excessive uterine bleeding due to myoma. Have regular menstrual cycles Have a myomatous uterus < 16 weeks with at least one myoma ≥ 3 cm in diameter. If of childbearing potential the subject must be practicing a non-hormonal method of contraception. 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). Has abnormal hepatic function at study entry. Has a positive pregnancy test, 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ulipristal acetate (PGL4001) 5mg<br>All subjects will be asked to take a 150mg size tablet (PGL4001 5mg or matching placebo: placebo 5) orally daily for repeated periods 84 days. The first treatment course will start on the first 4 days of menstruation and will be orally administered, once daily (1 tablet of 150mg size), for 84 days. The following three treatment courses should be started in the first two days of a menstrual period. | Drug: PGL4001 5 mg<br>* PGL4001 5 mg daily administration<br>* Other names: Ulipristal Acetate, Esmya;|
| Experimental: Ulipristal acetate (PGL4001) 10mg<br>All subjects will be asked to take a 300mg size tablet (PGL4001 10mg or matching placebo: placebo 10 ) orally daily for repeated periods 84 days. The first treatment course will start on the first 4 days of menstruation and will be orally administered, once daily (1 tablet of 300mg size), for 84 days. The following three treatment courses should be started in the first two days of a menstrual period. | Drug: PGL4001 10 mg<br>* PGL4001 10mg daily administration<br>* Other names: Ulipristal Acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses | Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. Subjects need to be in amenorrhoea at the end of all four treatment courses, i.e for at least 4x35 days. | 18 months study duration per subject (4 3-month intermittent treatment courses) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4 | Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. | After 18 months | 
| Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses | Controlled bleeding was defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a treatment course. Subjects need to be in controlled bleeding at the end of all 4 treatment courses i.e. for at least 4x56 days. | After 18 months | 
| Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids | For the 3 largest myomas at baseline and the 3 largest myomas at the end of treatment course 4 identified by transvaginal ultrasound, length, height and depth were measured and the volume was estimated by applying the equation for the voulme of an ellipsoid (length x height x depht x π/6). Subjects were exposed to 4 3-month intermittent courses. | After 18 months | 
| Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL) | Quality of Life was assessed using a validated questionnaire measuring uterine fibroid symptom severity (UFSQoL) where lower scores indicate fewer symtoms and where a level of 23 has been reported for healthy subject (scale 0-100). Subjects were exposed to 4 3-month intermittent courses. | After 18 months | 
| Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL) | Quality of Life was measured using a validated uterine fibroid symptom questionnaire. Total score for health related quality of Life (HRQL) range from 0 to 100 with higher scores indicating better Quality of Life. Subjects were exposed to 4 3-month intermittent courses. | 18 months | 
| Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS) | Pain was assessed using a Visual Analogue Scale (VAS) ranging from 0 to 100 with higher score indicating more severe pain. Subjects were exposed to 4 3-month intermittent courses. | After 18 months |